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others_342_1503

Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life. © 2023 The Author(s)

10.1016/j.ejmg.2023.104770

pubmed_495_11070

A minimally invasive prostatic interstitial temperature-mapping technique is described that supplies accurate, detailed information on thermal doses delivered to precisely localized tissue sites. The technique employs a comparatively large numbers of thermosensors, highly accurate placement of those thermosensors at specified three-dimensional coordinates, fiberoptic technology that avoids significant interaction between the thermosensors and the applied microwave field, and continuous temperature readout. Biplane ultrasound imaging and fluoroscopy were used to ensure stereotactic accuracy of thermosensor placement. The technique was applied in 15 patients with benign prostatic hyperplasia (BPH) undergoing a 1-hour microwave thermal treatment session. The thermal mapping procedures and microwave treatment were generally well tolerated. The mean maximum temperature in the prostate and periprostatic tissue (57.9 +/- 1.9 degrees C) was significantly higher (P < 0.001) by more than 18 degrees C than that in either the urethra (39.6 +/- 0.9 degrees C) or the rectum (40.8 +/- 1.7 degrees C). In a representative patient, microwave treatment resulted in stable elevation of temperature 5 mm radially from the urethra that averaged 66.0 +/- 0.1 degrees C. At 10 mm from the urethra, the temperature averaged 50.5 +/- 0.1 degrees C. Urethral and rectal temperatures remained at innocuous levels. In conjunction with pathologic studies, this interstitial thermal mapping method should prove useful in defining the optimal thermal doses for microwave therapy. The method should also find uses in evaluating different microwave treatment systems, which can vary markedly in thermal performance, as well as other modalities that apply heat to prostatic tissue.

10.1089/end.1995.9.339

pubmed_248_18021

OBJECTIVE To study the clinicoepidemiologic profile of cutaneous leishmaniasis (CL) in Yemen (Hajjah and adjacent regions) and to identify the Leishmania species responsible. METHODS All 136 cases [96 (70.6%) males and 40 (29.4%) females] were subjected to detailed analysis. The diagnosis was based on positive slit skin smear and histopathologic studies when needed. In four cases, in vitro culture and Leishmania characterization by isoenzyme electrophoresis of 15 isoenzymes were attempted. RESULTS Most of the patients (107; 78.7%) were residents of the Hajjah Governorate. The majority of the patients had a single noduloulcerative lesion on the face. Slit skin smear was positive for parasites in 128 (94%) cases (highly positive in 63 cases) and four Leishmania isolates were obtained. The isoenzyme characterization results revealed L. tropica to be the species responsible, and zymodeme analysis showed that one strain belonged to zymodeme MON137, and three strains belonged to two previously undescribed zymodemes similar to zymodeme MON71. CONCLUSION CL seems to be endemic in this region. L. tropica was identified as the species responsible in four strains.

10.1111/j.1365-4632.2004.02588.x

pubmed_383_23683

Obesity remains a growing public health epidemic that has increased healthcare costs and related comorbidities. Current treatment guidelines encourage a multidisciplinary approach starting from patient selection, interventions, and long-term follow-up to maintain weight loss. However, these conservative interventions are largely ineffective at reducing body weight due to low adherence to the treatment regimen. Recently, endoscopic bariatric therapies have become an attractive alternative to traditional invasive bariatric surgeries due to their improved efficacy, safety, and cost-effectiveness. Endoscopic bariatric therapies include intragastric balloon placement, endoscopic sleeve gastroplasty, gastric bypass revision, and aspiration therapy. These procedures fall into two separate categories depending on the primary mechanism involved: restrictive or malabsorptive. Restrictive methods, such as the Orbera® and ReShape™ intragastric balloons, increase satiation and delay gastric emptying while decreasing the amount of food that can be ingested. In contrast, malabsorptive devices, such as the EndoBarrier®, interfere with the small intestine's ability to absorb food while restoring normal gastrointestinal hormone levels regulating satiation. Together, these techniques provide useful alternatives for patients in whom pharmacological or lifestyle modifications have proven ineffective. Despite these advantages, the long-term effects of these procedures on metabolic changes remain to be studied. Furthermore, the management of complications from these procedures continues to evolve. In this review, we aim to elaborate on the clinical indications and efficacy of the endobariatric procedures, together with various types of available endoscopic bariatric therapy procedures.

10.1177/2631774520984627

pubmed_56_14874

Snow can preserve the atmospheric information, which makes it become a good media in studying regional environment. Jinfo Mountain with an elevation of 2251.1 m, located at the transition zone between Sichuan basin and Yunnan-Guizhou Plateau, is deeply affected by human activities, and snowfall is the main form of precipitation during the winter. While the literature focus on single spherical particles in this area is uncommon. Five snow samples were collected, and determined morphology and chemical composition of 132 single spherical particles by the scanning electron microscope couples with energy dispersive X-ray spectrometer (SEM-EDS). Results show that snowfall in Jinfo Mountain includes the massive fly ash particles with 1.64 µm in average diameter and 1.09 in average roundness which contains smooth particles, rough particles and soot particles, accounting for 80. 31% , 14. 39% and 5.30% of statistical particles respectively. Furthermore, on the basis of chemical information obtained from EDS, the fly ash particles counted in this research can be classified into 5 types, namely, Si-dominant particles, C-dominant particles, Fe-dominant particles, Al-dominant particles and Ti-dominant particles, which make up 34.09%, 49.24%, 12.88%, 2.27% and 1.52% respectively. In conclusion, it can be inferred, based on the analysis of meteorological information, the properties of fly ash particles, and backward air mass trajectory and dispersion analysis, that C-dominant fly ash mainly comes from daily life and industry activities, Si-dominant fly ash particles may originate from the plant industry located in west Chingqing, north of Guizhou province, central of Hunan province, Zhejiang province, Jiangxi province and the west of Guangdong province, while the activities of foundry and iron or steel plants in the west of Chongqing, the north of Guizhou province and the central of Hunan province may be the main sources of Fe-dominant fly ash particles in our samples.

pubmed_56_14874

pubmed_1052_5212

The mouse methionine sulfoxide reductase A (MsrA) belongs to the subclass of MsrAs with one catalytic and two recycling Cys corresponding to Cys51, Cys198 and Cys206 in Escherichia coli MsrA, respectively. It was previously shown that in the absence of thioredoxin, the mouse and the E. coli MsrAs, which reduce two mol of methionine-O substrate per mol of enzyme, displays an in vitro S-stereospecific methionine oxidase activity. In the present study carried out with E. coli MsrA, kinetic evidence are presented which show that formation of the second mol of Ac-L-Met-NHMe is rate-limiting in the absence of thioredoxin. In the presence of thioredoxin, the overall rate-limiting step is associated with the thioredoxin-recycling process. Kinetic arguments are presented which support the accumulation of the E. coli MsrA under Cys51 sulfenic acid state in the presence of Trx. Thus, the methionine oxidase activity could be operative in vivo without the action of a regulatory protein in order to block the action of Trx as previously proposed.

pubmed_1052_5212

pubmed_126_11768

Although NFkappaB binding activity is induced during liver regeneration after partial hepatectomy, the physiological consequence of this induction is unknown. We have assessed the role of NFkappaB during liver regeneration by delivering to the liver a superrepressor of NFkappaB activity using an adenoviral vector expressing a mutated form of IkappaBalpha. This adenovirus (Ad5IkappaB) was almost exclusively expressed in the liver and inhibited NFkappaB DNA binding activity and transcriptional activity in cultured cells as well as in the liver in vivo. After partial hepatectomy, infection with Ad5IkappaB, but not a control adenovirus (Ad5LacZ), resulted in the induction of massive apoptosis and hepatocytes as demonstrated by histological staining and TUNEL analysis. In addition, infection with Ad5IkappaB but not Ad5LacZ decreased the mitotic index after partial hepatectomy. These two phenomena, increased apoptosis and failure to progress through the cell cycle, were associated with liver dysfunction in animals infected with the Ad5IkappaB but not Ad5LacZ, as demonstrated by elevated serum bilirubin and ammonia levels. Thus, the induction of NFkappaB during liver regeneration after partial hepatectomy appears to be a required event to prevent apoptosis and to allow for normal cell cycle progression.

10.1172/JCI483

pubmed_60_5582

BACKGROUND Many hospitals have adopted smoke-free policies on their property. We examined the consequences of such polices at two Canadian tertiary acute-care hospitals. METHODS We conducted a qualitative study using ethnographic techniques over a six-month period. Participants (n=186) shared their perspectives on and experiences with tobacco dependence and managing the use of tobacco, as well as their impressions of the smoke-free policy. We interviewed inpatients individually from eight wards (n=82), key policy-makers (n=9) and support staff (n=14) and held 16 focus groups with health care providers and ward staff (n=81). We also reviewed ward documents relating to tobacco dependence and looked at smoking-related activities on hospital property. RESULTS Noncompliance with the policy and exposure to secondhand smoke were ongoing concerns. Peoples' impressions of the use of tobacco varied, including divergent opinions as to whether such use was a bad habit or an addiction. Treatment for tobacco dependence and the management of symptoms of withdrawal were offered inconsistently. Participants voiced concerns over patient safety and leaving the ward to smoke. INTERPRETATION Policies mandating smoke-free hospital property have important consequences beyond noncompliance, including concerns over patient safety and disruptions to care. Without adequately available and accessible support for withdrawal from tobacco, patients will continue to face personal risk when they leave hospital property to smoke.

10.1503/cmaj.110235

others_373_2000

The kiwifruit brand Sanuki Kiwicco® comprises five kiwifruit cultivars (KagawaUP-Ki1, −2, −3, −4, and − 5) that are hybrids of Actinidia chinensis and Actinidia rufa, have high quality, small fruits with a sugar content of 17 to 20% and a low level of protease, thus eliminating any mouth irritation. The cultivars of Sanuki Kiwicco® are more tolerant to bacterial blossom blight and can be stored longer than previously released cultivar Kosui, another hybrid between A. chinensis and A. rufa. Our investigations using A. rufa, a wild species in warm regions of Japan, revealed efficient transduction of tolerance to bacterial canker disease caused by Pseudomonas syringae pv. actinidiae biovar 3. The Sanuki Kiwicco® cultivars also proved to have practical tolerance to the disease caused by biovar 3 in laboratory and field tests. © 2019, Società Italiana di Patologia Vegetale (S.I.Pa.V.)

10.1007/s42161-019-00349-9

pubmed_628_3103

1,1-Dimethylpropyl hydroperoxide reacts with cobalt(II) cobinamide via a Fenton-like reaction to produce a mixture of the diastereomeric alpha- and beta-ethylcobinamides (CH(3)CH(2)Cbi(+)'s, in which the organic ligand is in the "lower" or "upper" axial ligand position, respectively), the composition of which depends on the ratio of starting materials. When the hydroperoxide reagent is in excess, <2% of the CH(3)CH(2)Cbi(+) product is the alpha diastereomer, a product distribution which agrees with previous observations of the equilibrium mixture. This distribution apparently arises because the previously demonstrated CH(3)CH(2)(*)-promoted isomerization of CH(3)CH(2)Cbi(+) diastereomers leads to equilibration. However, when cob(II)inamide is in excess over hydroperoxide, the CH(3)CH(2)Cbi(+) product contains 87% alpha diastereomer and 13% beta diastereomer. Evidently, under these conditions, trapping of the CH(3)CH(2)(*) radical is sufficiently rapid to prevent the radical-induced isomerization of diastereomers and a kinetically controlled product distribution results. This condition has been used to study the relative energetics of kinetically controlled alpha and beta alkylation of cob(II)inamide by CH(3)CH(2)(*). For cob(II)inamide itself, the alpha diastereomer is enthalpically stabilized relative to the beta diastereomer in the transition state for carbon-cobalt bond formation, but an even larger entropic stabilization of the beta diastereomer causes the latter to be the predominant product. The entropic preference for the beta diastereomer is shown to be the result of the differential side chain configurations at the alpha and beta faces of the cobalt corrinoids by experiments with side-chain-altered analogs. When the downwardly projecting f side chain is enlarged by esterification of the N-methylated nucleotide 1-alpha-D-ribofuranosyl-3,5,6-trimethylbenzimidazole 3'-phosphate, the proportion of the alpha diastereomer in the alkylated product drops to 74% and the effect is due solely to an increased entropic preference for the beta diastereomer. Similarly, when the normally downwardly projecting e propionamide side chain is epimerized to the upward (beta) face of the corrin, the proportion of the alpha diastereomer in the product is increased to 95% and the effect is entirely entropic again. Taken together with previous work, the results lead to a general picture of the energetics of alkyl radical + cobalt(II) corrinoid combination reactions and their microscopic reverse, the homolytic dissociation of carbon-cobalt bonds, a rare instance in which the subtleties of such diastereomeric control can be understood at a very fundamental level.

10.1021/ic9614273

pubmed_634_155

We report a base-promoted metal-free approach for the synthesis of thieno[2,3-b]indole derivatives. This method combined four C-H σ-bond cleavage reactions of two different kinds of C-H bonds and two C-S σ-bond formation processes. A series of thieno[2,3-b]indoles were obtained starting from 3-benzylindole derivatives with good yields and high regioselectivity, with the elemental sulfur serving as a cheap and readily available sulfur source. Good efficiency could be maintained even when the reaction was performed on a gram scale. A plausible mechanism was proposed on the basis of mechanistic studies.

10.1021/acs.joc.9b01586

pubmed_639_21623

BACKGROUND The anatomical resection of Segment 3 and 4 of the liver under conventional laparotomy was reported [1]. We present the laparoscopic approach for this type of resection. METHOD Laparoscopic left ventral hepatic segmentectomy [2] including the Segment 3 (S3) and the ventral Segment 4 (S4v), preserving the Segment 2 (S2) and the dorsal Segment 4 (S4d), was performed for the hepatocellular carcinoma located at the root of the Glissonean pedicle of the S3. VIDEO After the pneumoperitoneum and the mobilization of the left lateral segment, the Glissonean pedicle for the left ventral segment was controlled and occluded. The demarcation line between the left ventral segment and the Segment 2 (S2), the dorsal Segment 4 (S4d) and the Segment 5 (S5) was confirmed using indocyanine green-fluorescence imaging [3]. The hepatic parenchymal resection was started along the demarcation line between the S3 and S2 on the dorsal lateral segment [4], followed by the division of the Glissonean pedicle of the left ventral segment. Further parenchymal division between the S4v and S4d, and that between the S4v and S5 resulted in the completion of the laparoscopic left ventral hepatic segmentectomy. RESULTS The operative time was 221 minutes and the intraoperative blood loss was 10 ml. The postoperative course was uneventful and the patient was discharged 7days after the surgery. CONCLUSIONS The left ventral hepatic segmentectomy could be among the standard choices of laparoscopic anatomical resection for a tumor located around the top of the umbilical portion in selected HBP institutes.

10.1016/j.suronc.2021.101571

pubmed_42_4707

Some undesirable effects are associated with chronic estrogen and progestin administration used to prevent bone loss in postmenopausal women, thus leading to poor compliance and the need for improved therapeutic and preventive agents. We have thus studied the ability of the new antiestrogen EM-800 (SCH 57050) to prevent bone loss and lower serum cholesterol levels and compared its effects with those of raloxifene. Ovariectomized (OVX) female rats were treated by oral gavage for 37 weeks with increasing daily doses (0.01, 0.03, 0.1, 0. 3 or 1 mg/kg) of EM-800 or raloxifene. At 35 weeks after OVX, lumbar spine bone mineral density (BMD) was 19% lower than in intact animals (P<0.01), while the OVX animals given EM-800 or raloxifene had 90-93 and 85-90%, respectively, of the BMD values observed in intact rats. Similar effects were observed on femoral BMD. Bone histomorphometry measurements were performed on proximal tibia. At the 0.01 mg/kg dose, EM-800 prevented the effect of OVX on TBV by 34% (P<0.01), while raloxifene had no detectable effect. Treatment with 1 mg/kg EM-800 and raloxifene resulted in, respectively, 68% (P<0.01) and 64% (P<0.01) prevention of the OVX-induced decrease in TBV. In addition, the administration of 0.01 and 0.03 mg/kg EM-800 caused, respectively, 54% (P<0.01) and 56% (P<0.01) inhibitions of serum cholesterol levels, while raloxifene administered at the same doses caused, respectively, 24% (P<0.01) and 41% (P<0.01) decreases of the value of the same parameter. At the highest doses used (0.1-1 mg/kg), both compounds lowered serum cholesterol levels by approximately 65% (P<0.01). No stimulatory effect of EM-800 was observed on the endometrial epithelial cells at doses up to 1 mg/kg, while hypertrophy of uterine epithelium was observed with raloxifene. EM-800 and raloxifene achieve the same degree of effectiveness on bone and serum cholesterol at higher doses, but EM-800 is at least three to ten times more potent than raloxifene at lower concentrations and has no stimulatory effect on uterine epithelium. The present data show the potent effect of EM-800 preventing bone loss and lower serum cholesterol levels without the negative effect on the endometrium, thus suggesting the particular interest of this new fully tissue-specific selective estrogen receptor modulator.

10.1016/s0960-0760(00)00087-x

pubmed_1015_2161

We conducted an epidemiological and etiological study of softball injuries to the hand in order to inform emergency medicine personnel of the high frequency and causative factors of these injuries. Injuries to the hand and fingers from baseball and softball comprised 2.2% of emergency department visits during this study. Most frequent injuries were: 1) sprain and sprain-fracture of the proximal IP joint (31.6%); and 2) the so-called "mallet" or "baseball finger" injury to the distal joint (18.9%). The 16-inch softball was the cause of more than two-thirds of all these injuries, most of which occurred in patients between the ages of 11 and 30. Treatment recommendations are beyond the scope of this article.

10.1016/s0196-0644(81)80120-5

pubmed_649_20600

Analysis of the data of 2.762 infants with "unidentified" (i.e., no identified as dysmorphological entities) multiple congenital abnormalities from the Hungarian Congenital Malformation Registry, 1970-1976 showed that the majority of congenital abnormalities in newborns with multiple congenital abnormalities was not due to random combinations. The ratio of expected random combination and observed causal effect was 1: 6, 1: 225-1: 14,000 and 1: 2.10(6) in two, three, four, and five or more congenital abnormalities, respectively. Our multidimensional threshold model supposes specified liabilities for each congenital abnormality, and the correlation structure of these liabilities explains nearly all associations of congenital abnormalities in unidentified multiple congenital abnormalities. According to this hypothesis, the expected and the observed occurrences do not differ significantly either in the sum or in the various possible threefold associations of congenital abnormalities. The biological reasons for the phenomenon are being studied.

pubmed_649_20600

pubmed_796_9438

Intramolecular electron transfer in partially reduced cytochrome c oxidase has been studied by the perturbed equilibrium method. We have prepared a three-electron-reduced, CO-inhibited form of the enzyme in which cytochrome a and copper A are partially reduced and in an intramolecular redox equilibrium. When these samples were irradiated with a nitrogen laser (0.6-ns, 1.0-mJ pulses) to photodissociate the bound CO, changes in absorbance at 598 and 830 nm were observed which were consistent with a fast electron transfer from cytochrome a to copper A. The absorbance changes at 598 nm gave an apparent rate of 17,000 +/- 2000 s-1 (1 sigma), at pH 7.0 and 25.5 degrees C. These changes were not observed in either the CO mixed-valence or the CO-inhibited fully reduced forms of the enzyme. The rate was fastest at about pH 8.0, falling off toward both lower and higher pHs. There was a small but clear temperature dependence. The process was also observed in the cytochrome c-cytochrome c oxidase high-affinity complex. The electron equilibration measured between cytochrome a and copper A is far faster than any rate measured or inferred previously for this process.

10.1021/bi00443a030

pubmed_445_13755

Features of propagation of 4 herpes simplex virus strains and their biological properties in the course of passages in chick embryo fibroblast cultures were studied. Investigations of experimental formalin-inactivated polyvaccine in animals and in trials in volunteers, patients with relapsing herpes, established its safety and sufficient effectiveness.

pubmed_445_13755

pubmed_495_16632

Streptomyces erythraeus produces an extracellular mammalian-type serine protease bearing trypsin-like substrate specificity. The gene encoding the protease was cloned and sequenced as an initial step for investigating its structure-function relationship by site-specific mutagenesis. The cloned gene is composed of an 816-bp open reading frame encoding 272 amino acid residues, suggesting that it is synthesized as a precursor protein containing a 42-residue prepropeptide. In the N-terminal prepropeptide portion, the tract of 30 residues from the initiator methionine has a typical signal sequence for Streptomyces and the remaining 12 residues are thought to comprise a propeptide. The cloned gene was replaced downstream of a strong promoter in a high expression plasmid, pSEV2, and expressed in Streptomyces lividans TK24. The gene product was secreted extracellularly and identified as an inactive precursor which consists of the mature enzyme and the 12-residue N-terminally extended peptide chain. The precursor protein was converted to a fully active mature form by limited proteolysis with alpha-chymotrypsin at the Phe-(-1)-Ile-1 bond. Protein sequence analysis revealed that, except for the C-terminal three residues, recombinant SET is identical with the native enzyme.

10.1093/oxfordjournals.jbchem.a124912

pubmed_774_21148

Following publication of the original article [1], the authors reported that one of the authors' names is spelled incorrectly.

10.1186/s12911-019-0802-3

pubmed_844_15337

'Smart drugs' are drugs supposed to enhance certain physical or mental functions, without harmful side effects. The target group for the misleading advertisement campaigns on the Net is mostly the younger generation. Smart drugs clearly are pharmacologically active: phenytoin, selegilin and growth hormone are examples of compounds that can be ordered from mail order pharmacies without prescription. Misleading medical information on the Internet is undesirable and potentially harmful and the widespread availability of smart drugs should be realised by pharmacists and physicians. Screening the Net for this kind of information should be implemented as a standard procedure and specific, targeted information to put these drugs in a realistic perspective could be the first step leading to 'debunking' the Internet.

pubmed_844_15337

pubmed_373_5626

Open complex formation precedes initiation of transcription by RNA polymerases. In the analysis of transcription initiation from eukaryotic class II promoters, we have used promoter DNA structures that represent intermediates in open complex formation. We describe the preparation and isolation of heteroduplex promoter fragments. Probes containing these DNA structures have a general application in the study of proteins binding to junctions of double- and single-stranded DNA. Such proteins play important roles not only in the regulation of RNA synthesis but also in processes like repair, replication, and recombination of DNA. In addition, a protocol is provided for a rapid and quantitative assay for open complexes and transcription bubbles using potassium permanganate as a chemical probe for single-stranded regions in DNA.

10.1006/meth.1997.0472

pubmed_302_9738

Impaired postnatal growth in very low birth weight (VLBW, <1500 g) infants is per se a major clinical challenge and may also serve as a model in studying the mechanisms of growth retardation in general. This study was undertaken to characterize the role of IGFs and their binding proteins (IGFBPs), key regulators of fetal and infant growth, during the postnatal period in VLBW infants. Forty-eight VLBW infants (gestational age 27.6 +/- 2.2 wk, birth weight 923 +/- 257 g) were studied. Blood samples were drawn at 1, 2, 4, and 8 wk of age for measurements of IGF-I, IGFBP-1 (lesser phosphorylated, lpIGFBP-1, and highly phosphorylated, hpIGFBP-1), IGFBP-3, and insulin, simultaneous growth velocities being assessed by a rigorous protocol of repeated, frequent lower leg length and body weight measurements. All regression analyses were adjusted for postnatal age and repeated measurements. Lower leg growth velocity showed a positive correlation with IGF-I (P = 0.01) and IGFBP-3 (P = 0.03), and weight growth velocity with IGFBP-3 (P = 0.057) and with lpIGFBP-1/hpIGFBP-1 ratio (P = 0.01). Moreover, concurrent glucocorticoid dose showed a negative correlation with both IGFBP-1 isoforms, observable, however, only in samples with high (>10 U/liter) insulin (lpIGFBP-1, P = 0.02; hpIGFBP-1, P = 0.007). In backward multiple regression analysis, the factor remaining significantly associated with lower leg growth velocity (R(2) = 0.63) was IGF-I, and factors associated with weight growth velocity (R(2) = 0.81) were IGFBP-3 and the lpIGFBP-1/hpIGFBP-1 ratio. In conclusion, circulating IGF-I and IGFBP-3, and the lpIGFBP-1/hpIGFBP-1 ratio, reflect short-term growth velocity in VLBW infants. lpIGFBP-1 isoforms, abundant in the circulation of these infants, may thus also have properties that are at least less inhibitory, if not promoting, on the growth-stimulating action of IGF-I. Finally, the regulation of IGFBP-1 by glucocorticoids may be divergent in situations with a high or low insulin concentration.

10.1210/jcem.87.5.8457

pubmed_689_10035

Neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analysed transcriptomic data from AD and PD patients, and stratified these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identified retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrated that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.

10.3390/biomedicines9101310

pubmed_256_21437

The present study examined the effect of GnRH pulse amplitude on alpha, LH beta and FSH beta mRNAs using an in vitro perfusion model. Pituitaries from 30-day-old female rats were dissociated and the cells plated for 48 h to allow attachment to collagen-coated microcarrier beads. The beads were loaded into perifusion chambers, preperifused for 1 h, and then given GnRH pulses (17.5-175 pg/ml) every 30 min for 24 h. Perifusate LH was measured after 2 h and 22 h of perifusion and alpha LH and FSH beta messenger RNAs (mRNAs) were determined by hybridization to complementary DNA (cDNA) probes. All doses of GnRH acutely stimulated LH release, and responses were similar after 2 h and 22 h. LH release increased as a function of GnRH pulse dose with maximal increases seen following 70 pg/ml pulses. alpha mRNA levels (control = 0.73 +/- 0.1 fmol cDNA bound/100 micrograms pituitary DNA) were increased 30% and 40% after 24 h of 35 and 70 pg/ml pulses, respectively (P < 0.05 vs. media controls). LH beta mRNA concentrations (control = 0.44 +/- 0.08 fmol cDNA bound) were only elevated after 35 pg/ml GnRH pulses (36% increase). FSH beta mRNA showed the largest responses to GnRH pulses, increasing by 45% and 84% after 35 and 70 pg pulses, respectively (control = 0.14 +/- 0.02 fmol bound). The highest GnRH pulse dose (175 pg/ml) was ineffective in stimulating an increase in FSH beta mRNA levels. These results show that all three gonadotropin subunit mRNA concentrations increase after 24 h of GnRH pulses, but the pattern of individual subunit mRNA responses was dependent upon the amplitude of the GnRH pulse stimulus. These data support earlier results in vivo, in that the subunit responses to GnRH pulse dose were similar. Thus, alterations in the amplitude of pulsatile GnRH secretion from the median eminence may be one mechanism by which the expression of gonadotropin subunit genes are regulated.

10.1210/endo.132.3.7679975

pubmed_347_11887

BACKGROUND Medically unexplained symptoms (MUS) are common in primary care across cultures, accounting for high consultations with multiple providers and unnecessary investigations. Cognitive behavioural therapy (CBT) is efficacious for MUS and reduces physical symptoms, psychological distress and disability. Two intervention trials by the author and his group remain the only reported trials from the developing world. MATERIAL A treatment package was designed by modifying a CBT model. The modifications were innovative use of locally relevant appropriate language and strategies that were simple enough while conforming to the CBT principles. The aim was to convey the principles of CBT to people using simple techniques--using metaphor. These are described in the paper as generic metaphors that could be used to explain the CBT principles and specific ones for patients with MUS. DISCUSSION Metaphor is an effective clinical tool. The author's clinical experience and patients' feedback suggest that these metaphors are helpful in conveying the CBT principles to patients. To develop metaphors appealing to the client and effective clinically, carrying out qualitative research among patients' explanatory model is an important prerequisite. The generic and MUS-specific metaphors reported here should be tried in other cultural and clinical settings and evaluated. Further systematic work including qualitative work for consensus evaluation among CBT experts as well as opinion on user-friendliness of these techniques tested among CBT practitioners will be needed.

10.1177/0020764012467897

pubmed_149_24210

The concept of "disease modification" refers to an intervention that modifies the natural clinical course of the disease along with improvement of symptoms. With regard to this, providing treatment that improves clinical signs and symptoms of axial spondyloarthritis (axSpA) and that impacts disease pathogenesis by slowing/halting bone formation is the main goal of this concept. It has been proven that currently available treatments including biologics and nonsteroidal anti-inflammatory drugs have a symptom-modifying effect in axSpA. The body of evidence showing a beneficial effect of biologic therapy on spinal damage is growing. In this article, by centralizing new bone formation as a main target of disease modification, we reviewed molecular mechanisms related to new bone formation, relevance of imaging studies on assessment of disease progression, clinical predictors of new bone formation, and disease-modifying properties of currently available treatments in axSpA.

10.1016/j.berh.2019.02.007

pubmed_781_14644

BACKGROUND The physiological uptake of 18F-fluorodeoxyglucose (FDG) in the heart often interferes with the accurate diagnosis of inflammatory cardiac diseases (CDs). Unfractionated heparin (UFH) administration may suppress its uptake through the alteration of myocardial metabolism. PURPOSE To clarify the effectiveness of UFH administration to suppress the physiological FDG uptake in the heart. MATERIAL AND METHODS The physiological FDG uptake in the heart was compared among 178 patients who fasted less than 18 h, 37 patients who fasted more than 18 h, and 64 patients who fasted more than 18 h and were administered UFH (UFH-CD group) prior to FDG PET/CT. Free fatty acid (FFA), triglyceride, insulin, and blood glucose levels were measured after UFH administration. Myocardial FDG uptake was evaluated by visual assessment and on the basis of maximum standardized uptake value (SUVmax). RESULTS In the UFH-CD group, the FFA level increased 15 min after UFH administration (P < 0.01). Blood glucose and insulin levels remained unchanged (P = NS). FDG physiological uptake was observed in 69% of the patients who fasted less than 18 h, 38% of the patients fasted more than 18 h, and 22% of the UFH-CD group (P < 0.01 for trend). SUVmax decreased in the UFH-CD group compared with the patients who fasted less than 18 h (P < 0.01) and the patients who fasted more than 18 h (P = 0.029). CONCLUSION UFH administration and fasting more than 18 h could effectively suppress FDG physiological uptake in the heart and can be a useful method of detecting inflammatory CDs and tumors.

10.1177/0284185115600916

pubmed_849_17190

BACKGROUND The relationships between lncRNAs and tumors have currently become one of the focuses on cancer studies. However, there are a few studies about lncRNAs in non-small cell lung cancer (NSCLC) at present. METHODS Microarray analysis was designed to study the expression patterns of lncRNAs in three pairs of NSCLC tissues. The expression of lncRNA RGMB-AS1 and repulsive guidance molecule b (RGMB) were detected in 72 paired NSCLC tissues and adjacent normal tissues by qRT-PCR assay. The relations of lncRNA RGMB-AS1 and RGMB expression with clinicopathological factors of NSCLC patients were explored. A549 and SPC-A-1 cells were transfected with siRNA of lncRNA RGMB-AS1 and negative control. RGMB expression level was detected by qRT-PCR assay and western blot analysis. RESULTS The results of microarray found that 571 lncRNAs were differentially expressed in NSCLC tissues (Fold change cut-off: 5.0, P < 0.05), including 304 upregulated and 267 downregulated lncRNAs. The results of qRT-PCR showed that lncRNA RGMB-AS1 expression was significantly higher in NSCLC tissues than in adjacent normal tissues (P < 0.05), while RGMB mRNA showed an opposite trend (P < 0.05). Correlation analysis indicated that the expression of lncRNA RGMB-AS1and RGMB mRNA were inversely correlated (R(2) = 0.590, P < 0.05). While lncRNA RGMB-AS1 and RGMB expression levels in NSCLC tissues were associated with the occurrence of differentiation status, lymph node metastases and TNM stage (P < 0.05). Transfection with siRNA of lncRNA RGMB-AS1, subsequent results showed that RGMB mRNA and protein expression were upregulated (P < 0.05) in A549 and SPC-A-1 cells compared to the control groups. CONCLUSION We identified lncRNA RGMB-AS1 was upregulated and RGMB was downregulated in NSCLC patients. Both were related to differentiation status, lymph node metastases and TNM stage. Studies also indicated that lncRNA RGMB-AS1and RGMB were inversely correlated. VIRTUAL SLIDES The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7911587521528276.

10.1186/s13000-015-0297-x

pubmed_78_103

The structure of a closely integrated data warehouse is described that is designed to link different types and varying numbers of biological networks, sequence analysis methods and experimental results such as those coming from microarrays. The data schema is inspired by a combination of graph based methods and generalised data structures and makes use of ontologies and meta-data. The core idea is to consider and store biological networks as graphs, and to use generalised data structures (GDS) for the storage of further relevant information. This is possible because many biological networks can be stored as graphs: protein interactions, signal transduction networks, metabolic pathways, gene regulatory networks etc. Nodes in biological graphs represent entities such as promoters, proteins, genes and transcripts whereas the edges of such graphs specify how the nodes are related. The semantics of the nodes and edges are defined using ontologies of node and relation types. Besides generic attributes that most biological entities possess (name, attribute description), further information is stored using generalised data structures. By directly linking to underlying sequences (exons, introns, promoters, amino acid sequences) in a systematic way, close interoperability to sequence analysis methods can be achieved. This approach allows us to store, query and update a wide variety of biological information in a way that is semantically compact without requiring changes at the database schema level when new kinds of biological information is added. We describe how this datawarehouse is being implemented by extending the text-mining framework ONDEX to link, support and complement different bioinformatics applications and research activities such as microarray analysis, sequence analysis and modelling/simulation of biological systems. The system is developed under the GPL license and can be downloaded from http://sourceforge.net/projects/ondex/

pubmed_78_103

pubmed_442_12629

BACKGROUND Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral adenosine triphosphate-competitive AURKA inhibitor. PATIENTS AND METHODS This Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii) leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i.d. d1-d7 every 21 days. The primary end point was response rate; progression-free survival (PFS) was secondary. One response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon two-stage design. RESULTS Seventy-two patients were enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4% were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other sarcoma cohort. The histology-specific cohorts ceased at the first stage. There were two confirmed PRs in the other cohort (both angiosarcoma) and one unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-week PFS was 73% (LPS), 44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%), and neutropenia (42%). CONCLUSIONS Alisertib was well tolerated. Occasional responses, yet prolonged stable disease, were observed. Although failing to meet the primary RR end point, PFS was promising. TRIAL REGISTRATION ID NCT01653028.

10.1093/annonc/mdw281

pubmed_94_16716

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Increasingly evidences indicate that extracellular vesicles (EVs) orchestrate multiple processes in tumorigenesis, metastasis, immune evasion, and drug response of RCC. EVs are lipid membrane-bound vesicles in nanometer size and secreted by almost all cell types into the extracellular milieu. A myriad of bioactive molecules such as RNA, DNA, protein, and lipid are able to be delivered via EVs for the intercellular communication. Hence, the abundant content of EVs is appealing reservoir for biomarker identification through computational analysis and experimental validation. EVs with excellent biocompatibility and biodistribution are natural platforms that can be engineered to offer achievable drug delivery strategies for RCC therapies. Moreover, the multifaceted roles of EVs in RCC progression also provide substantial targets and facilitate EVs-based drug discovery, which will be accelerated by using artificial intelligence approaches. In this review, we summarized the vital roles of EVs in occurrence, metastasis, immune evasion, and drug resistance of RCC. Furthermore, we also recapitulated and prospected the EVs-based potential applications in RCC, including biomarker identification, drug vehicle development as well as drug target discovery.

10.3389/fonc.2020.00724

pubmed_810_1800

BACKGROUND Interactions between the serotonergic system and the hypothalamic-pituitary-adrenal axis have been suggested, albeit the details for such interactions have yet to be established. Animal studies have shown that the density of serotonin 5-HT2A receptors is increased after administration of exogenous glucocorticoids. OBJECTIVE The objective of this study was to explore possible changes in the pattern of density and affinity of 5-HT2A receptors in humans after treatment with glucocorticoids. METHODS Using a radioactive binding assay, the density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin receptors were measured in blood samples drawn from 27 individuals diagnosed with polymyalgia rheumatica and/or giant cell arteritis before and after start of an oral treatment with prednisolone. For each patient Bmax and Kd at baseline before prednisolone treatment were compared with Bmax and Kd in samples drawn at a first and second follow-up clinic visit at an average of 8.8 (±2.5) days and 33.6 (±6.8) days, respectively. RESULTS The density of 5-HT2A receptors increased after treatment in 23 individuals. The mean Bmax value at baseline for all patients was 45.2 fmol/mg protein compared with 64.9 fmol/mg protein in the corresponding samples drawn at the second follow-up visit (p=0.001). There also was an association between individuals accumulated prednisolone dose and the magnitude of change in Bmax between baseline and the first follow-up visit. Erythrocyte sedimentation rate, platelet count or gender had no influence on the results. There were no significant differences in Kd during the treatment period. However, a low Kd value at baseline was a predictor for an increase in Bmax following treatment. CONCLUSIONS The results of this study showed that the density of 5-HT2A serotonin receptors in man is increased after a subchronic treatment with glucocorticoids. The magnitude of the increase appears to be associated with the affinity of 5-HT2A receptors before treatment and the accumulated dose of glucocorticoid early in the treatment period.

pubmed_810_1800

pubmed_603_10496

The type A behavior pattern (TABP) was described in the 1950s by cardiologists Meyer Friedman and Ray Rosenman, who argued that TABP was an important risk factor for coronary heart disease. This theory was supported by positive findings from the Western Collaborative Group Study and the Framingham Study. We analyzed tobacco industry documents to show that the tobacco industry was a major funder of TABP research, with selected results used to counter concerns regarding tobacco and health. Our findings also help explain inconsistencies in the findings of epidemiological studies of TABP, in particular the phenomenon of initially promising results followed by negative findings. Our analysis suggests that these "decline effects" are partly explained by tobacco industry involvement in TABP research.

10.2105/AJPH.2012.300816

pubmed_325_7401

OBJECTIVE The aim of this study was to investigate the relationship between the NEC and TOF-PET image quality. METHODS The National Electrical Manufactures Association and International Electrical Commission (NEMA IEC) body phantom with a 10-mm diameter sphere was filled with an 18F-FDG solution with a 4:1 radioactivity ratio. The PET data were acquired in the three-dimensional list mode for 20 min. We created frame data ranging from 1 to 5 min acquisition time, which were then reconstructed using the baseline ordered-subsets expectation maximization (OSEM), the OSEM + point spread function (PSF) algorithm, OSEM + time-of-flight (TOF) algorithm and OSEM + PSF + TOF algorithm. The PET images were analyzed according to the noise-equivalent count (NEC), the coefficients of variance of the background (CVBG), the maximum count (CVmax) and the contrast (CVCONT). The results were compared with the recommended value according to the guidelines for the oncology FDG-PET/CT protocol. RESULTS The NEC was higher than the recommended value at 3 min or longer acquisition time. The CVBG lower than 15% were obtained at 3 min acquisition time without TOF and at 2 min acquisition time with TOF. The CVBG of 10% or lower were obtained at 5 min or longer acquisition time without TOF and at 4 min or longer acquisition time with TOF. Both the CVmax and CVCONT lower than 10% were obtained at 3 min or longer acquisition time without TOF and at 1 min acquisition or longer with TOF. No particular relationships were observed between the frame number and degree of the variation in the image quality. The CVCONT significantly correlated with the NEC for the data reconstructed without TOF information, while there were no significant correlations between these useful metrics for the data reconstructed with TOF. CONCLUSION This study demonstrated that the NEC is not a useful metric for the evaluation of the image quality on TOF-PET images.

10.1007/s12149-015-1032-0

pubmed_1004_13135

Fatty acid-binding proteins (FABPs) belong to a multigene family of small intracellular proteins that bind hydrophobic ligands. Recent studies have indicated that FABP7 plays important roles in neurogenesis or neuronal migration in vertebrates. In this study, we isolated cDNA and the genomic fragment containing the fabp7 gene for medaka fish and examined the expression of the medaka fabp7 gene through the development of their central nervous system (CNS). The medaka fabp7 gene consists of four exons in approximately 1 kb of the genomic region. Its deduced amino acid sequence exhibits over 80% identity with those of other higher vertebrates. In situ hybridization analysis demonstrated that fabp7-positive cells first appear at stage 22 in a small dorsal domain of the retina, dorsal diencephalon, and rhombencephalon, then expand to the entire CNS including the retina and the spinal cord. In addition, we generated two lines of transgenic medaka with 1.7 kb upstream of the fabp7 gene combined with the enhanced-green fluorescence protein (EGFP) gene. The spatio-temporal expression patterns of EGFP in these animals were consistent with the results of in situ hybridization analysis. The result of our reporter assays with a series of truncated fabp7 promoters suggested that POU elements play a role in fabp7 expression in medaka as well as in other vertebrates. Our transgenic animal will contribute to clarifying the role of FABP7 in the development of CNS.

10.1002/jez.b.21226

pubmed_834_10730

This study examined student's exposure to volatile organic compounds (VOCs) while commuting by bus and motorcycle in Taipei, Taiwan in the winter of 1992. A total of 19 target C5-C10 VOCs on three most frequently used commuting routes were collected on Tenax-GC adsorbent tubes. The VOCs were desorbed by thermal desorption method and analyzed by GC-MS. The most abundant VOC exposure experienced by commuters was to toluene. Several alkylated benzenes, such as propyl benzenes, ethyl-methyl-benzenes and trimethyl-benzenes, were relatively abundant on the roads in Taipei. The mean benzene concentration measured in buses was 173 micrograms/m3 and motorcycles. On the average, the commuters in Taipei experienced about three to eight times higher VOC concentrations than the commuters in Los Angeles, California. Higher VOC concentrations were measured on motorcycles than in buses. The VOC concentrations were not significantly different between morning and afternoon commutes, nor among the three commuting routes. VOC concentrations measured in classroom at three schools in downtown Taipei did not vary significantly on each sampling day. However, at each school the in-classroom VOC concentrations varied significantly over the six consecutive sampling days. The VOC concentrations measured on the roads were about five times higher than those measured in the school classrooms in the city. Moderate to high correlations were found among most of the measurements of the 19 VOCs. The survey questionnaire indicated that daily commuting time ranged from 45 minutes for elementary school students to 95 minutes for vocational school students.(ABSTRACT TRUNCATED AT 250 WORDS)

10.1080/1073161x.1993.10467200

pubmed_1047_8434

The activity of a base analog (6-N-hydroxylaminopurine, HAP) has been tested on Aspergillus nidulans. In germinating haploid conidia HAP is a strong mutagen, while it does not have any activity in resting conidia. Moreover, HAP does not increase the frequency of recombination in germinating conidia. The mutagenic activity of this base analog has also been tested in diploid conidia of A. nidulans; in fact, it has been shown (Pavlov et al., 1991) that the HAP-induced frequency of heteroallelic recessive mutations in diploid cells of the yeast S. cerevisiae is higher than expected. In A. nidulans, we did not observe any increase in the frequency of recessive homozygous fpaA/fpaA (p-fluorophenylalanine-resistant) mutants over the expected one, which has been calculated on the basis of the observed mutation frequency in the haploid strain.

10.1016/0165-1218(94)90116-3

pubmed_364_20775

Human blood platelets are non-nucleated fragments of megakaryocytes and of high importance for early hemostasis. To form a blood clot, platelets adhere to the blood vessel wall, spread and attract other platelets. Despite the importance for biomedicine, the exact mechanism of platelet spreading and adhesion to surfaces remains elusive. Here, we employ metal-induced energy transfer (MIET) imaging with a leaflet-specific fluorescent membrane probe to quantitatively determine, with nanometer resolution and in a time-resolved manner, the height profile of the basal and the apical platelet membrane above a rigid substrate during platelet spreading. We observe areas, where the platelet membrane approaches the substrate particularly closely and these areas are stable on a time scale of minutes. Time-resolved MIET measurements reveal distinct behaviors of the outermost rim and the central part of the platelets, respectively. Our findings quantify platelet adhesion and spreading and improve our understanding of early steps in blood clotting. Furthermore, the results of this study demonstrate the potential of MIET for simultaneous imaging of two close-by membranes and thus three-dimensional reconstruction of the cell shape.

10.1039/d0nr05611a

pubmed_150_24241

We surveyed 15 lakes during the growing season of 2014 in Arctic lakes of southwest Greenland to determine which factors influence methane concentrations in these systems. Methane averaged 2.5 μmol L-1 in lakes, but varied a great deal across the landscape with lakes on older landscapes farther from the ice sheet margin having some of the highest values of methane reported in lakes in the northern hemisphere (125 μmol L-1). The most important factors influencing methane in Greenland lakes included ionic composition (SO4, Na, Cl) and chlorophyll a in the water column. DOC concentrations were also related to methane, but the short length of the study likely underestimated the influence and timing of DOC on methane concentrations in the region. Atmospheric methane concentrations are increasing globally, with freshwater ecosystems in northern latitudes continuing to serve as potentially large sources in the future. Much less is known about how freshwater lakes in Greenland fit in the global methane budget compared to other, more well-studied areas of the Arctic, hence our work provides essential data for a more complete view of this rapidly changing region.

10.1371/journal.pone.0159642

others_280_9350

Rabbit antisera were produced against purified calf dermatosparatic procollagen and against the purified procollagens obtained from the culture medium of calf dermatosparatic cells. These antisera and their derived gamma-globulins were characterized by immunoprecipitation, double immunodiffusion and immunoelectrophoresis. Antiserum directed against dermatosparatic procollagen cross-reacted with the two different forms of procollagen obtained from the culture medium of dermatosparatic calf cells. Antiserum directed against onw of these procollagens, namely (pro alpha1)2 pro alpha2, cross reacted with dermatosparatic procollagen and also cross-reacted with the other procollagen,(pro alpha1)3. Antiserum directed against procollagen (pro alpha1)3 cross-reacted with dermatosparatic procollagen and with the procollagen (pro alpha1)2 pro alpha2. None of the antisera reacted with authentic calf skin collagen, or with the collagen extracted from the cell layer of the dermatosparatic calf cells in culture. Reduction andalkylation of the procollagens abolished the antigen-antibody reactions, while prior digestion of the antigens with bacterial collagenase did not eliminate the immunological reaction. Antigenic determinants in the cell culture procollagens were found at the COOH-terminal non-collagen peptide as well as at the NH2-terminal non-collagen peptid

others_280_9350

pubmed_1047_13772

We have cloned mouse and human cDNAs for a multifunctional DNA repair enzyme (APEX nuclease) having apurinic/apyrimidinic (AP) endonuclease, 3',5' exonuclease, DNA 3' repair diesterase and DNA 3'-phosphatase activities. To investigate the biological role of APEX nuclease, sense or antisense APEX RNA was stably expressed at a high level in cultured rat glioma cells by introducing plasmids (pABWN-HAPX1F for expression of sense RNA or pABWN-HAPX2R for expression of antisense RNA) constructed from the human APEX cDNA and an expression vector pABWN. Multiple copies of the construct were integrated into the glioma cells transfected with pABWN-HAPX1F or pABWN-HAPX2R. These transfectants showed markedly high expression of RNA hybridizable to human APEX cDNA, indicating the expression of the sense or antisense RNA. Activity blotting analyses of salt extracts of these transfectants showed that the sense RNA-expressed cells had higher AP endonuclease activity and that the antisense RNA-expressed cells had extremely lower AP endonuclease activity than the control cells. The APEX nuclease-depressed glioma cells became more sensitive to methyl methanesulfonate and hydrogen peroxide than the control cells or the APEX nuclease-overexpressed cells. The results indicate that APEX nuclease plays an important role in repair of DNA damage caused by these genotoxic agents. The present stable expression systems for the sense and antisense APEX RNAs should be useful for analyzing the biological functions such as an antimutagenic function of the enzyme.

10.1016/0921-8777(94)90028-0

pubmed_180_948

PURPOSE We sought to identify characteristics of genetic services that facilitate or hinder adoption. METHODS We conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology, pathology/laboratory medicine) within 13 Veterans Administration facilities. RESULTS Genetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as advantageous for their facilities or their patients; compatible with organizational norms of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had knowledgeable clinicians interested in developing services and organizational-level facilitators such as accessible genetic test-ordering processes. CONCLUSION Adoption and implementation of genetic services will require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of genetic information for the outcomes that matter to health-care organizations.

10.1038/gim.2013.101

others_164_7224

ween 1982 and 1992, 14% (109/662) of patients diagnosed with oesophageal cancer at Songklanagarind Hospital, Southern Thailand, were treated with radiotherapy only. The group included patients with advanced, non-resectable tumours and patients with resectable tumours who refused to undergo surgery. Radiotherapy was planned with curative or palliative intent and radiation administered either by conventional fractionation (no greater than 2.0 Gy/day) or accelerated fractionation (greater than 2.0 Gy/day) 10% of patients failed to respond to treatment and complications developed in 11%. The estimated overall 5-year survival rate was 10%. Multivariate Cox regression analysis incorporating patients' sex and age, tumour length, type. differentiation and staging, and treatment plan, revealed a significantly worse survival associated independently with palliative treatment (p < 0.001) and with accelerated fractionation (p = 0.001), irrespective of total dose. Accelerated fractionation was also independently associated with a higher rate of local recurrence than was conventional fractionation, irrespective of total dos

10.1093/dote/7.2.122

pubmed_608_5900

PURPOSE The purpose of the study was to evaluate the feasibility of using contrast-enhanced computed tomography (CECT)-based texture analysis (CTTA) metrics to differentiate between juxtatumoral perinephric fat (JPF) surrounding low-grade (ISUP 1-2) versus high-grade (ISUP 3-4) clear cell renal cell carcinoma (ccRCC). METHODS In this IRB-approved study, we retrospectively queried the surgical database between June 2009 and April 2016 and identified 83 patients with pathologically confirmed ccRCC (low grade: n = 54, mean age = 61.5 years, 18F/35M; high grade n = 30, mean age = 61.7 years, 8F/22M) who also had pre-operative multiphase CT acquisitions. CT images were transferred to a 3D workstation, and nephrographic phase JPF regions were manually segmented. Using an in-house developed Matlab program, a CTTA panel comprising of texture metrics extracted using six different methods, histogram, 2D- and 3D-Gray-level co-occurrence matrix (GLCM) and Gray-level difference matrix (GLDM), and 2D-Fast Fourier Transform (FFT) analyses, was applied to the segmented images to assess JPF textural heterogeneity in low- versus high-grade ccRCC. Univariate analysis and receiver-operator characteristics (ROC) analysis were used to assess interclass differences in texture metrics and their prediction accuracy, respectively. RESULTS All methods except GLCM consistently revealed increased heterogeneity in the JPF surrounding high- versus low-grade ccRCC. FFT showed increased complexity index (p < 0.01). Histogram analysis showed increased kurtosis and positive skewness in (p < 0.03), and GLDM analysis showed decreased measure of correlation coefficient (MCC) (p < 0.04). Several of the GLCM metrics showed statistically significant (p < 0.04) textural differences between the two groups, but with no consistent trend. ROC analysis showed that MCC in GLCM analysis had an area under the curve of 0.75. CONCLUSIONS Our study suggests that CTTA of ccRCC shows statistically significant textural differences in JPF surrounding high- versus low-grade ccRCC.

10.1007/s00261-018-1848-x

pubmed_910_14900

BACKGROUND The Affordable Care Act calls for increased integration and coordination of behavioral health services, as people with co-occurring disorders (CODs), meeting criteria for both substance use and psychiatric disorders, are overrepresented in treatment samples. Nationwide estimates of mental health (MH) service co-location in substance use disorder (SUD) treatment facilities are needed. We empirically derived a multiple-indicator categorization of services for CODs in SUD treatment facilities. METHODS We used latent class analysis to categorize 14,037 SUD treatment facilities in the United States and territories included in the 2012 National Survey of Substance Abuse Treatment Services. Latent class indicators included MH screening and diagnosis, MH support services, psychiatric medications, groups for CODs, and psychosocial approaches. Multinomial logistic regression compared facility-identified primary focus (i.e., SUD, MH, mix of SUD-MH, and general/other) and other facility characteristics across classes. RESULTS A four-class solution was chosen with the following classes: Comprehensive MH/COD Services (25%), MH without COD Services (25%), MH Screening Services (21%), and Limited MH Services (29%). The former two classes with co-located MH services were less likely to report a SUD-primary focus than the latter classes reporting only MH screening or Limited MH Services. Only the Comprehensive MH/COD Services class also had a high probability of providing special groups for CODs. CONCLUSIONS Approximately half of SUD treatment facilities were in classes with co-located mental health services, but only a quarter provided comprehensive COD services. Future studies should assess differences in patient experiences and treatment outcomes across facilities with and without COD services.

pubmed_910_14900

pubmed_760_25772

OBJECTIVE Tobacco smoking is a risk factor for gastroesophageal reflux, but whether other tobacco products increase the risk is unclear. The aim of this study was to investigate if snus increases the risk of gastroesophageal reflux symptoms (GERS). MATERIAL AND METHODS The study was based on the third Nord-Trøndelag health study (HUNT3), a population-based study of all adult residents in Nord-Trøndelag County, Norway, performed in 2006-2009. The association between self-reported severe heartburn/regurgitation and snus use was assessed by logistic regression. RESULTS Compared to never snus users, daily snus users had a reduced risk of GERS (OR 0.77, 95% confidence interval [CI] 0.64-0.93), while previous snus users and those using <2 boxes of snus/month had an increased risk (OR 1.20, 95% CI 1.00-1.46 and OR 1.41, 95% CI 1.02-1.96, respectively). There was no association between age when starting using snus and GERS. Snus users who started using snus to quit or cut down on cigarette smoking, who started using both snus and cigarettes or cigarettes alone had an increased risk of GERS. Snus users <30 years of age had an increased risk of GERS (OR 1.49, 95% CI 1.02-2.16), while those aged between 50-60 and 60-70 years had a reduced risk (OR 0.67, 95% CI 0.49-0.93 and OR 0.51, 95% CI 0.28-0.94, respectively). CONCLUSIONS Daily snus users had a reduced risk of GERS. However, previous snus users and subgroups of snus users had an increased risk of GERS indicating reverse causality, such that snus use could increase the risk of GERS.

10.1080/00365521.2016.1245775

pubmed_1128_12128

Reconstituted collagen fibres have potential applications in repair of soft and hard tissues. Preliminary studies conducted in our laboratory suggest that discontinuous reconstituted type I fibres have strengths similar to those of fibres teased from tendons. The purpose of this paper is to report a method for continuous collagen fibre production and the properties of fibres produced. Ultimate tensile mechanical properties and biocompatibility of continuous type I collagen fibres were studied and compared with the properties of fibres produced manually (discontinuous fibres). In general, continuously made cyanamide cross-linked fibres show slightly inferior mechanical properties and faster biodegradation rates compared with manually made fibres because of minor differences in the fibreformation protocol introduced by design constraints. However, continuous and discontinuous fibres crosslinked with glutaraldehyde had comparable properties. These results demonstrate that production of 50 microns diameter continuous collagen fibre is possible.

10.1016/0142-9612(90)90150-o

pubmed_692_3062

Class II transactivator (CIITA) is an effective transcriptional factor regulating various genes in the immune system. Since the detection of CIITA in 1993, there has been considerable progress toward understanding its role as an activator of MHC II genes in human and mouse; however, there is little knowledge of this gene in other animals such as chicken. Molecular characterization of the chicken CIITA gene transcript was performed to determine its sequence and expression in different tissues. The CIITA cDNA was first generated through reverse transcriptase-polymerase chain reaction (RT-PCR) from Cobb chicken spleen cell RNA, using oligonucleotide primers based on the predicted cDNA sequence. The effect of the immune system stimulation on the CIITA gene expression in kidney, liver, thymus, and spleen were assessed by semi-quantitative RT-PCR analysis. A partial cDNA sequence (1,688 bp) encoding part of the NACHT domain followed by seven of the transactivator and one of the NLS domains were obtained. Comparison of the deduced amino acid sequence with other CIITAs reveals high level of similarities in amino acid composition, secondary structure and phosphorylation sites. Furthermore, in comparison to the Red Jungle Fowl (RJF) sequence, we found 17 single nucleotide polymorphisms in Cobb broiler chicken, ten of which were reported for the first time. Gene expression analysis indicated that CIITA RNA amounts increased in all the examined tissues following stimulation with Brucella antigen. This investigation may indicate that CIITA molecule has an important role in the chicken immune responses as well as human and other animals.

10.1007/s00251-014-0810-5

pubmed_325_6566

Type VI secretion (T6S) is a cell-to-cell injection system that can be used as a microbial weapon. T6S kills vulnerable cells, and is present in close to 25% of sequenced Gram-negative bacteria. To examine the ecological role of T6S among bacteria, we competed self-immune T6S+ cells and T6S-sensitive cells in simulated range expansions. As killing takes place only at the interface between sensitive and T6S+ strains, while growth takes place everywhere, sufficiently large domains of sensitive cells can achieve net growth in the face of attack. Indeed T6S-sensitive cells can often outgrow their T6S+ competitors. We validated these findings through in vivo competition experiments between T6S+ Vibrio cholerae and T6S-sensitive Escherichia coli. We found that E. coli can survive and even dominate so long as they have an adequate opportunity to form microcolonies at the outset of the competition. Finally, in simulated competitions between two equivalent and mutually sensitive T6S+ strains, the more numerous strain has an advantage that increases with the T6S attack rate. We conclude that sufficiently large domains of T6S-sensitive individuals can survive attack and potentially outcompete self-immune T6S+ bacteria.

10.1371/journal.pcbi.1004520

pubmed_780_9887

The ability of ovine placental lactogen (oPL) to bind to the growth hormone receptor (GHR) raises the possibility that oPL may exert a growth hormone (GH)-like action on galactopoiesis. We have compared the effects of treating lactating ewes for 5 days with an equimolar dose (0.1 mg/kg/day, administered as two equal doses 12 hourly) of either bovine growth hormone (bGH) (n = 10), oPL (n = 10) or saline (n = 9) on hepatic and mammary GHR, insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) gene expression and hepatic GHR number. Hepatic GHR and IGFBP-3 mRNA were unaltered by bGH or oPL treatment. Hepatic IGF-I mRNAs increased following bGH (P < 0.05) but not oPL treatment. GHR gene expression was greater in liver compared to mammary gland extracts. There was no effect of either bGH or oPL treatment on mammary GHR, IGF-I or IGFBP-3 mRNA or hepatic GHR number. These studies confirm the galactopoietic effects of bGH in lactating ruminants and suggest that the mechanism of this action is not via increased hepatic GHR number or gene expression. In addition, the increase in hepatic but not mammary IGF-I mRNA with bGH treatment suggests an endocrine action of IGF-I on milk synthesis. These studies also demonstrate that an equimolar dose of oPL is not galactopoietic or somatogenic in the lactating ewe.

10.1016/s1096-6374(98)80296-7

pubmed_433_16698

Designed ecosystems are built as part of ongoing urban expansion, providing a suite of valued ecosystem services. However, these new ecosystems could also promote disservices by facilitating the colonization and spread of invasive species. We conduct the first assessment of the quantity and invasion of an overlooked designed ecosystem: stormwater ponds. These ponds are commonly recommended for managing urban hydrology, but little is known about their ecology or extent of proliferation. Using a broad-scale survey of pond coverage in Florida, USA, we found that over 76,000 stormwater ponds have been built just in this state, forming 2.7% of total urban land cover. This extensive pondscape of manufactured habitats could facilitate species spread throughout urban areas and into nearby natural waterbodies. We also conducted a survey of the severity of plant invasion in 30 ponds in Gainesville, FL, US across two pond types (dry vs. wet), and a gradient of management intensities (low, medium, high) and pond ages. We unexpectedly found a high number of invasive plant species (28 in just 30 ponds). Ninety-six percent of surveyed ponds contained from one to ten of these species, with ponds exhibiting high turnover in invader composition (i.e., high beta diversity). The bank sections of dry unmanaged ponds exhibited the highest mean invasive species richness (5.8 ± 1.3) and the inundated centers of wet medium managed ponds exhibited the highest mean invasive species cover (34 ± 12%). Invasive plant richness and cover also tended to be greater in dry ponds with higher soil nutrient levels, and in older wet ponds. Therefore, we found that highly maintained and younger wet ponds were the least invaded. Nevertheless, common management practices that limit plant invasions may also limit native species establishment and invasion may increase in the decades following pond construction.

10.1016/j.scitotenv.2019.135133

pubmed_746_5898

Two cellulase cDNAs (GHF10-Pc1 and GHF10-Pc3) belonging to glycoside hydrolase family 10 (GHF10) were successfully isolated and characterized from stomach tissue of golden apple snail (Pomacea canaliculata), a kind of herbivorous mollusca. Sequencing analysis revealed full-length cDNAs of 1300 and 1277 bp in length, respectively. The open reading frame (ORF) of cellulase cDNA was 1188 and 1191 bp, encoding 395 and 396 amino acid, respectively. Sequence alignment revealed that GHF10-Pc1 and GHF10-Pc3 shared high identity with glycosyl hydrolase family 10 (GHF10) and had an overall similarity of 98 and 82% to those of Ampullaria crossean cellulase EGX. A neighbour-joining tree showed a clear differentiation between each species and also indicated that GHF10-Pc1 and GHF10-Pc3 from P. canaliculata and A. crossean EGX are closely related phylogenetically. The genomic organization of cellulase GHF10-Pc1 and GHF10-Pc3 genes was also investigated. The GHF10-Pc1 and GHF10-Pc3 genes spanned over 4937 and 4512 bp, respectively. Both genes contained 9 exons interrupted by eight introns. The result verified the endogenous origin of the GHF10-Pc1 and GHF10-Pc3 genes. Analysis of RNA by RT-PCR from several ages of P. canaliculata revealed that neither gene was expressed in eggs. GHF10-Pc1 was also expressed in 1- and 10-day-old juvenile snails whereas GHF10-Pc3 was expressed only in 1-day-old juvenile snails. The result showed that two GHF10-Pc transcripts were developmentally expressed.

10.1080/10425170701517911

pubmed_1025_22821

A newly recognized primary cause of obesity epidemic is the developmental programming effects of (1) intrauterine growth-restricted (IUGR) newborns exposed in utero to undernutrition, and (2) normal or excessive weight newborns exposed to maternal obesity and high-fat (HF) diets. The mechanisms contributing to offspring obesity have been extensively studied in animal models with adipose tissue identified as one of the principal targets of programming. IUGR and HF offspring exhibit programmed adipocytes, such that an intrinsic enhanced lipogenesis and adipocyte proliferation contribute to the development of obesity. This is attributed to early induction of adipogenic transcription factor peroxisome proliferator-activated receptor (PPAR)γ, whose activity is enhanced under limited or excess nutrient availability. Nonetheless, this occurs via different mechanisms involving PPARγ coregulators: In IUGR, it is upregulation of coactivators, whereas in HF newborns, it is downregulation of corepressors. Thus preventive therapeutic interventions will require target-specific modalities that depend on the primary etiology.

10.1055/s-0031-1275517

pubmed_965_14064

An efficient and modulable total synthesis of discodermolide (DDM), a unique marine anticancer polyketide is described including related alternative synthetic approaches. Particularly notable is the repeated application of a crotyltitanation reaction to yield homoallylic (Z)-O-ene-carbamate alcohols with excellent selectivity. Advantage was taken of this reaction not only for the stereocontrolled building of the syn-anti methyl-hydroxy-methyl triads of DDM, but also for the direct construction of the terminal (Z)-diene. Of particular interest is also the installation of the C13=C14 (Z)-double bond through a highly selective dyotropic rearrangement. The preparation of the middle C8-C14 fragment in two sequential stages and its coupling to the C1-C7 moiety was a real challenge and required careful optimization. Several synthetic routes were explored to allow high and reliable yields. Due to the flexibility and robust character of this approach, it might enable a systematic structural variation of DDM and, therefore, the elaboration and exploration of novel discodermolide structural analogues.

10.1002/chem.200801478

pubmed_732_20651

Mammalian hearts express two myosin heavy chain (MHC) isoforms, which drive contractions with different kinetics and power-generating ability. The expression of the isoform that is associated with more rapid contraction kinetics and greater power output, MHC-α, is downregulated, with a concurrent increase in the relative amount of the slower isoform, MHC-β, during the progression to experimentally induced or disease-related heart failure. This change in protein expression has been well studied in right and left ventricles in heart failure models and in humans with failure. Relatively little quantitative data exists regarding MHC isoform expression shifts in human failing atria. We previously reported significant increases in the relative amount of MHC-β in the human failing left atrium. The results of that study suggested that there might be a sex-related difference in the level of MHC-β in the left atrium, but the number of female subjects was insufficient for statistical analysis. The objective of this study was to test whether there is, in fact, a sex-related difference in the level of MHC-β in the right and left atria of humans with cardiomyopathy. The results indicate that significant differences exist in atrial MHC isoform expression between men and women who are in failure. The results also revealed an unexpected twofold greater amount of MHC-β in the nonfailing left atrium of women, compared with men. The observed sex-related differences in MHC isoform expression could impact ventricular diastolic filling during normal daily activities, as well as during physiologically stressful events.

10.1152/ajpheart.00810.2013

pubmed_305_11848

To develop a risk stratification model based on complete blood count (CBC) components in patients with acute coronary syndrome (ACS) using a classification and regression tree (CART) method. CBC variables and the Global Registry of Acute Coronary Events (GRACE) scores were determined in 2,693 patients with ACS. The CART analysis was performed to classify patients into different homogeneous risk groups and to determine predictors for major adverse cardiovascular events (MACEs) at 1-year follow-up. The CART algorithm identified the white blood cell count, hemoglobin, and mean platelet volume levels as the best combination to predict MACE risk. Patients were stratified into three categories with MACE rates ranging from 3.0% to 29.8%. Kaplan-Meier analysis demonstrated MACE risk increased with the ascending order of the CART risk categories. Multivariate Cox regression analysis showed that the CART risk categories independently predicted MACE risk. The predictive accuracy of the CART risk categories was tested by measuring discrimination and graphically assessing the calibration. Furthermore, the combined use of the CART risk categories and GRACE scores yielded a more accurate predictive value for MACEs. Patients with ACS can be readily stratified into distinct prognostic categories using the CART risk stratification tool on the basis of CBC components.

10.1038/s41598-018-21139-w

pubmed_26_22819

A biosurfactant-producing strain was isolated from the production water of an oil-field and was identified as Bacillus subtilis HOB2 by 16S rRNA gene sequencing. The production of biosurfactant by Bacillus subtilis HOB2 has been investigated using different carbon and nitrogen sources, under thermophilic and mesophilic conditions. The strain was able to grow and to produce surfactant, reducing the surface tension of medium to 27 mN/m on sucrose, and 28 mN/m on glucose after 24 h of cultivation. The strain was able to produce the maximum amount of biosurfactant when ammonium ions were used as nitrogen source. The surface-active compound was stable during exposure to elevate temperature (100degreesC), high salinity (25% NaCl) and a wide range of pH values (5.0-11.0). The biosurfactant was capable of forming a promising emulsification index (E(24)= 68%) with kerosene. The kinetic studies revealed that biosurfactant production is a cell growth-associated process. Preliminary chemical characterization revealed that the surfactant has a lipopeptide composition similar to surfactin as confirmed by TLC and IR analysis. Properties and characteristics of the biosurfactant produced by Bacillus subtilis HOB2 suggesting potential commercial applications, such as enhanced oil recovery, bioremediation of soil and marine environments, and food industries.

10.2174/092986609787049358

pubmed_900_8512

Colchicine poisoning is an uncommon, but potentially life-threatening, toxicologic emergency. The clinical features associated with overdose and the options for treatment are discussed. Colchicine poisoning typically shows 3 phases: initially, gastrointestinal symptoms predominate; in the second phase, multiorgan failure may occur, possibly leading to death. If the patient survives, the third phase of recovery follows, during which the patient often presents with hair loss. Early fatality is due to cardiovascular collapse and respiratory failure; however, pancytopenia and overwhelming septicemia can occur later. All patients suspected of having colchicine intoxication because of its unpredictable outcome should be managed according to the principles of intensive care, irrespective of the actual degree of poisoning. In those patients who survive the initial phase of poisoning, filgrastim (granulocyte colony-stimulating factor) offers an effective method of treating pancytopenia and preventing overwhelming septicemia. Daily monitoring of the patients' hematological status is strongly recommended. We are reporting a case of previously healthy girl who developed a multisystem organ failure after colchicine intoxication. The patient recovered completely and had no residual outcome.

10.1097/01.pec.0000270163.84076.9f

pubmed_1032_21784

INTRODUCTION Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is linked to endothelial dysfunction; a key factor in pre-eclamptic pathogenesis. This study aimed to compare sTWEAK levels during pregnancy to assess for its prognostic ability. MATERIALS AND METHODS Sixty three high risk pregnant women were followed up from 12 weeks of gestation till term. Serum levels of sTWEAK and platelet derived growth factor (PlGF), blood pressure, serum glucose, uric acid, urea/creatinine and liver function tests were measured. Subjects were stratified according to the ACOG criteria as women who developed PE, or PIH or remained normotensive at term. A negative control group of normotensive healthy pregnant women (n = 17) was also recruited for comparison. RESULTS Baseline sTWEAK levels were lower (4.03 ± 0.37 ng/dl) in HR cohort that developed PE and further reduced at term (1.93 ± 0.23 ng/dl) as compared to HR subjects who remained normotensive and negative control group (30.53 ± 0.79 ng/dl; p < 0.01). Likewise PlGF levels were significantly lower (74.22 ± 10.11 pg/ml) in HR cohort that developed PE (p = 0.013). At term 39.68% (n = 22) HR subjects with low sTWEAK developed PIH and 34.92% (n = 24) developed PE. In terms of high risk characteristics observed in the HR group; 73% of the subjects were multiparous, whereas 26.98% reported to have developed PE in previous pregnancies. CONCLUSION sTWEAK levels at early pregnancy weeks were found to be low in high risk females who developed PE at follow up versus normotensive pregnant women. Baseline TWEAK might serve as an independent variable for prediction of pre-eclampsia; however longitudinal studies with larger sample size are required to ascertain the causal relation.

10.1016/j.ejogrb.2019.01.020

pubmed_263_2587

Temporal lobe epilepsy (TLE) is the most common form of acquired epilepsy in adult. Since dentate gyrus granule cells (GCs) play a critical role in hippocampal seizure generation, it is, therefore, important to understand changes in intrinsic properties of GCs in TLE. In this study, the electrophysiological properties of GCs obtained from epileptic rates were compared with the control group using whole cell patch-clamp recording. Results indicated a significant increase in the number of action potentials (APs) in depolarizing currents of 150 pA, 200 pA, and 250 pA. In addition, there was a significant decrease in AP half-width of GCs. The amplitude of fast afterhyperpolarization (fAHP) in epileptic group significantly decreased compared to control group. Blockade of large conductance calcium activated potassium channel (BK), channels with paxilline and iberiotoxin reversed pilocarpine-induced changes in electrophysiological properties of GCs in epileptic group. These results suggest that the BK channel blockers by reversing the firing properties of GCs might have beneficial preventative effects on pilocarpine-induced electrophysiological changes.

pubmed_263_2587

others_52_11341

Peripheral blood and bone marrow analysis of a 79-year-old female led to a diagnosis of acute myeloblastic leukemia with differentiation (AML-M2). Chromosome analysis of the unstimulated bone marrow cells revealed 48, XX,+21,+21, and tetrasomy 21 was the sole cytogenetic abnormality in this constitutionally normal female patient. © Elsevier Science Inc. All rights reser

10.1016/S0165-4608(01)00408-3

pubmed_494_4715

In hypophosphatemic rickets, there are both inherited and acquired forms, where X-linked dominant hypophosphatemic rickets (XLH) is the most prevalent genetic form and caused by mutations in the phosphate-regulating endopeptidase (PHEX) gene. XLH is associated with growth retardation and bone deformities. The renal tubular cells have an important role in calcium and phosphate metabolism, where the 1alpha-hydroxylase enzyme metabolizes the conversion of 25 (OH)-vitamin D to potent 1,25 (OH)2-vitamin D, whereas the sodium-phosphate transporter controls tubular phosphate reabsorption. The pathophysiological defect in XLH is speculated to cause an increase in a circulating phosphate regulating hormone termed phosphatonin (fibroblast growth factor 23 is the primary phosphatonin candidate), which leads to inhibition of 1alpha-hydroxylase, and simultaneously to inhibition of the sodium-phosphate transporter domain NPT2c leading to parathyroid hormone-independent phosphaturia. Hence, current treatment of XLH is 1,25 (OH)2-vitamin D or the vitamin D analog alfacalcidol and elementary phosphorus. Unfortunately, patients with XLH may develop nephrocalcinosis, secondary or tertiary hyperparathyroidism, and in some situations also hypertension and cardiovascular abnormalities. We describe a patient with XLH caused by a novel missense mutation in the PHEX gene, who on treatment with alfacalcidol and oral phosphate had normal growth and minimal bone deformities, but who subsequently developed moderate nephrocalcinosis, significant hyperparathyroidism, hypercalcemia, renal failure, and hypertension. We also report the use of the calcimimetic drug cinacalcet in the successful treatment of hypercalcemia and hyperparathyroidism.

10.1530/EJE-08-0383

pubmed_485_15639

Acute hypoxic hypoxia is reported to suppress both diet- and cold-induced components of metabolism. In the present experiment the effects of hypoxic hypoxia on the oxygen consumption and on colonic and brown adipose tissue temperature were studied in rats with lesion of the lateral hypothalamus. The electroencephalographic activity, slow potential changes and cortical extracellular potassium concentration were also recorded. The results showed that acute hypoxic hypoxia blocked the thermogenesis induced by lateral hypothalamic lesion and the changes in temperatures were always preceded by modification of the cerebral cortex activity.

pubmed_485_15639

pubmed_1055_2629

BACKGROUND AND OBJECTIVES To study the associations between nutrient intake, dairy intake and socioeconomic variables. METHODS AND STUDY DESIGN Food consumption data using 24 h recall were collected in 3600 children, aged 0.5 to 12 years old in addition to frequency of dairy use and anthropometric and sociodemographic variables. RESULTS Overall height for age Z-score (HAZ) and body mass index for age Z-score (BAZ) values (mean±SE) were -1.40±0.03 and -0.48±0.03 respectively, associated with a high prevalence of stunting and thinness in the population. The overall percentage of children not using any dairy products was 71%, and this percentage increased steadily with age. The overall energy intake from dairy was 99±3 kcal/capita/day and the overall energy intake from dairy in dairy users was 291±7 kcal/day. Dairy use did not differ between boys and girls, but was higher in urban areas, higher if the education of the mother was higher and higher if the mother had a permanent job and if the wealth status of the family was in the upper levels. Nutrient intake after the age of 3 years was inadequate for energy and all nutrients except for protein. The achievement of Recommended Dietary Allowances (RDA) for all nutrients was higher in dairy users compared to non-dairy users, also after correcting for the confounding effect of the higher energy intake (from dairy) and socio-demographic variables. The contribution increased with increasing frequency of dairy use. CONCLUSION Adequate dairy intake can substantially add to the achievement of RDA in Indonesian children.

10.6133/apjcn.2016.25.2.09

pubmed_968_15221

Policies to prevent respiratory virus transmission in health care settings have traditionally divided organisms into Droplet versus Airborne categories. Droplet organisms (for example, influenza) are said to be transmitted via large respiratory secretions that rapidly fall to the ground within 1 to 2 meters and are adequately blocked by surgical masks. Airborne pathogens (for example, measles), by contrast, are transmitted by aerosols that are small enough and light enough to carry beyond 2 meters and to penetrate the gaps between masks and faces; health care workers are advised to wear N95 respirators and to place these patients in negative-pressure rooms. Respirators and negative-pressure rooms are also recommended when caring for patients with influenza or SARS-CoV-2 who are undergoing "aerosol-generating procedures," such as intubation. An increasing body of evidence, however, questions this framework. People routinely emit respiratory particles in a range of sizes, but most are aerosols, and most procedures do not generate meaningfully more aerosols than ordinary breathing, and far fewer than coughing, exercise, or labored breathing. Most transmission nonetheless occurs at close range because virus-laden aerosols are most concentrated at the source; they then diffuse and dilute with distance, making long-distance transmission rare in well-ventilated spaces. The primary risk factors for nosocomial transmission are community incidence rates, viral load, symptoms, proximity, duration of exposure, and poor ventilation. Failure to appreciate these factors may lead to underappreciation of some risks (for example, overestimation of the protection provided by medical masks, insufficient attention to ventilation) or misallocation of limited resources (for example, reserving N95 respirators and negative-pressure rooms only for aerosol-generating procedures or requiring negative-pressure rooms for all patients with SARS-CoV-2 infection regardless of stage of illness). Enhanced understanding of the factors governing respiratory pathogen transmission may inform the development of more effective policies to prevent nosocomial transmission of respiratory pathogens.

10.7326/M21-2780

pubmed_579_12105

In the present study, the in vitro cytotoxicity of daidzein was evaluated in human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. BEL-7402 cells were sensitive to daidzein treatment, with an IC50 value of 59.7±8.1 µM. Daidzein showed no cytotoxic activity toward A549, HeLa, HepG-2 and MG-63 cells. Daidzein increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Morphological and comet assays showed that daidzein effectively induced apoptosis in BEL-7402 cells. Additionally, daidzein caused cell cycle arrest at the G2/M phase in the BEL-7402 cell line. Daidzein downregulated the expression of Bcl-2, Bcl-x and Baid proteins and upregulated the levels of Bim protein in the BEL-7402 cells. The results demonstrated that daidzein induced BEL-7402 cell apoptosis through an ROS-mediated mitochondrial dysfunction pathway.

10.3892/or.2015.4133

pubmed_447_11703

Intravascular haemolysis has been found to result from prolonged endurance competition, rigorous military training and participation in impact sports. Haematological research involving the recreational runner is sparse. Recreational runners frequently vary their training to avoid monotony and improve endurance capacity. This study investigated the haematological effects of a typical day of increased distance training in 15 male recreational runners (62.4(3.1) ml kg-1 min-1 treadmill VO2max; 44.6(8.4) km per week training (means(s.d.)). Venous blood samples were collected before, immediately after, 1 day, 4 days, and 10 days after a 13-km training run (about twice the subjects' typical running distance) and analysed for changes in bilirubin, serum potassium, haematocrit, haemoglobin, red blood cell count, haptoglobin, poikilocytosis and reticulocytosis. Urine samples were collected at the same times as the blood samples and analysed for urobilinogen. Significant (P less than 0.05) 1-day and 4-day decreases in mean haemoglobin, red blood cell count, and haptoglobin values, compared to before training venous blood values and significant (P less than 0.05) post-training increases in bilirubin, serum potassium, urobilinogen and poikilocytosis provided evidence for increased intravascular haemolysis. After 10 days the values for haematocrit, bilirubin, serum potassium, red blood cell count, urobilinogen and poikilocytosis were not significantly (P less than 0.05) different from pre-training values while haemoglobin remained significantly (P less than 0.05) lower, exhibiting a constant but not significant increase over the period from 1 to 10 days. The results indicate that mild intravascular 'footstrike' haemolysis can occur in the recreational runner when typical training distance is increased. This condition appears to be transient and benign.

10.1136/bjsm.25.4.183

pubmed_1015_10015

A longitudinal study was performed to investigate the behavioral changes associated with occupational exposure to organic solvents. An initial simple reaction time (SRT) test was performed on a group of steel workers who were exposed to vapor concentrations of solvents clearly exceeding threshold limit values (TLVs). A second SRT measurement was made six months following the completion of major improvements in the hygiene quality of the work environment which resulted in a reduction of exposure levels to 20% of the TLVs valid at the time. Approximately fifteen months after this measurement, a final SRT test was performed. The workers' performance on the SRT test improved over the three measurements. At the first measurement occasion SRT was found to be related to the degree of exposure, while no such relation could be observed on the following measurement occasions. The results indicate that the workers' central nervous functioning had been negatively affected by solvent exposure and that this effect was at least partially reversible in nature; they thus confirm the importance of changes which enhance the hygienic quality of the work environment.

10.1007/BF00405609

pubmed_94_20843

Many countries have been experienced an increase in protein consumption due to the population growth and adoption of protein-rich dietaries. Unfortunately, conventional-based protein agroindustry is associated with environmental impacts that might aggravate as the humankind increase. Thus, it is important to screen for novel protein sources that are environmentally friendly. Microalgae farming is a promising alternative to couple the anthropic emissions with the production of food and feed. Some microalgae show protein contents two times higher than conventional protein sources. The use of whole microalgae biomass as a protein source in food and feed is simple and well-established. Conversely, the production of microalgae protein supplements and isolates requires the development of feasible and robust processes able to fractionate the microalgae biomass in different value-added products. Since most of the proteins are inside the microalgae cells, several techniques of disruption have been proposed to increase the efficiency to extract them. After the disruption of the microalgae cells, the proteins can be extracted, concentrated, isolated or purified allowing the development of different products. This critical review addresses the current state of the production of microalgae proteins for multifarious applications, and possibilities to concatenate the production of proteins and advanced biofuels.

10.1080/10408398.2020.1768046

pubmed_822_17988

Density functional calculations were performed at the B3LYP level using combined basis sets for the NO and bromine interactions with the Pt(111) surface mimicked by the two-layer Pt10 cluster model. It explains well an attractive bonding interaction not only for bromine and Pt(111) but also for all three adsorption modes of NO on the Pt(111) surface. In accordance with the experimental observations, the calculations predict that the first peak in the IR spectra appears at around 1515 cm(-)(1) at the initial stage of low NO coverage, while it would shift to 1707 cm(-)(1) at high NO coverage. The bonding of NO on the 3-fold hollow fcc and hcp sites of Pt(111) proceeds via predominant back-donation interactions, while for the on-top adsorption, both the donation and back-donation interactions become equally important. Energetic criteria show also that the STM tip (made from Pt and Ir alloys) immersed into a bromine solution may contain only dissociated bromine atoms that bind strongly with the surface Pt atoms. As a result, the νBrBr stretching vibration mode for the bromine molecule may not be seen in the IR spectra because of its dissociation into adsorbed atoms. This leads to an appearance of a blue shifted band centered at ca. 202 cm(-)(1).

10.1021/ct050308m

pubmed_1025_6814

Alzheimer's disease (AD) is the most common type of dementia in aging adults, and a substantial burden to patients, caregivers, and the healthcare system. It is an increasingly significant public health issue; with the number of people living with AD projected to increase dramatically over the next few decades, making the search for treatments and tools to measure disease progression increasingly urgent. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. The subject headings and keywords used were Alzheimer's disease, dementia, primary neuronal degeneration and senile plagues. Only the articles written in English were included. The diagnosis is still primarily made based on history and physical and neurologic examinations. Approved treatments are few and of limited efficacy, serving mostly to slow or delay progression and not to cure the disease, despite significant research by pharmaceutical industries. Cholinesterase inhibitors offer some help in treating cognitive and global functioning, as well as behavioral abnormalities in patients with mild-, moderate-, or severe-stage disease. The N-methyl-d-aspartate (NMDA) antagonist, memantine, is similarly effective alone or in combination with cholinesterase inhibitors in moderate to severe stages of the disease. Recent insights into the pathophysiology of AD have led to promising investigational therapies, including the development of γ- and β-secretase inhibitors as well as active and passive immunization against the amyloid β-protein.

10.4103/1596-3519.82057

others_279_249

Every spring, workers of the Argentine Ant Linepithema humile kill a large proportion of queens within their nests, Although this behaviour inflicts a high energetic cost oil the colonies, its biological significance has remained elusive so far. An earlier study showed that the probability of a queen being executed is not related to her weight, fecundity, or age. Here we test the hypothesis that workers collectively eliminate queens to which they are less related, thereby increasing their inclusive fitness. We found no evidence for this hypothesis. Workers of a nest were on average not significantly less related to executed queens than to surviving ones. Moreover, a population genetic analysis revealed that workers were not genetically differentiated between nests. This means that workers of a given nest are equally related to any queen in the population and that there can be no increase in average worker-queen relatedness by selective elimination of queens. Finally, our genetic analyses also showed that, in contrast to workers, queens were significantly genetically differentiated between nests and that there was significant isolation by distance for queens

10.1046/j.1420-9101.2001.00345.x

pubmed_285_3434

INTRODUCTION Adolescent depression is associated with serious consequences. School staff is in a unique position to screen and refer adolescents with depression in a timely manner, and can collaborate with healthcare teams to assist in the proper management of the disease. The objective of this paper is to describe the results of a workshop that aims to improve the knowledge of adolescent depression among school staff. MATERIALS AND METHODS This was a single-arm trial with a pre-post design. Six workshops were conducted in four cities in Chile. Each workshop lasted 4 h. Participatory methodology was used. A 26-item knowledge questionnaire about adolescent depression, with the alternatives "I agree," "I disagree," and "I don't know," was administered to the participants, before and after the workshop. RESULTS A total of 152 people participated in the trial. Of these, 74.3% were female, and 44.7% were school psychologists, 25.0%, teachers, 17.8%, school counselors, and 5.3%, social workers. On average, there were 69.6% (SD 21.3) correct responses on the initial test, and 91.8% (SD 8.0) on the final test. All items had an increase of correct answers and a decrease of "don't know" answers. There were notable increases of correct responses on statements dealing with myths: "Antidepressants for the treatment of depression in adolescents must be avoided because they produce dependence" (59-96%), and "Depression in adolescence is better defined as a weakness of character than as a disease" (75-95%). School psychologists scored higher than the other participants on the questionnaire both before and after the workshop. CONCLUSION The workshop: "Adolescent depression: What can schools do?" can improve school staff knowledge of this topic, especially aiding to dispel myths regarding the disease and its treatment. This can help bring about timely case detection and improved collaboration with health team for proper handling of adolescent depression.

10.3389/fpsyt.2015.00067

pubmed_1039_7735

Plasma VIII:von Willebrand factor antigen (VIII:vWF) levels were elevated approximately two- to eightfold in seven patients (three adults and four children) during acute episodes of thrombocytopenia, renal failure, and hemolytic anemia (the hemolytic-uremic syndrome, HUS). In all seven patients, there was an alteration in plasma VIII:vWF patterns during these acute HUS episodes, so that the largest VIII:vWF forms were relatively decreased. Plasma VIII:vWF multimer patterns returned to normal, or nearly to normal, as platelet counts returned to preexisting levels, even in the patients whose recovery of renal function was incomplete and whose plasma VIII:vWF antigen level remained above normal. The sister of one of the HUS patients had a similar clinical prodrome (gastroenteritis) that was not followed by thrombocytopenia or renal failure and was not accompanied by an elevated level or abnormal forms of plasma VIII:vWF. These results suggest that an alteration in VIII:vWF metabolism, distribution, or interaction with platelets is associated with acute HUS episodes. In contrast to patients with chronic relapsing thrombotic thrombocytopenic purpura, none of the HUS patients (either during or after the acute HUS episodes) had a defect in the conversion of unusually large VIII:vWF multimers derived from endothelial cells to the VIII:vWF forms found in normal plasma.

pubmed_1039_7735

pubmed_723_20662

CO2 geological sequestration in coal seams has gradually become one of the effective means to deal with the global greenhouse effect. However, the injection of CO2 into the coal seam can have an important impact on the physical and chemical properties of coal, which in turn affects the CO2 sequestration performance in coal seams and causes a large number of environmental problems. In order to better evaluate the strength alteration of coal in CO2 geological sequestration, a hybrid artificial intelligence model integrating back propagation neural network (BPNN), genetic algorithm (GA) and adaptive boosting algorithm (AdaBoost) is proposed. A total of 112 data samples for unconfined compressive strength (UCS) are retrieved from the reported studies to train and verify the proposed model. The input variables for the predictive model include coal rank, CO2 interaction time, CO2 interaction temperature and CO2 saturation pressure, and the corresponding output variable is the measured UCS. The predictive model performance is evaluated by correlation coefficient (R), root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE). The predictive results denote that the GA-BPNN-AdaBoost predictive model is an efficient and accurate method to predict coal strength alteration induced by CO2 adsorption. The simultaneous optimization of BPNN by GA and AdaBoost algorithm can greatly improve the prediction accuracy and generalization ability of the model. At the same time, the mean impact value (MIV) is used to investigate the relative importance of each input variable. The relative importance scores of coal rank, CO2 interaction time, CO2 interaction temperature and CO2 saturation pressure are 0.5475, 0.2822, 0.0373, 0.1330, respectively. The research results in this paper can provide important guiding significance for CO2 geological sequestration in coal seams.

10.1016/j.scitotenv.2019.135029

pubmed_506_869

Predation is one of the main causes of adult mortality and breeding failure for ground-nesting birds. Micro-habitat structure around nests plays a critical role in minimizing predation risk. Plovers nest in sites with little vegetation cover to maximize the incubating adult visibility, but many studies suggest a trade-off between nest-crypsis and predator detection strategies. However, this trade-off has not been explored in detail because methods used so far do not allow estimating the visibility with regards to critical factors such as slope or plant permeability to vision. Here, we tested the hypothesis that Kentish plovers select exposed sites according to a predator detection strategy, and the hypothesis that more concealed nests survive longer according to a crypsis strategy. To this end, we obtained an accurate estimation of the incubating adult's field of vision through a custom built inverted periscope. Our results showed that plovers selected nest sites with higher visibility than control points randomly selected with regards to humans and dogs, although nests located in sites with higher vegetation cover survived longer. In addition, the flushing distance (i.e., the distance at which incubating adults leave the nest when they detect a potential predator) decreased with vegetation cover. Consequently, the advantages of concealing the nest were limited by the ability to detect predators, thus indirectly supporting the existence of the trade-off between crypsis and predator detection. Finally, human disturbance also constrained nest choice, forcing plovers to move to inland sites that were less suitable because of higher vegetation cover, and modulated flushing behavior, since plovers that were habituated to humans left their nests closer to potential predators. This constraint on the width of suitable breeding habitat is particularly relevant for the conservation of Kentish Plover in sand beaches, especially under the current context of coastal regression and increase of recreational activities.

10.1371/journal.pone.0107121

pubmed_289_14754

AIM Patients prefer minimally invasive procedures with fast recovery, minimal pain and good cosmesis. Single-port cholecystectomy may decrease the need for narcotic pain medication and thus shorten recovery. Outcome-based evidence for this procedure is still being assembled. METHODS Single-port cholecystectomy patients were matched based on age and gender with control patients undergoing four-port cholecystectomy during the same time. The primary endpoint was in hospital use of narcotic pain medication, measured by morphine equivalents. Secondary endpoints were operative time and length of stay. Statistical analysis was done by Student's t-test. RESULTS Fifty patients (36 women, 14 men) underwent single port cholecystectomy between 11/2009-7/2012 and 50 patients underwent traditional cholecystectomy during the same time period. All patients were matched within 10 years of age. Morbidity was 4% for the single port group, 0% for the traditional cholecystectomy. There were no conversions to open cholecystectomy. The single-port group required a median of 29.0 mg (range, 8.7-180 mg) morphine equivalents of pain medication and the control group required a median of 33.2 mg (range, 0-185.7 mg) morphine equivalents (P=0.04). Single port cholecystectomy operative times were longer (median, 85 vs. 77 minutes, P=0.03). CONCLUSION In this small study, there is a statistically significant difference in narcotic use during the initial hospital stay was measured between the two groups. After the initial ten cases, the operative time for single-port cholecystectomy approximated the standard four-port cholecystectomy. Prospective randomized controlled trials are necessary to investigate differences in outcomes between the two approaches.

pubmed_289_14754

pubmed_354_16023

Heparin anticoagulant therapy for thromboembolic disorders during pregnancy is problematic due to unexpected adverse bleeding. To avoid bleeding, we have used a less-intensive anticoagulation protocol of unfractionated heparin (UFH). The protocol had a therapeutic activated partial thromboplastin time (APTT) ratio of 1.5-2.0 with the control value, a UFH dose of ≤ 30,000 U/day, and an antithrombin (AT) activity target of ≥ 70%. In the present study, we evaluated this protocol using an anti-Xa assay. We collected UFH-treated plasma samples from ten consecutive pregnant Japanese patients with current or previous thromboembolic disorders. Seven patients remained in the therapeutic APTT ratio range (heparin-sensitive [HS] group). The other three patients had difficulty remaining within the therapeutic range (heparin-resistant [HR] group). In the HR group, two had AT deficiency and one had congenital absence of the inferior vena cava. Of the HS and HR samples, 73% and 31%, respectively, were within the therapeutic anti-Xa activity range 0.3-0.7 U/mL, indicating difficulty for the HR group to remain within the therapeutic range. Neither major bleeding nor symptomatic thromboembolic episodes occurred in either group. These findings suggest that the less-intensive anticoagulation protocol is permissive and may be beneficial in the HS group.

10.1007/s12185-019-02712-z

pubmed_950_10184

With the increasing incidence of neurodegenerative disorders, there is an urgent need to understand the protein folding process. Examining the folding process of multidomain proteins remains a prime challenge, as their complex conformational dynamics make them highly susceptible to misfolding and/or aggregation. The presence of multiple domains in a protein can lead to interaction between the partially folded domains, thereby driving misfolding and/or aggregation. Calnuc is one such multidomain protein for which Ca2+ binding plays a pivotal role in governing its structural dynamics and stability and, presumably, in directing its interactions with other proteins. We demonstrate differential structural dynamics between the Ca2+-free and Ca2+-bound forms of calnuc. In the absence of Ca2+, full-length calnuc displays equilibrium structural transitions with four intermediate states, reporting a sum of the behavioral properties of its individual domains. Fragment-based studies illustrate the sequential events of structure adoption proceeding in the following order: EF domain followed by the NT and LZ domains in the apo state. On the other hand, Ca2+ binding increases domain cooperativity and enables the protein to fold as a single unit. Single-tryptophan mutant proteins, designed in a domain-dependent manner, confirm an increase in the number of interdomain interactions in the Ca2+-bound form as compared to the Ca2+-free state of the protein, thereby providing insight into its folding process. The attenuated domain crosstalk in apo-calnuc is likely to influence and regulate its physiologically important intermolecular interactions.

10.1021/acs.biochem.0c00207

pubmed_87_3699

Spatial abilities have been related in previous studies to three-dimensional (3D) anatomy knowledge and the performance in technical skills. The objective of this study was to relate spatial abilities to residency programs with different levels of content of 3D anatomy knowledge and technical skills. The hypothesis was that the choice of residency program is related to spatial abilities. A cohort of 210 medical graduates was enrolled in a prospective study in a 5-year experiment. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Test (MRT) in two (MRTA) and three (MRTC) dimensions. Medical graduates were enrolled in Family Medicine (n = 76, 36.2%), Internal Medicine (64, 30.5%), Surgery (52, 24.8%), and Anesthesia (18, 8.6%). The assumption was that the level of 3D anatomy knowledge and technical skills content was higher in Surgery and Anesthesia compared to Family Medicine and Internal Medicine. Mean MRTA score of 12.4 (±SD 4.6), 12.0 (±4.3), 14.1 (±4.3), and 14.6 (±4.0) was obtained in Family Medicine, Internal Medicine, Surgery, and Anesthesia, respectively (P = 0.0176). Similarly, mean MRTC score of 8.0 (±4.4), 7.5 (±3.6), 8.5 (±3.9), and 7.9 (±4.1) was obtained (P = 0.5647). Although there was a tendency for lower MRTA score in Family Medicine and Internal Medicine compared to Surgery and Anesthesia, no statistically significant main effect of residency, year, sex, or the interactions were observed for the MRTA and MRTC. Studied sample of medical graduates was not found to choose their residency programs based on their innate spatial abilities.

10.1002/ase.1453

pubmed_125_9776

PURPOSE Recent data indicate that extended dosing intervals (EDIs) with lanreotide autogel 120 mg are effective and well-received among patients with acromegaly who have achieved biochemical control with monthly injections of long-acting somatostatin analogues (SSAs). We further evaluated the effectiveness of lanreotide autogel 120 mg delivered at EDIs (>4 weeks) in routine clinical practice. METHODS Cross-sectional, multicentre, observational study conducted to determine the effectiveness-measured by control of serum insulin-like growth factor 1 (IGF-1)-of lanreotide autogel 120 mg at dosing intervals >4 weeks for ≥6 months in selected patients with acromegaly treated in routine clinical practice (NCT02807233). Secondary assessments included control of growth hormone (GH) levels, treatment adherence, patient satisfaction, and quality of life (QoL) using validated questionnaires (EQ-5D, AcroQoL, and TSQM-9). Patients who received radiotherapy within the last 6 months were excluded. RESULTS Among 109 patients evaluated, mean (SD) age was 59.1 (13.2) years. IGF-1 values were normal (mean [SD]: 175.0 [74.5], 95% CI: 160.8 -189.1) in 91.7% of cases and normal in 91.4% of patients without previous radiotherapy treatment (n = 81). GH levels were ≤2.5 and ≤1 ng/mL, respectively, in 80.6% and 58.3%. Most patients were treated either every 5-6 (57.8%) or 7-8 weeks (38.5%), with 2.8% treated greater than every 8 weeks. The mean AcroQoL score was 63.0 (20.1). The mean global treatment satisfaction score (TSQM-9) was 75.1 (16.6). Treatment adherence (defined as no missed injections) was 94.5%. CONCLUSION Lanreotide autogel 120 mg at intervals of >4 weeks provided IGF-1 control in more than 90% of patients with acromegaly. Treatment satisfaction and adherence were good. These findings support use of extended dosing intervals in patients who have achieved good biochemical control with long-acting SSAs.

10.1007/s12020-020-02424-z

pubmed_126_488

Many human cancers are caused by synthetic or natural chemical compounds in the environment. Esophageal squamous cell carcinoma has been reported to be epidemiologically associated with tobacco and alcohol consumption. We studied the association between genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and esophageal squamous cell carcinoma susceptibility. We examined genetic polymorphisms of the CYPIA1, GSTM1, CYPIIE1, ADH2, and ALDH2 genes in 94 Japanese patients with esophageal squamous cell carcinoma and 70 unrelated healthy Japanese persons. There were no significant differences between healthy controls and patients with esophageal cancer in the polymorphisms of the CYPIA1, GSTM1, and CYPIIE1 genes. On the other hand, there were significant differences in the ADH2 and ALDH2 polymorphisms between healthy controls and esophageal cancer patients. The ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) genotypes were independently and significantly higher in esophageal cancer patients than in healthy controls. Furthermore, persons with the combined genotypes ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) were at extraordinarily high risk for esophageal squamous cell carcinoma, with an odds ratio of 17.9 (p < 0.001). Thus polymorphisms of alcohol-metabolizing enzymes, that is, ADH2 and ALDH2, may be useful for screening patients at high risk for esophageal cancer, which might facilitate clarification of esophageal tumorigenesis and prevention of esophageal cancer.

10.1097/00004836-199712000-00003

pubmed_59_1253

Aquantitative trait locus (QTL) for blood pressure was previously detected on rat chromosome 10 (RNO10) by linkage analysis and confirmed by the construction of congenic strains that encompass large regions of RNO10. In the present study, the rat RNO10 blood pressure QTL was dissected by the further construction of congenic substrains. The original congenic region was shown to contain 2 blood pressure QTLs (QTL 1 and QTL 2) approximately 24 cM apart. These were localized to a <2.6-cM region between markers D10Rat27 and D10Rat24 for QTL 1 and to a <3.2-cM region between D10Rat12 and D10Mco70 for QTL 2. Comparative mapping suggests that the rat RNO10 QTL 2 could be localized very close to a blood pressure QTL described by sib-pair analysis on human chromosome 17, but this is not definitively established because of multiple and complex chromosomal rearrangements between rodents and humans.

10.1161/hy1001.091503

pubmed_768_18527

OBJECTIVE Traditional operation frequently depends on experience of doctors and anatomic landmark visual observation, which often leads to deviation in acetabular prosthesis implantation. Computer navigation technique greatly improves accuracy of prosthesis implantation. The present meta-analysis aimed at assessing the accuracy and clinical significance of computer navigation for acetabular implantation. METHODS All studies published through March 2013 were systematically searched from PubMed, EMBnse, Science Direct, Cechrane library and other databases. Relevant journals or conference proceedings were searched manually. Only randomized controlled trials (RCTs) were included. Two independent reviewers identified and assessed the literature. Mean difference (MD) and Odds ratio (OR) of radiologic and clinical outcomes were pooled throughout the study between navigated and conventional THA. The meta-analysis was conducted by RevMan 5.1 software. RESULTS Thirteen studies were included in the review, with a total sample size of 1071 hips. Statistically significant differences were observed between navigated and conventional groups in the number of acetabular cups implanted beyond the safe zone [OR = 0.13, 95% confidence interval (CI) (0.08-0.22); P < 0.00001], operative time [MD = 19.87 min, 95% CI (14.04-24.35); P < 0.00001] and leg length discrepancy [MD = -4.16 mm, 95% CI (-7.74 to -1.48); P = 0.004]. No significant differences in cup inclination, anteversion, incidence of postoperative dislocation or deep vein thrombosis were found. CONCLUSIONS The present meta-analysis indicated that the use of computer navigation in patients undergoing THA improves the precision of acetabular cup placement by decreasing the number of outliers, and decreases leg length discrepancy. More high quality RCTs are required to further confirm our results.

pubmed_768_18527

pubmed_100_24215

OBJECTIVES This article investigated factors associated with internet usage in the Swedish older adults ranging in age from 60 to 96. Personality traits and individual characteristics have been previously noted to influence internet usage, where older adults have not been the focus population. In this study, the relationships between personality, individual characteristics and internet usage were investigated. METHODS A descriptive analysis of the personality tests of a total of 1402 subjects included in the Swedish National Study on Aging and Care was conducted. Three variables were controlled for: sex, age and education. Descriptive statistics, Mann-Whitney and Kruskal-Wallis tests, chi-square tests and a logistic regression were used in order to detect the relationships with internet usage. RESULTS Men differ significantly from women in the personality traits analysis. Those with higher education were more open and neuroticism was lower in the oldest older adults. Internet usage declined significantly with age and those with middle to higher education were using the internet the most. No other associations with internet use were found. CONCLUSION Personality traits and individual characteristics do not seem to influence the Swedish older adult and their internet usage. What one needs to account for is the age and education of the person. The more educated and the youngest cohorts were using the internet more frequently.

10.1080/13607863.2011.602958

pubmed_1013_8634

Electrooculogram (EOG) is a well-known physiological metric picked up by placing two or more electrodes around the eyeball. EOG signals are known to be extremely susceptible to motion artifacts. This paper presents a single channel, wireless, wearable flexible EOG monitoring system with motion artifacts sensing and reduction feature. The system uses two non-contact electrode pairs for EOG/motion artifacts detection and motion artifacts reduction. It is implemented on a four-layer flexible polyimide substrate. It is light-weight (only 8.75 gram), battery operated, and uses a microcontroller and a BLE 5.0 transceiver for wireless EOG data transmission, while consuming only 56 mW of power. The system metrics such as gain around 37 dB, bandwidth from 1 Hz to 40 Hz, and noise are evaluated. The system is tested for different electrode configurations and it is demonstrated that horizontally parallel electrode pairs achieve an acceptable motion artifact reduction at the output, while preserving perfect EOG features (such as eye-blinking). The average sensitivity for horizontally parallel non-contact electrodes is found out to be more than 50 times with respect to commercial gold electrodes, whereas the average response time of the sensor is around 380 mS. The flexible EOG system is comfortable to wear and the use of non-contact electrode eliminates the need of skin preparation. Therefore, the system can be easily integrated with eye-masks and headbands, thus making it an excellent prototype for many smart applications.

10.1109/TBCAS.2022.3168236

pubmed_525_12557

The rocG gene of Bacillus subtilis, encoding a catabolic glutamate dehydrogenase, is transcribed by SigL (sigma(54))-containing RNA polymerase and requires for its expression RocR, a member of the NtrC/NifA family of proteins that bind to enhancer-like elements, called upstream activating sequences (UAS). Unlike the case for other sigma(54)-dependent genes, rocG has no UAS; instead, its expression depends on a sequence located 1.5 kilobases downstream of the rocG promoter, beyond the end of the rocG coding region. The same sequence also serves as the UAS for the downstream rocABC operon and can activate rocG if moved upstream of its promoter. Furthermore, the activating sequence can be moved as far as 15 kilobases downstream of the rocG promoter and still retain partial activity.

10.1073/pnas.96.18.10290

pubmed_392_14370

BACKGROUND Ocular Myasthenia Gravis (OMG) is an autoimmune disease which causes ptosis, diplopia, or both. There is very limited information on the presenting symptoms, treatment trends, factors influencing generalization, and treatment outcome in Thai populations. OBJECTIVE To investigate characteristics of the presenting symptoms, associated factors for conversion to Generalized-MG (GMG), and treatment outcome in OMG patients. METHODS We analyzed data from patients diagnosed with OMG between January 2015 and December 2020 at Rajavithi Hospital, Thailand. We investigated disease generalization in time-to-event analysis and compared factors associated with disease generalization using a Cox-proportional-hazards model. RESULTS Of the 155 consecutive patients, 106 (68.4%) were female and their mean (SD) age was 49.3 years (15.51). There were 123 (79.35%) and 32 (20.6%) patients in the remained OMG and GMG groups respectively. Ptosis was the presenting symptom in 147 (94.8%) patients, diplopia alone was found in 8 (5.2%), and both symptoms were present in 53 (34.2%) patients. GMG patients had a higher proportion of combined ptosis and diplopia (p = 0.01), and positive AChR-Antibody test (p = 0.013). Overall, 32 (20.65%) patients converted to GMG, mostly in the first 48 months. Multivariate Cox-proportional-hazard model identified positive AChR-Ab test as a risk factor for generalization (HR, 5.32, 95% CI; 1.02-27.84). CONCLUSIONS The conversion rate to GMG in our study was 20.65%. The presence of AChR-Ab was identified as a risk factor for generalization of the disease; therefore, patients with OMG should be advised to test for AChR-Ab for both diagnosis and prognosis purpose.

10.12932/AP-260521-1141

pubmed_1125_18625

BACKGROUND Situation awareness (SA) is defined as the perception of elements in the environment within a volume of time and space, the comprehension of their meaning, and the projection of their status in the near future. This construct is vital to decision making in intense, dynamic environments. It has been used in aviation as it relates to pilot performance, but has not been applied to medical education. The most widely used objective tool for measuring trainee SA is the Situation Awareness Global Assessment Technique (SAGAT). The purpose of this study was to design and validate SAGAT for assessment of practical trauma skills, and to compare SAGAT results to traditional checklist style scoring. METHODS Using the Human Patient Simulator, we designed SAGAT for practical trauma skills assessment based on Advanced Trauma Life Support objectives. Sixteen subjects (four staff surgeons, four senior residents, four junior residents, and four medical students) participated in three scenarios each. They were assessed using SAGAT and traditional checklist assessment. A questionnaire was used to assess possible confounding factors in attaining SA and overall trainee satisfaction. RESULTS SAGAT was found to show significant difference (analysis of variance; p < 0.001) in scores based on level of training lending statistical support to construct validity. SAGAT was likewise found to display reliability (Cronbach's alpha 0.767), and significant scoring correlation with traditional checklist performance measures (Pearson's coefficient 0.806). The questionnaire revealed no confounding factors and universal satisfaction with the human patient simulator and SAGAT. CONCLUSIONS SAGAT is a valid, reliable assessment tool for trauma trainees in the dynamic clinical environment created by human patient simulation. Information provided by SAGAT could provide specific feedback, direct individualized teaching, and support curriculum change. Introduction of SAGAT could improve the current assessment model for practical trauma education.

10.1097/01.ta.0000238687.23622.89

pubmed_509_9534

A novel gram-negative, rod-shaped, non-motile, psychrophilic bacterium, designated strain E4-9a(T), was isolated from a marine sediment sample collected at a depth of 276 m from Kongsfjorden, Svalbard, in the Arctic Ocean. The colony colour was golden yellow. Strain E4-9a(T) was positive for amylase activity at 5 °C. The predominant fatty acids were iso-C(15 : 1) G (21.8 %), anteiso-C(15 : 0) (19.1 %), anteiso-C(15 : 1) A (18.6 %), iso-C(15 : 0) (13.8 %) and iso-C(16 : 1) H (6.4 %). Strain E4-9a(T) contained MK-6 as the major respiratory quinone. The polar lipids consisted of phosphatidylethanolamine, three unidentified aminolipids (AL1, AL4 and AL5), an unidentified phospholipid and four unidentified lipids (L1, L4 to L6). Based on 16S rRNA gene sequence similarity, it was ascertained that the closest related species to E4-9a(T) were Lacinutrix copepodicola, L. algicola and L. mariniflava, with sequence similarity to the respective type strains of 98.5, 96.5 and 95.8 %. Phylogenetic analysis showed that strain E4-9a(T) clustered with the type strain of L. copepodicola and with those of L. algicola and L. mariniflava at distances of 1.5 and 4.8 % (98.5 and 95.2 % similarity), respectively. However, DNA-DNA hybridization with L. copepodicola DJ3(T) showed 59 % relatedness with respect to strain E4-9a(T). The DNA G+C content of strain E4-9a(T) was 29 mol%. Based on the results of DNA-DNA hybridization and phenotypic data, it appears that strain E4-9a(T) represents a novel species of the genus Lacinutrix, for which the name Lacinutrix himadriensis sp. nov. is proposed. The type strain is E4-9a(T) ( = CIP 110310(T)  = KCTC 23612(T)).

10.1099/ijs.0.040907-0

pubmed_181_7455

PURPOSE: To compared the effects of sevoflurane and desflurane on early anesthesia recovery in patients undergoing to craniotomy for intracranial lesions. METHODS: After IRB approval, the study included 50 patients aged 18-70 years who had ASA physical statuses of I-II and were scheduled for intracranial surgery. Patients were randomly divided into two groups: sevoflurane and desflurane. Anaesthesia was routinely induced in all patients followed by desflurane 5%-6% or sevoflurane 1%-2%. Moreover remifentanil infusion (0.05-0.2 mcg/kg/min) was adjusted to maintain mean arterial pressure (MAP) within 20% baseline and heart rate <90 bpm. Postoperatively, patients were evaluated over time for responses to painful stimulus, eye opening, hand squeezing, extubation, orientation and time required to achieve a Modified Aldrete Score of 9-10. Parametric and non-parametric data were assessed using Student's t- and Mann-Whitney U tests, respectively. A p<0.05 was taken as statistically significant. RESULTS: The times to responses to painful stimuli (7.7±2.7 vs. 4.8±1.7 min.; p<0.001), emergence (9.5±2.81 vs. 6.3±2.2 min.; p<0.001), hand-squeezing (12.1±2.9 vs. 8.2±2.3 min.; p<0.001), extubation (10.1±2.87 vs. 7.1±1.6 min.; p<0.001), orientation (15.3±3.2 vs. 10.3±2.7 min.; p<0.001) and Aldrete score of 9-10 (23.3±6.1 vs. 15.8±3.8 min.; p<0.001) were significantly lower with desflurane-based anaesthesia vs. sevoflurane-based anaesthesia. CONCLUSION: Desflurane yields early recovery functions and facilitates early postoperative neurologic examinations of intracranial surgery patients.

10.1590/S0102-865020160090000010

pubmed_215_21534

Two-action tests of imitation compare groups that observe topographically different responses to a common manipulandum. The general aim of the two experiments reported here was to find a demonstrator-consistent responding effect in a procedure that could be elaborated to investigate aspects of what was learned about the demonstrated lever response. Experiment 1 was a pilot study with rats of a variant of the two-action method of investigating social learning about observed responses. Groups of observer rats ( Rattus norvegicus) saw a demonstrator push a lever up or down for a food reward. When these observers were subsequently given access to the lever and rewarded for responses in both directions, their directional preferences were compared with two 'screen control' groups that were unable to see their demonstrators' behaviour. Demonstrator-consistent responding was found to be restricted to observers that were able to see demonstrator performance, suggesting that scent cues alone were insufficient to cue a preference for the demonstrators' response direction and thereby that the rats learned by observation about body movements (imitation) or lever movement (emulation). Experiment 2 assessed responding on two levers, one that had been manipulated by the demonstrator, and a second, transposed lever positioned some distance away. Demonstrator-consistent responding was abolished when actions were observed and performed in different parts of the apparatus, suggesting that observed movement was encoded allocentrically with respect to the apparatus rather than egocentrically with respect to the actor's body. With particular reference to the influence of scent cues, the results are discussed in relation to the strengths and weaknesses of this and other varieties of the two-action procedure as tests of imitation in animals and human infants.

10.1007/s10071-002-0154-7

pubmed_807_23723

Since its introduction five decades ago, free-flow electrophoresis (FFE) has been mainly employed for the isolation and fractionation of cells, cell organelles and protein mixtures. In the meantime, the growing interest in the proteome of these bio-particles and biopolymers has shed light on two further facets in the potential of FFE, namely its applicability as an analytical tool and sensor. This review is intended to outline recent innovations, FFE has gained in the proteomic era, and to point out the valuable contributions it has made to the analysis of the proteome of cells, sub-cellular organelles and functional protein networks.

10.1002/elps.200900771

pubmed_335_25652

Contrast reagents for ultrasound imaging are widely used in clinical medical diagnosis because ultrasound resolution is limited. Contrast agents must be utilized to enhance the image resolution. At present, microbubbles (MBs) and nanobubbles (NBs) are the main contrast reagent candidates for improving the signal resolution. Fluorescence upconversion nanoparticles provide high sensitivity and also function as nanocarriers. This can label tumor cells in a specific organ under irradiation of near-infrared (NIR) light. However, despite the use of NIR light, the penetration depth of NIR is only approximately 15 mm. Thus, we combine fluorescence with ultrasonic imaging to achieve the effect of multiple imaging and solve the low penetration depth of fluorescence imaging and the poor resolution of ultrasound imaging. The dual imaging modalities achieved higher resolution or signal to noise ratios. In this study, Nd3+-sensitized upconversion nanoparticles (UCNPs) are combined with graphitic carbon nitride quantum dots (CNs) and embedded in NBs (UCNP-CN@NBs). The UCNPs are excited by 808 nm light and emit visible and ultraviolet light. Then, the energy of the ultraviolet light is transferred to the CNs to produce reactive oxygen species (ROS) for photodynamic therapy. Ultrasonic waves are also used to promote NB bursting and the release of ROS molecules in photodynamic therapy, leading to cancer cell apoptosis.

10.1039/c8sc00108a

others_413_29361

Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. The sequestration of parasitized erythrocytes in the microvasculature of vital organs is a central pathophysiological feature. The plasma concentration of the parasite protein P. falciparum Histidine-Rich Protein 2 (PfHRP2) has diagnostic and prognostic value in severe malaria. In the current study we investigate the potential use of plasma PfHRP2 and the sequestration index (the ratio of plasma PfHRP2 to circulating parasites) as quantitative traits in the conduct of case-only genetic association studies of severe malaria. We demonstrate the utility of this approach using data from over 2,000 Kenyan children with severe malaria, genotyped for 14 major candidate genes that were found to be associated with protection against severe malaria in previous studies. We show that PfHRP2 is a more informative quantitative trait than peripheral parasite density, and that polymorphisms in four major red cell genes (the {beta}S sickle mutation in HBB, the blood group mutation O in ABO, the -thalassaemia mutation in HBA, and the Dantu blood group mutation in GYP) are associated with substantially lower concentrations of plasma PfHRP2 at admission. Further, the effect sizes we observed were considerably larger than those relating to peripheral parasite density. An unexpected outlier was the rs1541255 A>G polymorphism in ATP2B4 for which we saw higher plasma PfHRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for how this might be explained in the context of this specific protective allel

10.1101/2022.02.21.22271267

pubmed_359_4931

OBJECTIVES Aspirated objects generally represent items accessible to children. When metallic candy wrapper aspiration is questioned, radiographic studies may aid diagnosis. An infant with repeated chest radiographs negative for a metallic foreign body was found to have a multi-layer metallic candy wrapper in the left main bronchus. The purpose of this study was to determine whether conventional and dual-energy radiographic techniques exclude the presence of aspirated metallic foil wrappers. METHODS Single-layer and multi-layer metallic candy wrappers were radiographically studied with conventional and dual-energy radiographic techniques in 3 tissue models. RESULTS No single-layer metallic samples were detectable with conventional or dual-energy radiography. The multilayer samples were not detectable at less than 8 layers (pulmonary tissue model) or 16 layers (mediastinal model) by either conventional or dual-energy radiography. CONCLUSIONS Conventional and dual-energy chest radiographic techniques do not reliably exclude the presence of aspirated metallic foil wrappers.

10.1177/000348940511400601

pubmed_207_18432

The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, inasmuch as it may allow tumors to escape immune surveillance. We have observed reduced expression of HLA antigens in sporadic colon cancer and adenomas from familial adenomatous polyposis patients. We now studied the expression of HLA class I antigens in patients with sporadic adenomas, which are precursors of colorectal cancer. Expression of HLA class I antigens was studied by immunohistochemistry in (a) sporadic colon adenomas, (b) histologically normal mucosa distant from the adenomas, (c) histologically normal colonic mucosa from patients with history of sporadic colon adenomas, and (d) colonic mucosa from normal subjects. HLA class I antigen expression was moderately reduced in 56% and severely reduced in 44% of the adenomas; this reduction was significant when compared to controls (P < 0.0001). The reduction of HLA class I expression in adenomas was related to the grade of dysplasia of the adenomas. HLA class I expression of normal appearing mucosa was decreased in 76% of patients with adenoma (P < 0.0001) and in 54% of patients with history of adenoma (P < 0.005) compared to normal controls. These changes were antigen specific, inasmuch as the expression of carcinoembryonic antigen, a surface antigen, was not affected. Our findings suggest that reduced HLA class I expression is an early event in the cell transformation process from normal to neoplastic state, preceding in many cases the onset of histological changes. HLA class I could be potentially used as a premalignant marker in the colon.

pubmed_207_18432

pubmed_391_13737

In the present study a newly formulated dialysis solution (HDF) was tested for its effects on phagocyte viability and function as well as its ability to support bacterial growth. This solution differs from standard CAPD solution (NPD) by the inclusion of histidine to buffer the fluid to pH 6.7. Low-dextrose HDF (1.36% w/v dextrose) did not significantly decrease the viability or inhibit any of the PMN functional parameters measured (phagocytosis, LTB4 release or respiratory burst activation) when compared to control buffer. NPD (1.36% w/v dextrose) at low pH as well as all high-dextrose dialysis solutions (NPD and HDF) significantly inhibited most PMN functions independently of reduced viability. Peritoneal mesothelial cell viability was unaffected by either low- or high-dextrose HDF but was significantly reduced by NPD (1.36 and 3.86% dextrose) at pH 5.2. The inhibitory effects of low dextrose dialysis solutions were confirmed as being partly related to their low initial pH. High-dextrose dialysis fluids, however, inhibit PMN function by a mechanism which, in addition to initial pH, appears to be directly related to their dextrose content but not their osmolality.

10.1093/ndt/6.8.574

pubmed_1066_2968

Respiratory pathogens such as Chlamydia pneumoniae may activate osteoclast cells, thereby inducing bone resorption and joint inflammation. Herein is a case report of a young man with misdiagnosed persistent wrist pain without any major trauma. Investigation of the patient's medical history confirmed a recent systemic C. pneumoniae infection. Preoperative X-ray and magnetic resonance imaging (MRI) showed a substantial decrease in cancellous lunate bone compactness. A stepwise approach was undertaken considering the rapid onset of bone devascularisation and the clinical presentation. Wrist arthroscopy confirmed extensive joint inflammation associated with decreased osteochondral lunate solidity. Microbiological examination excluded joint infection. Histological analysis showed a diffuse inflammatory infiltration. Temporary mediocarpal K-wire stabilization and synovectomy were performed. Postoperative MRI confirmed lunate bone revascularization. At 6 and 12 months' follow-up the young man was pain-free and had good recovery of range of motion. In vitro and in vivo studies demonstrate that inflammatory conditions may promote osteoclast cell activity and induce bone resorption. Moreover, infection with C. pneumoniae could activate specific "osteoporotic" bone pathways. To the authors' knowledge, this is the first published case report of specific lunate bone loss induced by systemic C. pneumoniae infection. The authors proposed an etiologic explanation, and a stepwise approach was associated with good outcome.

10.1016/j.tcr.2021.100431

pubmed_73_24354

Superior mesenteric artery (SMA) syndrome describes vascular compression of the third portion of the duodenum and presents with nausea, postprandial vomiting, and epigastric abdominal pain. The syndrome is rare and may be missed if appropriate radiologic studies are not performed or the clinical presentation is atypical. The clinical contexts in which SMA syndrome develops usually involve rapid weight loss, alterations in spine anatomy, or external increases in abdominal pressure. Diagnostic methods for identifying duodenal obstruction by the SMA include upper gastrointestinal barium contrast studies, computed tomography scans, or angiography of the aorta with either contrast or magnetic resonance angiography. Medical therapy relies upon nutritional rehabilitation with either jejunal tube feedings or parenteral nutrition until weight gain results in relief of the obstruction. In instances where this approach fails, surgical correction is necessary, most often with laparoscopic duodenojejunostomy.

10.1097/MOP.0b013e32833c4947