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Aroma extract dilution analysis of Cv. Marion (Rubus spp. hyb) and Cv. Evergreen (R. laciniatus L.) blackberries. Cultivar Marion and Evergreen blackberry aromas were analyzed by aroma extract dilution analysis. Sixty-three aromas were identified (some tentatively) by mass spectrometry and gas chromatography-retention time; 48 were common to both cultivars, and 27 have not been previously reported in blackberry fruit. A comparison of cultivars shows that both have comparable compound types and numbers but with widely differing aroma impacts, as measured by flavor dilution (FD) factors. Ethyl 2-methylbutanoate, ethyl 2-methylpropanoate, hexanal, furanones (2,5-dimethyl-4-hydroxy-3-(2H)-furanone, 2-ethyl-4-hydroxy-5-methyl-3-(2H)-furanone, 4-hydroxy-5-methyl-3-(2H)-furanone, 4,5-dimethyl-3-hydroxy-2-(5H)-furanone, and 5-ethyl-3-hydroxy-4-methyl-2-(5H)-furanone), and sulfur compounds (thiophene, dimethyl sulfide, dimethyl disulfide, dimethyl trisulfide, 2-methylthiophene, and methional) were prominent in Evergreen (FD 512-2048). Except for ethyl 2-methylpropanoate, these same compounds were also prominent in Marion, but the FD factors varied significantly (FD 8-256) from Evergreen. The aroma profile of blackberry is complex, as no single volatile was unanimously described as characteristically blackberry.

Cross-reactivity between Bacillus Calmette-Guérin and Rous Virus-induced sarcoma detected in rats by tube leukocyte adherence inhibition assay. Specific immunity to Rous virus-induced sarcoma (RSL) was investigated by the tube leukocyte adherence inhibition (LAI) assay in rats immunized with Bacillus Calmette-Guérin (BCG). Peritoneal cells from Lewis rats immunized s.c. with BCG gave positive reactions in the tube LAI assay with the antigen prepared from RSL in Lewis rats. Lymph node cells from Lewis rats immunized with BCG had no cytotoxic effect on RSL cells in vitro, whereas peritoneal cells from the same rats were strongly cytotoxic for RSL cells. Growth of RSL tumors in vivo was not inhibited in BCG-treated rats as compared to that in untreated rats. The results show that LAI reactivity correlates with cytotoxicity of peritoneal cells and does not correlate with the cytotoxicity of lymph node cells and that positive LAI reactions with tumor antigen need not be reflected in the suppression of growth of the tumor in vivo.

The algorithms of adjuvant therapy in gliomas and their effect on survival. The treatment of gliomas became more sophisticated during the last decades. As by now, adjuvant treatment after maximum safe resection is considered an important and effective treatment strategy in most gliomas, yet the decision is based on several factors. This review summarizes the available evidence for the current adjuvant treatment algorithms with a focus on the impact on the survival of glioma patients. The review is based on the current guidelines, but it also includes new insights which have not yet been included into the official guidelines.

The Anaform endoprosthesis: a proplast-coated femoral endoprosthesis. The Anaform endoprosthesis study is a prospective trial by 12 orthopedic surgeons from six different hospitals in the Netherlands begun September 1984. As of March 1, 1988, 510 prostheses had been implanted, 60 with a follow up of more than 3 years. Of the 181 patients with a follow up of more than 2 years, 92% had a Harris hip score of more than 80 points. Apart from the main series, the prosthesis was used in 35 patients for revision of a cemented prosthesis, of whom 13 had a follow up of more than 2 years. Of these, ten patients (73%) had a Harris hip score of more than 80 points. Most patients studied were more than 65 years old. Fixation by ingrowth of fibrous tissue in a 2 mm thick, soft, flexible, low-modulus stem coating can provide painless function, clinical stabilization, and normal gait. The Anaform femoral endoprosthesis seems to be of advantage in the young patient as a method of cementless fixation. When necessary, removal without bone destruction is easy.

Hepatobiliary diseases and insulin resistance. In recent years, there has been an increasing prevalence of obesity and related diseases. This epidemiological change has increased the interest of researchers in the molecular and biochemical pathways involved in the pathogenesis of hepatic and biliary diseases. Insulin resistance is considered the major mechanism involved in the hepatic and biliary manifestations of obesity. Epidemiological, clinical, and basic research demonstrates that insulin resistance is associated with gallstone disease, nonalcoholic fatty liver disease, and poor outcomes in viral hepatitis C treatments. Fascinating experimental evidence demonstrates that fat-induced hepatic insulin resistance may result from the activation of kinases leading to impaired insulin signaling. The insulin-resistant state is characterized by a failure to suppress hepatic glucose production and glycogenolysis, with enhanced fat accumulation in hepatocytes because of increased lipolysis, increased free fatty acid uptake by hepatocytes, and increased hepatic synthesis of triglycerides. This molecular signaling induces a low-grade chronic inflammatory state, characterized by increased levels of proinflammatory molecules and acute-phase proteins. This review summarizes the most important molecular and biochemical issues in the hepatic and biliary diseases associated with insulin resistance.

A comparison of three geographical isolates of Trichinella spiralis from the mid-Atlantic United States. Three isolates of Trichinella spiralis (black bear: 41o50'N, 79o00'W, 1982; grey fox: 41o00'N, 76o00'W, 1982; domestic pig: 39o80'N, 75o30'W, 1983) from the mid-Atlantic United States were characterized in Crl: COBS CFW (SW) mice during 10 successive 40-day generations. Over 10 generations, the isolates differed as follows: worm position of the ursine isolate was significantly more posteriad compared to the porcine isolate; sex ratio of the vulpine isolate was significantly lower compared to the ursine and porcine isolates; females of the porcine isolate produced significantly more newborn larvae in vitro than the sylvatic isolates; both the larvae per gram (LPG) and reproductive capacity index (RCI) were significantly higher for the porcine isolate; and male worms of the vulpine isolate were significantly smaller than those of the porcine or ursine isolates. No differences were observed among isolates for percentage of inoculum recovered, length of female worms, or uterine length. The fecundity of the isolates in hamsters, gerbils, multimammate rats, Sprague-Dawley rats, and Peromyscus sp. was examined also. Based upon RCI and LPG, the porcine isolate was the most fecund in all hosts except gerbils. This higher fecundity was often manifest as increased morbidity and mortality in hosts infected with this isolate. The relationship between the virulent nature of the porcine isolate and the enhanced transmission of T. spiralis are discussed.

[The formation of the deviant behavior in adolescents (psychopathological and psychological aspects)]. Psychopathological manifestations of deviant behavior, self-estimation psychological characteristics and accentuation of the personality were studied in 180 girls aged 12-17 years with deviant and 80 girls with normal behavior. 5 psychopathological variants of deviant behavior were singled out: psychopath-like, psychopath-like with hysteric episodes, asthenic, astheno-depressive, astheno-neurotic with hysteric episodes. The notion "total deviation" is introduced which allow to define the level of deviant disorders.

Search for CP Violation and Measurement of the Branching Fraction in the Decay D^{0}→K_{S}^{0}K_{S}^{0}. We report a study of the decay D^{0}→K_{S}^{0}K_{S}^{0} using 921 fb^{-1} of data collected at or near the ϒ(4S) and ϒ(5S) resonances with the Belle detector at the KEKB asymmetric energy e^{+}e^{-} collider. The measured time-integrated CP asymmetry is A_{CP}(D^{0}→K_{S}^{0}K_{S}^{0})=(-0.02±1.53±0.02±0.17)%, and the branching fraction is B(D^{0}→K_{S}^{0}K_{S}^{0})=(1.321±0.023±0.036±0.044)×10^{-4}, where the first uncertainty is statistical, the second is systematic, and the third is due to the normalization mode (D^{0}→K_{S}^{0}π^{0}). These results are significantly more precise than previous measurements available for this mode. The A_{CP} measurement is consistent with the standard model expectation.

Lipid storage myopathy in Kearns-Sayre syndrome. A 7-year-old girl had external ophthalmoplegia, limb weakness, short stature, hearing loss, pigmentary degeneration of the retina, and increased CSF protein content. Muscle biopsy revealed vacuolar myopathy with accumulation of lipids. Electronmicroscopy showed abnormalities of shape, size, and internal structure of muscle mitochondria. Muscle activity of palmitoyl-CoA synthetase was decreased, and the content of lipids was increased. Serum and muscle carnitine levels were normal, as were muscle carnitine palmitoyltransferase and carnitine acetyltransferase.

Assessment of Fluid Balance and the Approach to Fluid Therapy in the Perioperative Patient. Perioperative patients can be highly dynamic and have various metabolic, physiologic, and organ system derangements that necessitate smart monitoring strategies and careful fluid therapy. The interplay between changing patient status, therapeutic interventions, and patient response makes effective monitoring crucial to successful treatment. Monitoring the perioperative patient and an approach to fluid therapy are discussed in this text.

Three-dimensional ultrasonography of normal fetal heart: comparison with two-dimensional imaging. Thirty-one high-risk patients (16 to 35 weeks' gestation) underwent two-dimensional and three-dimensional ultrasonography to compare two-dimensional and non-cardiac-gated three-dimensional ultrasonography of the normal fetal heart. After normal two-dimensional studies, three-dimensional sonographic volumes were acquired without cardiac gating in transverse and longitudinal planes. Standard cardiac views were derived from three-dimensional data, analyzed, and rated as follows: (1) not identifiable, (2) identifiable but inadequate for diagnosis, (3) adequate, and (4) excellent. Two-dimensional ultrasonography demonstrated better yields of diagnostically acceptable images of basic echocardiographic views (four-chamber view, 100% for two-dimensional sonography versus 10 to 71% for three-dimensional sonography; right ventricular outflow tract, 42% for two-dimensional versus 6 to 26% for three-dimensional ultrasonography; left ventricular outflow tract, 71% for two-dimensional versus 13 to 45% for three-dimensional sonography). In one subject three-dimensional ultrasonography was superior to two-dimensional sonography in demonstrating an outflow tract. Aortic and ductal arches were not imaged with the two-dimensional technique but were available from the acquired three-dimensional volumes in 3 to 32% and 23%, respectively. False-positive and false-negative findings were observed on three-dimensional ultrasonograms. Overall, compared to two-dimensional ultrasonography, non-cardiac-gated three-dimensional sonography yielded inadequate reconstructed image quality of basic echocardiographic views (four-chamber view, right ventricular outflow tract, left ventricular outflow tract). Three-dimensional ultrasonography, however, shows potential for allowing nonechocardiographers to acquire some diagnostically acceptable views of the aortic and ductal arches.

Hyperphosphataemia in 2019: have we made progress? This review describes recent developments in the management of serum phosphate in dialysis patients, with a focus on the development of recent trials which randomize patients to different levels of control. We review the uncertainties around clinical benefits of serum phosphate control and alternative approaches to current management, as well as a multinational attempt to conduct randomized controlled trials in this area. We discuss novel methods of limiting oral phosphate absorption. Although numerous guidelines and target ranges for serum phosphate management exist, they are largely based on observational data and there is no definitive evidence that good control improves the length or quality of life of dialysis patients. New phosphate binders continue to appear on the market with increasing financial cost but without additional meaningful outcome data. Two recently published trials have demonstrated the feasibility of a large-scale study of differing phosphate levels to test the hypothesis that reduction of serum phosphate is beneficial to dialysis patients. Restriction of oral phosphate intake should not be overlooked.

An in silico parametric model of vertebrae trabecular bone based on density and microstructural parameters to assess risk of fracture in osteoporosis. Osteoporosis is a progressive bone disease characterized by deterioration in the quantity and quality of bone, leading to inferior mechanical properties and an increased risk of fracture. Current assessment of osteoporosis is typically based on bone densitometry tools such as Quantitative Computed Tomography (QCT) and Dual Energy X-ray absorptiometry (DEXA). These assessment modalities mainly rely on estimating the bone mineral density (BMD). Hence present densitometry tools describe only the deterioration of the quantity of bone associated with the disease and not the affected morphology or microstructural changes, resulting in potential incomplete assessment, many undetected patients, and unexplained fractures. In this study, an in-silico parametric model of vertebral trabecular bone incorporating both material and microstructural parameters was developed towards the accurate assessment of osteoporosis and the consequent risk of bone fracture. The model confirms that the mechanical properties such as strength and stiffness of vertebral trabecular tissue are highly influenced by material properties as well as morphology characteristics such as connectivity, which reflects the quality of connected inter-trabecular parts. The FE cellular solid model presented here provides a holistic approach that incorporates both material and microstructural elements associated with the degenerative process, and hence has the potential to provide clinical practitioners and researchers with more accurate assessment method for the degenerative changes leading to inferior mechanical properties and increased fracture risk associated with age and/or disease such as Osteoporosis.

Calcium, calmodulin and protein kinase C dependence of platelet shape change. Platelet shape change (PSC) represents the initial phase of platelet activation and is normally investigated in ethylene diamine tetraacetic acid (EDTA) containing platelet rich plasma (PRP); EDTA is a potent chelator of calcium and therefore reduces ionized calcium to negligible levels. It is therefore assumed that it is a process independent of calcium. To test the hypothesis that PSC may be dependent upon intracellular calcium, we examined the effect of 8-(N,N-Diethylamino) octyl 3,4,5-Trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intercellular calcium mobilization on PSC. It produced a dose dependent inhibition of PSC. We then examined whether PSC was dependent upon calmodulin and protein kinase C, a calcium dependent enzyme which is cardinal to platelet aggregation. Both calmidazolium, a specific inhibitor of calmodulin, and H-9, a specific inhibitor of protein kinase C, produced dose dependent inhibition of PSC. Finally, we investigated whether GP IIb/IIIa receptor which binds fibrinogen was involved in PSC; DMP 728 [(cyclic [D-2-amino-butyryl-N2-methyl-L-arginyl-glycyl-L-aspartyl-3- (a min o-methyl-benzoic acid], methanesulfonic acid salt] a potent GP IIb/IIIa receptor antagonist was without any effect on PSC. We conclude that PSC is a calcium, calmodulin and protein kinase C dependent process like platelet aggregation but that it does not require extracellular calcium or the participation of platelet GP IIb/IIIa complex.

Immunoaffinity chromatography of human beta-hexosaminidase A. A highly specific method for the purification of human beta-hexosaminidase A employing immunoaffinity chromatography is described. Using an antiserum against the unique antigenic determinant, alpha, of beta-hexosaminidase A, and elution with 8.0M urea, a 283-or 417-fold purification of the enzyme was obtained in a single step from crude human placental homogenate.

Chemical engineering education: a gallimaufry of thoughts. To discuss various facets of chemical engineering education, I proceed step by step through my own education and career. In this way, I touch on various points concerning the operation of the educational system that may be of interest to others.

Evaluation of phosphorus adsorption capacity of sesame straw biochar on aqueous solution: influence of activation methods and pyrolysis temperatures. The phosphorus (P) adsorption characteristic of sesame straw biochar prepared with different activation agents and pyrolysis temperatures was evaluated. Between 0.109 and 0.300 mg L(-1) in the form of inorganic phosphate was released from raw sesame straw biochar in the first 1 h. The release of phosphate was significantly enhanced from 62.6 to 168.2 mg g(-1) as the pyrolysis temperature increased. Therefore, sesame straw biochar cannot be used as an adsorbent for P removal without change in the physicochemical characteristics. To increase the P adsorption of biochar in aqueous solution, various activation agents and pyrolysis temperatures were applied. The amount of P adsorbed from aqueous solution by biochar activated using different activation agents appeared in the order ZnCl2 (9.675 mg g(-1)) > MgO (8.669 mg g(-1)) ⋙ 0.1N-HCl > 0.1N-H2SO4 > K2SO4 ≥ KOH ≥ 0.1N-H3PO4, showing ZnCl2 to be the optimum activation agent. Higher P was adsorbed by the biochar activated using ZnCl2 under different pyrolysis temperatures in the order 600 °C > 500 °C > 400 °C > 300 °C. Finally, the amount of adsorbed P by activated biochar at different ratios of biochar to ZnCl2 appeared in the order 1:3 ≒ 1:1 > 3:1. As a result, the optimum ratio of biochar to ZnCl2 and pyrolysis temperature were found to be 1:1 and 600 °C for P adsorption, respectively. The maximum P adsorption capacity by activated biochar using ZnCl2 (15,460 mg kg(-1)) was higher than that of typical biochar, as determined by the Langmuir adsorption isotherm. Therefore, the ZnCl2 activation of sesame straw biochar was suitable for the preparation of activated biochar for P adsorption.

Silver containing hydrofiber dressing promotes wound healing in paediatric patients with partial thickness burns. Burn injury is one of the most common reasons for admission in paediatric population. There is currently no international consensus on the best wound dressing material. Aquacel Ag, a new silver containing hydrofiber dressing material has been reported to produce good clinical results. Yet, only a limited number of studies exist in the paediatric population. This study aims to review our experience of burn management over the past 5 years and to evaluate the effectiveness of Aquacel Ag in the management of partial thickness burns. A retrospective review of all patients admitted for burn injury between January 2010 and December 2014 was conducted. Patients' demographics, mechanism of injury, body surface areas involved, treatment applied, and clinical outcomes were analyzed. Patients with superficial injury, full thickness burns that required surgical debridement, burn area less than 2 % or more than 25 % of total body surface area, or incomplete clinical data were excluded from the comparative study. A total of 119 patients were identified. 114 (96 %) was due to domestic injury, of which 108 (91 %) was food-related. The most commonly affected areas were limbs (n = 89, 74.8 %), followed by trunk (n = 62, 74.8). 84 patients fulfilled the inclusion criteria and were recruited into the study. 31 patients received Aquacel Ag dressing and 53 patients received standard paraffin gauze dressing. The two groups showed no statistical difference in age, sex, percentage of total body surface area involved, and infection rate. Outcomes of patients treated with Aquacel Ag were compared with patients treated with standard dressing. The mean hospital stay was significantly shorter for the Aquacel Ag group (14.26 vs 23.45, p = 0.045). Aquacel Ag group required much less frequent dressing change (5.67 vs 20.59, p = 0.002). 5 patients in standard dressing group developed hypertrophic scar and required prolonged pressure garment, whereas only one hypertrophic scar was observed in the Aquacel Ag group. Aquacel Ag appears to promote early burn wound healing with less hypertrophic scar formation.

Adjuvant therapy in gastric cancer: can we prevent recurrences? Despite a dramatic decline in the incidence of gastric carcinoma in the United States during the past century, treatment remains a challenging problem for oncologists. Surgery continues to be the primary modality for managing early-stage gastric cancer, but up to 80% of patients who undergo a "curative" resection develop locoregional or distant recurrence. Given these sobering statistics, there has been great interest in developing strategies to prevent recurrences after surgery and improve overall mortality. In this article, we review data on adjuvant treatment modalities for this disease, including radiotherapy, chemotherapy, combination chemotherapy and radiation, intraperitoneal treatment, and immunotherapy. We focus attention on the recent widespread acceptance of adjuvant chemoradiotherapy, based on the results of Intergroup trial 0116. Future strategies incorporating different modalities of treatment will be outlined.

The beneficial effect on family life in treating borderline personality. The harmful effect of borderline patients on their families is an important but relatively neglected aspect of outcome studies. This study concerns changes in perceived quality of relationships with partners and children of 24 patients suffering Borderline Personality Disorder (BPD) after 12 months of treatment with the Conversational Model (CM). They were compared to 21 parents with BPD receiving "Treatment as Usual" (TAU) from their referring clinicians for the same period. Both groups developed naturalistically giving the study a quasi-experimental design. The Social Adjustment Scale (SAS-SR) was administered on intake and again after 12 months. The subscales dealing with relationships with children, with partners and with the family unit were scored and compared between groups. It was found that the perceived relationships with children and partners improved significantly for the CM group but not for the TAU group.

Pyrazoloquinoline benzodiazepine receptor ligands: effects on schedule-controlled behavior in dogs. The effects of diazepam and the pyrazoloquinoline benzodiazepine receptor ligands CGS8216, CGS9896, and CGS9895 on schedule-controlled responding were studied in dogs. Responding was maintained under a multiple fixed-interval (FI) 5-min fixed-ratio (FR) 30 response schedule of food presentation. Diazepam (PO) produced dose-related decreases in response rates under FR component. Under the FI, rates first increased and then decreased with increasing doses of diazepam. Diazepam also produced a dose-related disruption of the temporal pattern of responding under the FI as measured by decreases in quarter-life values. CGS8216 IV produced dose-related decreases in response rates under both components. The highest oral dose of CGS8216 also decreased rates in both components. CGS8216 was approximately 100 times more potent by the IV route as compared to the oral route. CGS9896 IV had no significant effect on responding under either component of the multiple schedule. However, with increasing doses of CGS9896 PO, response rates under both components first decreased and then returned to control values. CGS9895 PO was without significant effect on responding. When CGS8216 was administered concomitantly with graded doses of diazepam, the former drug blocked the rate-decreasing effects of diazepam under the FR component, but not the rate-increasing effects of diazepam under the FI. The present results demonstrate that although these three pyrazoloquinolines are benzodiazepine receptor ligands, they do not exhibit diazepam-like effects on schedule-controlled behavior.

High prevalence of three prothrombotic polymorphisms among Palestinians: factor V G1691A, factor II G20210A and methylenetetrahydrofolate reductase C677T. Factor V leiden G1691A/R506Q (FVL), prothrombin G20210A (FII) and methylenetetrahydrofolate reductase (MTHFR) C677T are related genetic risk factors for venous thromboembolism. Analysis for those mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of FVL, FII-G20210A and MTHFR-C677T polymorphisms and their coexistence among apparently healthy Palestinians. After institutional approval, 303 apparently healthy students from An-Najah University representative to North and South regions of West Bank with no previous history of cardiovascular diseases participated in this study. A uniform questionnaire was used to collect relevant information through personal interview with the subjects. The collected information included gender, age, smoking habits, weight and height, diseases such as diabetes, cardiovascular and family history of CVD. The frequencies of allelic distribution of the three prothrombotic polymorphisms factor V G1691A/R506Q), prothrombin G2010A, and MTHFR-C677T were 0.114, 0.050 and 0.071, respectively. The prevalence of the three thrombotic polymorphisms (FVL, FII G20210A and MTHFR-C677T) were 20.1, 9.1 and 13.8 %, respectively. Statistical analysis for factor V leiden showed no significant association between place of residence (P value = 0.953) and gender (P value >0.082). The data presented in this study showed the highest prevalence of FVL among healthy Palestinians compared to other populations and this important finding should be followed in terms of clinical significance.

A correlative study of RU38486 biopotency and competition with [3H]dexamethasone for receptors in the rat central nervous system. Dexamethasone inhibitory action on the release of adrenocorticotrophin has been studied using in vitro anterior pituitary preparations. This inhibition is reversed when the animal is given the antiglucocorticoid compound RU38486 simultaneously with dexamethasone. RU38486 acts at the receptor level and in the cytosolic binding study, it competes with [3H]dexamethasone for the binding sites in pituitary. Such competition is even more pronounced in hypothalamus and hippocampus, indicating that RU38486 also exert its antagonistic action at these sites.

Preventive effect of Pueraria mirifica on testosterone-induced prostatic hyperplasia in Sprague Dawley rats. Pueraria mirifica (PM) extract contains phytoestrogen daidzein and genistein. In this study, we investigated the protective effect of PM extract, daidzein and genistein on a testosterone-induced prostatic hyperplasia in rats. Testosterone was administered at 3 mg kg(-1) to rats followed by the PM extract, daidzein and genistein for a period of 30 days with finasteride as positive control. The testosterone level was increased, indicating inhibition of 5α-reductase converting testosterone to dihydrotestosterone. This was confirmed by prostate-specific antigen level that significantly decreased when treated with PM extract, daidzein and genistein. The PM extract, daidzein and genistein reduced the increase in the prostate/body weight ratio in testosterone-induced rats. This gives indication that PM extract, daidzein and genistein possessed protective activity for the treatment of benign prostatic hyperplasia. The analysis of histoarchitechture of the prostate has also shown that there was a significant improvement in prostatic cells of the testosterone-induced rats when treated with PM extract, daidzein and genistein.

Viewpoint animation with a dynamic tether for supporting navigation in a virtual environment. This study examined the concept of dynamic viewpoint tethering for enhancing performance in 3-D avatar control tasks. Dynamic viewpoint tethering refers to a viewpoint animation technique that couples a display viewpoint to a controlled avatar through a virtual tether. A dynamic tether, modeled as a mass spring damper system, can potentially generate desirable viewpoint behavior because of its ability to produce frequency-separated viewpoint responses. This study investigated the impact of a tether's rigidity and damping properties on users' navigational performance. Twelve participants took part in a simulated 3-D aerial navigational task. Performance was evaluated with respect to local guidance and global awareness. Root mean square error scores revealed a decrease in local guidance performance when (a) the tether was either severely underdamped or overdamped and (b) the tether's rigidity approached either zero or infinity. In addition, (c) global performance was better for higher-frequency forcing functions. Critical damping and medium rigidity can be optimized during design for enhancing users' navigational efficiency. Guidelines generated from this study support future viewpoint design in interactive virtual reality applications.

Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response. Given the limitation of available antiviral drugs and vaccines, there remains to be a pressing need for novel anti-influenza drugs. Rupestonic acid derivatives were reported to have an anti-influenza virus activity, but their mechanism remains to be elucidated. Herein, we aim to evaluate the antiviral activity of YZH-106, a rupestonic acid derivative, against a broad-spectrum of influenza viruses and to dissect its antiviral mechanisms. Our results demonstrated that YZH-106 exhibited a broad-spectrum antiviral activity against influenza viruses, including drug-resistant strains in vitro. Furthermore, YZH-106 provided partial protection of the mice to Influenza A virus (IAV) infection, as judged by decreased viral load in lungs, improved lung pathology, reduced body weight loss and partial survival benefits. Mechanistically, YZH-106 induced p38 MAPK and ERK1/2 phosphorylation, which led to the activation of erythroid 2-related factor 2 (Nrf2) that up-regulated heme oxygenase-1 (HO-1) expression in addition to other genes. HO-1 inhibited IAV replication by activation of type I IFN expression and subsequent induction of IFN-stimulated genes (ISGs), possibly in a HO-1 enzymatic activity-independent manner. These results suggest that YZH-106 inhibits IAV by up-regulating HO-1-mediated IFN response. HO-1 is thus a promising host target for antiviral therapeutics against influenza and other viral infectious diseases.

The anatomic compression arthrodesis technique with anterior plate augmentation for ankle arthrodesis. The anatomic compression arthrodesis technique with anterior plate augmentation is an effective technique that results in a high union rate, improved functional outcome, and an acceptable complication rate. This technique can be used for both primary ankle arthrodesis and salvage cases with significant bone loss. The authors believe the anterior plate is a useful complement to standard multiplanar screw fixation, and the increased rigidity provided by the anterior plate effectively counters forces, particularly in the sagittal plane, that may otherwise lead to failure of multiplanar screw constructs.

Displacement of the bidentate malonate ligand from (d,l-trans-1,2-diaminocyclohexane)malonatoplatinum(II) by physiologically important compounds in vitro. Previous studies of platinum(II) compounds with bidentate leaving ligands have emphasized the contrast between the stability of the bidentate leaving ligand in vitro (T1/2 greater than 11 days in water) and the apparent reactivity of these bidentate platinum compounds in vivo. However, none of these studies actually measured the stability of these compounds in tissue culture medium (or in any other reaction mixture resembling in vivo conditions). The experiments described in this paper were designed to measure the stability and fate of (d,l-trans-1,2-diaminocyclohexane)malonatoplatinum(II) [Pt(mal)(trans-dach)] in RPMI-1640 tissue culture medium. The T1/2 for displacement of the malonate ligand in this medium was 9.5 hr at 37 degrees. Of the inorganic anions present in the medium, chloride accounted for the greatest displacement of the malonate ligand. However, at the concentrations with which it is found in tissue culture medium and in blood, bicarbonate was nearly as effective as chloride at displacing the malonate ligand. This observation is of particular significance because the bicarbonatoplatinum complex is unstable and the bicarbonate displacement reaction appears to represent a major non-enzymatic pathway for the formation of the biologically active aquated platinum complexes. At the concentrations with which they occur inside the cell, phosphates may play a similar role. Of the amino acids present in the medium, glutathione and the sulfur-containing amino acids were 50- to 400-fold more effective at displacing the malonate ligand than the other amino acids in RPMI-1640 medium. In the case of methionine, the reaction with Pt(mal)(trans-dach) was shown to be a direct displacement (SN2) reaction at physiological methionine concentrations. When Pt(mal)(trans-dach) was incubated at 37 degrees for 24 hr in RPMI-1640 medium, the major transformation products formed were (d,l-trans-1,2-diaminocyclohexane)methionineplatinum(II) (38%), other amino acid-platinum complexes (19%), and (d,l,-trans-1,2-diaminocyclohexane)dichloroplatinum(II) (14%). Eleven percent of the Pt(mal)(trans-dach) remained intact. Mass spectrometry and 1H-NMR indicated that the (d,l-trans-1,2-diaminocyclohexane)methionineplatinum(II) complexes that formed in RPMI-1640 medium consisted of approximately 60% of the bidentate mono-methionine complex coordinated to platinum at the sulfur and alpha-amino positions and 40% of the bis-methionine complex, presumably coordinated at the sulfurs.(ABSTRACT TRUNCATED AT 400 WORDS)

Vector ecology of equine piroplasmosis. Equine piroplasmosis is a disease of Equidae, including horses, donkeys, mules, and zebras, caused by either of two protozoan parasites, Theileria equi or Babesia caballi. These parasites are biologically transmitted between hosts via tick vectors, and although they have inherent differences they are categorized together because they cause similar pathology and have similar morphologies, life cycles, and vector relationships. To complete their life cycle, these parasites must undergo a complex series of developmental events, including sexual-stage development in their tick vectors. Consequently, ticks are the definitive hosts as well as vectors for these parasites, and the vector relationship is restricted to a few competent tick species. Because the vector relationship is critical to the epidemiology of these parasites, we highlight current knowledge of the vector ecology of these tick-borne equine pathogens, emphasizing tick transmissibility and potential control strategies to prevent their spread.

An intraatrial thrombus and pulmonary thromboembolism as a late complication of percutaneous vertebroplasty. Although percutaneous vertebroplasty is a simple and generally safe method for the management of vertebral compression fractures, cement leakage outside the vertebral body is a potential source of serious complications. We report a patient who presented with dyspnea and edema five years after percutaneous vertebroplasty and underwent open-heart surgery. This case demonstrates an intraatrial thrombus and pulmonary thromboembolism caused by venous leakage of polymethylmethacrylate as a late complication of the procedure.

The outermost capsular arabinomannans and other mannoconjugates of virulent and avirulent tubercle bacilli. It has been shown that phagocyte mannose receptors play an important role in phagocytosis of virulent tubercle bacilli, but not of avirulent strains. Accordingly, we investigated the occurrence and structure of the outermost mannoconjugates of the capsule of five strains of the tubercle bacillus differing in their degrees of virulence. The extracellular and surface-exposed arabinomannan-containing polysaccharides were chemically characterized as being composed mainly of neutral fatty-acyl-free arabinomannans (AMs) possessing a reducing end consisting of mannose. Although no lipoarabinomannan (LAM) was detected, small amounts of acidic polysaccharides, exhibiting the same electrophoretic mobility as LAM, were identified as succinylated AMs (two to three residues per molecule) lacking the phosphatidylinositol anchor of LAM. AMs from the different strains shared the same structural features, notably the capping of a large portion of the arabinan segments with mannosyl residues. However, no correlation was observed between either the percentage of capping or the amount of AMs and the degrees of virulence of the strains. The occurrence and amounts of other mannoconjugates (phosphatidylinositol mannosides and the mannose-associated 19 and 38 kDa lipoproteins) in the various tubercle bacilli were also examined. Although both classes of compounds were identified in all the examined strains, a correlation between the amounts of the glycoconjugates and the degrees of virulence of the strains could not be established. These data do not support the implication of these promising mannosylated molecules in the selective phagocytosis of virulent tubercle bacilli and indicate that the involvement of mannose receptors in phagocytosis of virulent M. tuberculosis needs to be re-investigated.

Genetic variants in the LPL and GPIHBP1 genes, in patients with severe hypertriglyceridaemia, detected with high resolution melting analysis. Pathogenic variants in lipoprotein lipase (LPL) and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) have been described in patients with severe hypertriglyceridaemia. We aimed to optimise high resolution melting (HRM) assays to detect the presence of functional variants in these genes. One hundred and sixteen patients with severe hypertriglyceridaemia were studied. HRM assays were optimised to scan exons and splice junctions in LPL and GPIHBP1. Sanger sequencing was the reference method. Next-generation-sequencing (NGS) was performed in five patients, including one with Familial Chylomicronemia syndrome (FCS). We identified 15 different variants in LPL and 6 in GPIHBP1. The variants revealed with NGS were also detected with HRM, including a rare premature stop codon in LPL (p.Trp421*) and two LPL pathogenic variants in the patient with FCS (p.His80Arg + p.Gly215Glu). Having multiple functional variant alleles was associated with pancreatitis onset at younger ages and higher baseline triglycerides. Our HRM assays detected the presence of functional gene variants that were confirmed with Sanger and NGS sequencing. The presence of multiple functional variant alleles was associated with differences in the clinical profile. Therefore, these assays represent a reliable, cost-effective tool that can be used to complement the NGS approach for gene scanning.

Solitary waves in a single-mode fiber with two-photon absorption and bandwidth-limited optical gain. The exact soliton solutions of the nonlinear Schrödinger equation and the extended nonlinear Schrödinger equation with two-photon absorption and bandwidth-limited optical gain, respectively, are given. The results show that both picosecond and femtosecond soliton pulses can be propagated in a single-mode fiber with twophoton absorption and symmetric optical gain with the proper spectral profile.

[Characteristics of RNA isolated from the nuclear RNA-synthesizing complex of influenza virus]. When Ehrlich ascitic carcinoma cells infected with classical fowl plague virus and treated with actinomycin D were pulse labeled for 10 min with 3H-uridine, it was mainly incorporated into nucleoplasm structures sedimenting in sucrose gradients at 120S. At 2-hr exposure of the infected cells to 3H-uridine radioactivity was found in nucleoplasm in the area of 65S and in the cytoplasm in 30-40S zone. The analysis of RNA isolated from these structures gave the following results. The RNA isolated from 120S structures sedimented in two zones of sucrose gradient: 11S and 16-23S. The 11S RNA was resistant to RNA-ase, while 16-23S RNA was sensitive to RNA-ase. A similar (16-23S) RNA was isolated from virus-specific structures 65S and 30-40S.

Lack of benefit of intravenous immune globulin in a murine model of group A streptococcal necrotizing fasciitis. Penicillin, clindamycin, and intravenous immune globulin (Venoglobulin-S; IVIG) alone and in combination were studied in a murine model of group A streptococcal necrotizing fasciitis. As assessed by bacterial clearance, treatment with IVIG was not significantly different from no treatment. All treatment regimens that contained penicillin or clindamycin were more effective (P<.05) than no treatment or treatment with IVIG alone. No significant differences were detected among results of treatment with penicillin, penicillin/clindamycin, penicillin/IVIG, clindamycin/IVIG, or all agents combined. Clindamycin alone was less effective than penicillin/IVIG (P=.02), penicillin/clindamycin (P=.009), clindamycin/IVIG (P=.04), or all agents combined (P=.02). No antagonism was observed with the addition of clindamycin or IVIG to penicillin.

Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study. The incidence of chemotherapy-induced amenorrhea (CIA) and the time to subsequent menstrual bleeding in premenopausal breast cancer patients treated with current standard chemotherapy regimens was examined. Four hundred sixty-six women ages 20 to 45 years at the time of diagnosis of a stage I to III breast cancer were recruited between January 1998 and July 2002. Patients completed monthly bleeding calendars from the time of study recruitment. Updated medical history data were obtained at 6-month intervals. Most women received doxorubicin and cyclophosphamide (AC); doxorubicin, cyclophosphamide, and paclitaxel (ACT); or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Approximately 41% of women experienced an initial 6 months of CIA, and an additional 29% had at least 1 year of CIA. Approximately half of the women with 6 months of CIA and 29% of those with 1 year of CIA resumed bleeding within the subsequent 3 years, usually in the year after their amenorrheic episode. Resumption of bleeding differed significantly by treatment regimen after 6 months of CIA (P = .002; 68% with AC, 57% with ACT, and 23% with CMF), but not after 1 year of CIA (P = .5). Of the 23% of women who experienced an initial 2-year period of CIA, 10% resumed bleeding within the ensuing 3 years after their amenorrheic episode, but none had regular menses. A considerable proportion of women treated with chemotherapy will experience periods of CIA, but many will resume bleeding. Newer treatment regimens such as ACT appear to have a higher resumption of bleeding compared with CMF. This finding may have implications for choice of anti-estrogen treatment and for future potential pregnancies/fertility.

Antimicrobial activity of extractives of Sarcocephalus coadunatus. The methanolic extracts and the fractions (petrol, dichloromethane, ethyl acetate, butanol) obtained from the leaves, seeds, stem and root barks of Sarcocephalus coadunatus exhibited a high level of broad spectrum antibacterial activity. The activity was more pronounced in the dichloromethane, ethyl acetate and butanol fractions of the leaves; ethyl acetate and butanol fractions of the seeds; dichloromethane fractions of the stem bark and the ethyl acetate fractions of the root bark. None of the fractions showed any antifungal activity.

Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup. The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning.

Identification of strain-specific nucleotide sequences in the RA 27/3 rubella virus vaccine. A polymerase chain reaction-based protocol was developed for determination of the sequence of 1300 nucleotides in the E1 coding region of the genomes of multiple strains of rubella virus. From a collection of sequences of 9 independent strains and isolates, characteristic nucleotides were identified that distinguished the RA 27/3 strain, which is the currently used attenuated vaccine strain. These characteristic nucleotides were maintained in virus recovered from recent vaccinees. Both the assay and the knowledge of these characteristic nucleotides should be of use in determining the origin of virus isolated from individuals who have suspected vaccine-associated complications. The nucleotide sequences of the independent rubella virus strains differed by 0.7%-3.6%. Phylogenetic tree analysis of the sequences indicated the existence of at least three distinct genetic lineages.

Ozone inhalation effects consequent to continuous exercise in females: comparison to males. Exposure to ozone (O3) at ambient photochemical smog alert levels has been shown to cause alteration in pulmonary function and exercise response in humans, but there is a paucity of data on females. The initial purpose of the present investigation was to study the effects of O3 inhalation on pulmonary function and selected exercise respiratory metabolism and breathing pattern responses in young adult females. Six female subjects exercised continuously on a bicycle ergometer for 1 h on 10 occasions at one of three intensities, while exposed to 0.0, 0.20, 0.30, or 0.40 ppm O3. Forced expiratory volume and flow rates and residual volume (RV) were measured before and immediately following each protocol. During exercise, expired minute ventilation (VE), respiratory frequency (fR), tidal volume, O2 uptake (VO2), and heart rate (HR) were measured every 10 min. O3 dose-dependent decrements were observed for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow rate during the middle half of FVC, coupled with an increase in RV and altered exercise ventilatory pattern. There was also an increased VE but no significant O3 effect on VO2 or HR. Comparison of the females' responses to those of a group of young adult males (previously studied) at the same total O3 effective dose (i.e., expressed as the simple product of O3 concentration, VE, and exposure time) revealed significantly greater effects on FVC, FEV1.0, and fR for the females. With VE reduced for females as a function of exercise intensity at the same percent of maximum VO2, these differences were considerably attenuated, although not negated.(ABSTRACT TRUNCATED AT 250 WORDS)

Merkel Cell Carcinoma in a Steer. Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine tumour reported only in man, dogs and cats. A 20-month-old Japanese black fattening steer was presented with necrotic protruding skin masses over the left thoracic area and a 20 × 25 cm subcutaneous mass in the left abdominal area. Microscopical evaluation of the masses revealed cords of small to medium-sized round tumour cells with marked anisocytosis and anisokaryosis and clear and vacuolated cytoplasm, which were separated by a delicate fibrovascular stroma and arranged in a trabecular and nested pattern. Necropsy examination revealed multiple solid white nodular masses in the lungs. Immunohistochemistry (IHC) for cytokeratin (CK) 20 and CKAE1/3 revealed focal perinuclear labelling of tumour cells. IHC for the neuroendocrine markers chromogranin A and neuron specific enolase, the neuroepithelial stem cell marker nestin and the hormonal markers adrenocorticotropic hormone and calcitonin revealed diffuse cytoplasmic labelling of all tumour cells. Ultrastructurally, the tumour cells contained few neurosecretory granules and abundant glycogen pools. The tumours were diagnosed as Merkel cell carcinoma with pulmonary metastases and this case represents the first such diagnosis in cattle.

[Evaluation of topical calcipotriol in psoriasis]. Calcipotriol is an analogue of vitamin D3 with effect on epidermal keratinization, cellular division and modulation of immune response. An evaluation of its therapeutic effect when given in twenty-five psoriatic patient with less than 25% of their body surface affected was done. The medication was applied twice daily during six weeks on involved areas. The evolution was evaluated by the psoriatic area and severity index (PASI) analysis. The evaluation of initial and terminal PASI analysis revealed a decrease in the psoriatic activity that fluctuated from 25% to 100%, with a 61% average. A reactivation in the psoriatic lesion was noticed two weeks after the medication was halted; thereafter, the calcipotriol was restarted for an additional four weeks and a decrease in their PASI with a 74% average was achieved. There were no important side effects reported. Calcipotriol is effective in the treatment of psoriasis and it is an important addition to the therapeutic medications available to treat psoriasis. It is important to give the treatment for longer periods of time for evaluating the possibility to induce prolonged remissions.

Decoupling of QT interval variability from heart rate variability with ageing. Ageing has been associated with changes in cardiac electrophysiology that result in QT interval prolongation. The effect of age on rate-adaptation dynamics of the QT interval is less well understood. The aim of this study was to assess age-related changes in the temporal relationship between QT and RR interval variability. Resting ECG of 20 young and 20 elderly healthy subjects were analyzed. Beat-to-beat RR and QT interval time series were automatically extracted. Coupling between QT and RR was assessed by means of the QT variability index, coherence in the frequency domain, rate-corrected QT interval, cross-multiscale entropy, information based similarity index and joint symbolic dynamics. In addition to QT interval prolongation (433 ± 31 versus 405 ± 33 ms, p = 0.008), elderly subjects were characterized by a significantly increased QT variability index (-1.26 ± 0.28 versus -1.52 ± 0.22 ms, p < 0.0001), reduced coherence in high (0.11 ± 0.09 versus 0.29 ± 0.14 ms, p = 0.003), and low frequency bands (0.20 ± 0.16 versus 0.49 ± 0.15 ms, p < 0.0001), reduced information domain synchronization index (0.13 ± 0.07 versus 0.19 ± 0.05 ms, p = 0.001) as well as increased entropy and disparity in joint symbolic dynamics of QT and RR interval time series. In conclusion, ageing is associated with decoupling of QT variability from heart rate variability. Complexity analysis in addition to standard metrics may provide additional insight.

IBS-catalyzed oxidative rearrangement of tertiary allylic alcohols to enones with oxone. A 2-iodoxybenzenesulfonic acid (IBS)-catalyzed oxidative rearrangement of tertiary allylic alcohols to enones with powdered Oxone in the presence of potassium carbonate and tetrabutylammonium hydrogen sulfate has been developed.

The Suicide Prevention, Depression Awareness, and Clinical Engagement Program for Faculty and Residents at the University of California, Davis Health System. The authors replicated a program developed by UC San Diego, identified medical staff at risk for depression and suicide using a confidential online survey, and studied aspects of that program for 1 year. The authors used a 35-item, online assessment of stress and depression depression developed and licensed by the American Foundation for Suicide Prevention that aims to identify and suicide risk and facilitate access to mental health services. During 2013/2014, all 1864 UC Davis residents/fellows and faculty physicians received an invitation to take the survey and 158 responded (8% response rate). Most respondents were classified at either moderate (86 [59%]) or high risk for depression or suicide (54 [37%]). Seventeen individuals (11%) were referred for further evaluation or mental health treatment. Ten respondents consented to participate in the follow-up portion of the program. Five of the six who completed follow-up surveys reported symptom improvement and indicated the program should continue. This program has led to continued funding and a plan to repeat the Wellness Survey annually. Medical staff will be regularly reminded of its existence through educational interventions, as the institutional and professional culture gradually changes to promptly recognize and seek help for physicians' psychological distress.

Medical, epidemiologic, and social aspects of aging urinary incontinence questionnaire: Study protocol for the translation and validation of a Chinese language version. Mixed urinary incontinence (MUI) is a coexistence of both urgency urinary incontinence and stress urinary incontinence. Medical, Epidemiologic, and Social aspects of Aging (MESA) questionnaire is a validated and commonly used tool to diagnose predominant components of it and assess the severity, which can offer help in clinic. However, MESA questionnaire is still not available in China. The aim of the study is to translate English MESA questionnaire into a Chinese version, adapt it in Chinese culture, and validate the measurement properties among female patients with MUI and urgency-predominant MUI. MESA questionnaire will be translated and culturally adapted in China. The validation will be embedded in a multicentered randomized controlled trial targeted at women with urgency-predominant MUI. Apart from MESA questionnaire, 3 groups of patients are to receive clinical extended assessment, keep 3-day voiding diary, and complete International Consultation on Incontinence Questionnaire Short Form to evaluate the measurement properties of reliability and validity (internal consistence, test-retest reliability, construct validity, and responsiveness). If MESA questionnaire is of relatively high reliability and validity in diagnosing subtypes of MUI and assessing the severity, it can help to choose more appropriate therapy for patients and simplify the workload of clinicians. ClinicalTrials.gov NCT03803878, January 11, 2019.

Selection of a representative set of chemical accidents from a complex data matrix for the development of environment-accident index. Chemical accidents often lead to negative consequences for the environment. Preparedness and proper actions are, therefore, essential components in order to minimise environmental effects. To assist and facilitate this work, a proposed planning tool, the environment-accident index (EAI), was formulated by Scott [J. Hazard. Mater. 61 (1998) 305]. As a result of a first validation of the index, based on 21 chemical accidents, the database was complemented with 42 additional accidents covering a broader spectrum of chemicals. The additional accidents were collected by means of an inquiry and their environmental consequences are, so far, unknown. The collected data had an overrepresentation of accidents involving petroleum products (69%). Because of the overrepresentation of this group of chemicals in the material, the data was skewed with respect to chemical properties. Since the model should be valid for a variety of chemical accidents, a method was needed which enabled a proper and unbiased selection of a representative subset of accidents to be used in development and validation of the model. For this purpose, the possibility to use multivariate data analysis in combination with statistical design was investigated. The result showed the feasibility of this method in the selection of a representative subset from a complex and skewed large dataset. Within the new dataset, 53% were accidents involving petroleum products and 47% involved other chemicals. The selected accidents will be used in further work to evaluate the environmental consequences, for model development and model validation.

Factors predicting choice of provider among homeless veterans with mental illness. Homeless persons with serious mental illness are especially likely to lack access to comprehensive medical and psychiatric care. This study examined the relative importance of predisposing factors, illness factors, and enabling factors as determinants of the use of Veterans Affairs (VA) health care services by mentally ill homeless veterans seeking services from a non-VA program. Predisposing factors included demographic characteristics and wartime service; illness factors were related to the type of medical problem and the need to seek medical care; and enabling factors included entitlement to VA medical services and location of VA facilities. Logistic regression analysis was used to analyze data for 698 homeless veterans with mental illness who were enrolled in the Access to Community Care and Effective Services and Supports (ACCESS) program. About 56 percent of the mentally ill homeless veterans had used VA services at some time in their lives. Homeless veterans were almost twice as likely as other poor veterans to use VA services; those with a dual diagnosis were also more likely to use VA services. Enabling factors were more important than either predisposing or illness factors in predicting VA service use. Veterans most likely to use VA services were those who received VA benefits that gave them priority access to VA services and those who lived near a VA medical center. Specific characteristics of the service system and of veterans' entitlement were more important than clinical needs or predisposing factors in predicting service use.

Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial. Only limited data are available on the effectiveness of augmented antipsychotics to clozapine therapy in chronic schizophrenia. We conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of augmentation with the atypical neuroleptic amisulpride to clozapine in a small sample group of patients. 16 patients with the DSM-IV diagnosis of chronic schizophrenia and partially responsive to clozapine participated in this pilot study. Patients on a steady dose of clozapine randomly received either clozapine and amisulpride 400 mg/day (n=7) or clozapine and amisulpride 600 mg/day (n=6) or clozapine and placebo for 6 weeks (n=3). Efficacy measures were BPRS, CGI, GAF and MADRS score. Side effects and prolactin levels were obtained. Primary outcome measure were BPRS score changes. The beneficial effect of augmented amisulpride at a daily dose of 600 mg was observed in the mean scores of secondary outcome measures, as assessed by GAF, CGI and MADRS. Measures of primary objectives failed to improve significantly. No reduction in BPRS total score was achieved due to lack of power of the study, whereas the BPRS subscore "activity" had a tendency to improve. Amisulpride was more beneficial in a higher than a lower dose. No severe side-effects occurred, but tremor, bradykinesia, akathisia and elevated prolactin levels were recorded. Augmented amisulpride improved the global outcome of patients suffering from chronic schizophrenia in this pilot study and tended to be a helpful treatment option in cases of partial or non-responsiveness to clozapine. Limitations emerge from the small sample size and lack of power. Further investigation requires a larger number of patients to be included.

[Doppler sonography assessment of blood flow velocity in the ascending aorta. Problems and possible solutions]. Irregularities of the transvascular distribution of blood flow within the human ascending aorta have been documented by means of 16 Doppler gates positioned along one scanline of a sector scanner. The velocity profiles recorded from ten healthy adults, ten patients suffering from hypertrophic obstructive cardiomyopathy, ten patients suffering from hypertrophic nonobstructive cardiomyopathy, and ten patients with severe aortic insufficiency exhibited nonuniformities which varied not only from individual to individual but also between the groups and depending on the phase of the cardiac cycle. These variations prevent any local measurement from being representative for the instantaneous mean velocity in all cases. A reliable mean should therefore be determined by simultaneously taking into account all velocities within the vascular cross-section. A computer simulation in order to indicate a potential solution to this problem demonstrates that an annular array transducer can be excited in such a manner that it produces a homogeneous ultrasound beam of a transverse area a hundred times larger than the one obtained in the conventional maximally focussed mode.

Immunocytochemistry of the C-terminal peptide of propressophysin (CPP): relationship to vasopressin, oxytocin and neurophysin. Arginine-vasopressin (AVP) and its associated neurophysin (AVP-NP) are synthesized via a precursor, propressophysin, which also contains a 39 amino acid glycopeptide at its C-terminus (C-terminus of propressophysin, or CPP). In the present study, immunocytochemical techniques were used to determine the cellular co-localization of CPP with AVP, oxytocin (OXY), AVP-NP and OXY-NP in the rat hypothalamus using colchicine pre-treatment and serial 5 micron section analysis. Extensive cross-competition studies of antisera raised against each peptide with the various antigens yielded no significant crossreactivity of the CPP, AVP, OXY and NP antisera. The NP antiserum, although directed against both AVP-NP and OXY-NP, demonstrated a preference for OXY-NP at a dilution of 1:20,000. CPP and AVP were always co-localized within the same magnocellular neurons of the supraoptic, paraventricular and circularis nuclei, and further showed very similar patterning in the suprachiasmatic nucleus as well. In contrast, no cellular overlap could be detected between CPP and OXY, in any of the above nuclei (the suprachiasmatic nucleus is devoid of OXY). Likewise, no examples of co-localization of CPP and OXY-NP were found in the magnocellular nuclei. These results are in strong agreement with a biosynthetic relationship between CPP, AVP and AVP-NP, and their separateness from the OXY and OXY-NP precursor.

Characterisation of early and late bovine papillomavirus protein expression in equine sarcoids. Sarcoids are common skin tumours of horses and donkeys that are characterised by persistent proliferation of dermal fibroblasts associated with the presence of bovine papillomavirus (BPV) DNA. Some early BPV proteins have been demonstrated within sarcoids and RNA containing both early and late transcripts is present, yet it remains unclear whether late replication of BPV, culminating in the production of infectious virus particles, can occur in equids. Here we report that BPV1 RNA isolated from equine sarcoids encodes a unique deletion of four residues within the L2 protein suggesting a novel variant of virus has evolved in equines. Such viral evolution would require the production and transmission of virus particles among horses with sarcoids. Quantitative RT-PCR demonstrated the presence of mRNA transcripts containing early gene message in sarcoid tissues and BPV-E2 early virus antigen was detected by immunofluorescence in the nuclei of dermal fibroblasts, but no E2 expression could be detected within the overlying epidermis where productive virus replication would be expected to occur. Although immunohistochemistry clearly detected late virus proteins in the nuclei of dermal cells from samples of bovine papillomas, no late protein expression was detected in formalin-fixed tissue from equine sarcoids; either in the dermis or epidermis. Moreover, quantitative RT-PCR demonstrated that late gene mRNA represented <0.3% of the transcribed BPV RNA. We conclude that BPV does not undergo productive infection in the epidermis overlying equine sarcoids at levels comparable with that occurring in its natural bovine host.

Brain stem auditory evoked responses: studies of waveform variations in 50 normal human subjects. Brain stem auditory evoked responses (BAERs) were recorded in 50 normal adult subjects at various click rates. Attention was paid to absolute latencies, interwave latencies, interear interwave latencies, absolute amplitudes, and various amplitude ratios. The variability of waves VI and VII suggests that the clinical utility of these waves is restricted-their absence is not necessarily due to a CNS lesion. The wave IV-V complex appears with six different patterns. These variations must therefore be considered normal; none should be misconstrued as indicative of disease of the CNS. Repeated studies over a period of two to nine months showed no statistically significant changes in amplitude or latency measurements with the passage of time. Knowledge of these normal values and their variations, as a precondition for establishing criteria for abnormality, is essential to the interpretation of BAERs in clinical situations.

Cyclosporine A decreases kallikrein and BK2 mRNA expression in the rat renal cortex. The effect of subcutaneous injection of cyclosporine (20 mg/kg/day for 3 days) on the expression of kallikrein (Kal) and bradykinin 2 receptor (BK2) mRNA in the rat renal cortex was examined. CsA decreased significantly Kal and BK2 mRNA expression in the kidney cortex. These results indicate that the kallikrein-kinin system may participate in the genesis or the aggravation of the renal haemodynamic effect induced by long term administration of CsA.

Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: focusing on an effect of the number of mediastinal lymph node stations involved. Postoperative radiotherapy (PORT), especially using modern technology, for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We retrospectively investigated 112 patients with stage IIIA-N2 NSCLC who underwent complete resection of the lung tumor in our institution from 1986 through 2003. Among the 91 patients determined suitable candidates for PORT postoperatively, 45 patients received PORT (PORT group) and 46 did not (non-PORT group). We analyzed the correlation between PORT use and clinicopathological characteristics, number of involved mediastinal lymph node stations, recurrence, and survival. Five-year and 10-year survival rates of PORT group were 53.2% and 40.0%, which were superior, however, not statistically different, to those (39.3% and 27.5%) of non-PORT group (P=0.6284). According to the number of mediastinal lymph node stations, PORT was more effective for multiple station metastasis than single station metastasis. The disease-free survival of PORT group was significantly better than that of non-PORT group among the patients with multiple station metastasis. Five-year disease-free survival rate of PORT group and non-PORT group were 41% and 5.9%, respectively (P=0.0220). PORT using modern techniques can reduce local recurrence and improve overall survival especially for patients with multiple station N2. Prospective randomized control trials are warranted.

Laparoscopic versus open myomectomy: a double-blind study to evaluate postoperative pain. The advantages of laparoscopic over open surgery have been documented in nonblinded settings. Our prospective, double-blind setting evaluated pain scores 72 h after surgery by comparing patients who underwent laparoscopic myomectomy or with laparotomy. Forty women referred for conservative myomectomy were included in the study. After stratification (myoma size, number of myomas, and surgeon), patients were randomized to either laparoscopy (n = 19) or laparotomy (n = 21) and received a standardized anesthesia and patient-controlled analgesia for 24 h after surgery. Identical wound dressings were applied to blind the patient and the observer to the surgical approach. The postoperative pain scores were documented on a visual analog scale (VAS; 0 = no and 10 = unbearable pain) at 24, 48, and 72 h after surgery. As the primary outcome variable, we calculated the mean overall VAS-score at these time points. P < 0.05 (t-test and analysis of covariance) was considered statistically significant. There were no differences in patient characteristics among the groups. The mean overall VAS score at 24, 48, and 72 h was statistically significantly lower in the laparoscopic group compared with the laparotomy group (2.28 +/- 1.38 versus 4.03 +/- 1.63; P < 0.01). Our data demonstrate, for the first time in a double-blind setting, that laparoscopic myomectomy reduces postoperative pain for 72 h after surgery compared with laparotomy.

Molecular cloning and tissue-specific expression of mouse kidney 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. A 1932 bp cDNA clone encoding a novel isozyme of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (PFK-2/ FBPase-2) was isolated from a mouse kidney cDNA library. The sequence encodes 519 amino acids and, based on homology to rat heart genomic sequence, appears to be the product of alternative splicing from PFK-2/FBPase-2 gene B with an extended version of exon 15. Northern blot analysis indicated that this clone corresponds to an 8 kb mRNA expressed in multiple tissues, with the strongest signal in kidney, and detects several additional transcripts which may be alternatively spliced from gene B.

Calycosin and genistein induce apoptosis by inactivation of HOTAIR/p-Akt signaling pathway in human breast cancer MCF-7 cells. Calycosin and genistein are the two main components of isoflavones. Previously, we reported that these compounds display antitumor activities in the breast cancer cell lines MCF-7 and T47D. In the present study, we investigated the mechanism of action of calycosin and genistein, and their respective efficacies as potential therapies for the treatment of breast carcinoma in the clinic. MCF-7 cells were treated with calycosin or genistein. Cell proliferation and apoptosis were measured using CCK8 assay and Hoechst 33258. The expression level of phosphorylated Akt protein was determined by western blotting. Expression level of HOTAIR was quantified by real-time PCR. Both calycosin and genistein inhibited proliferation and induced apoptosis in MCF-7 breast cancer cells, especially after treatment with calycosin. Treatment of MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of Akt, and decreased expression of its downstream target, HOTAIR. Calycosin is more effective in inhibiting breast cancer growth in comparison with genistein, through its regulation of Akt signaling pathways and HOTAIR expression.

Survival and Progression in Synucleinopathy Phenotypes With Parkinsonism: A Population-Based Study. To compare survival by the presenting parkinsonism symptoms at diagnosis among patients with incident clinically diagnosed synucleinopathies. Using the Rochester Epidemiology Project medical records-linkage system, we identified all persons residing in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from January 1, 1991, through December 31, 2010. A movement disorder specialist reviewed the complete medical records of each individual to confirm the presence of parkinsonism, determine the type of synucleinopathy, and identify the onset dates of each cardinal symptom (tremor at rest, bradykinesia, rigidity, and impaired postural reflexes). We determined the median time from age at diagnosis to death or censoring (June 30, 2015) for each presenting symptom and the age- and sex-adjusted risk of death. From 1991 through 2010, a total of 433 individuals had a synucleinopathy diagnosed (301 [69.5%], Parkinson disease; 68 [15.7%], dementia with Lewy bodies; 52 [12.0%], Parkinson disease dementia; and 12 [2.8%], multiple systems atrophy with parkinsonism). Overall, the risk of death in the tremor-predominant group was less than that in the bradykinesia/rigidity-only group (hazard ratio [HR], 0.59; 95% CI, 0.40-0.87; P=.007). Similarly, risk of death in the bradykinesia/rigidity-only group was significantly greater than in the tremor-predominant group (HR, 1.75; 95% CI, 1.23-2.51; P=.002) and compared with tremor before bradykinesia (HR, 1.75; 95% CI, 1.24-2.47; P=.001). Patients with tremor as a presenting symptom have longer survival. In contrast, the presence of bradykinesia/rigidity as a presenting symptom correlates with reduced survival across all types of synucleinopathies.

Randomized controlled trials. Proponents of evidence-based medicine would acknowledge that several sources of evidence inform clinical decision making. Hierarchies of evidence have, however, been developed to help describe the quality of evidence that may be found to answer our clinical questions. According to this classification, the randomized clinical trial is the most effective way to determine whether a cause-and-effect relationship exists between an intervention and a predefined outcome. The basic principles of clinical trial design are reviewed, and the unique challenges of trial design in surgery are discussed.

Do looks matter? The role of the Electronic Residency Application Service photograph in dermatology residency selection. There is a lack of research on the impact of the Electronic Residency Application Service (ERAS) photograph on the residency selection process. We sought to elucidate the role of the ERAS photograph in the dermatology residency selection outcome and to determine if photographs submitted by matched applicants differ from those of unmatched applicants. We analyzed ERAS photographs submitted by dermatology residency applicants based on photograph characteristics related to composition, attire, facial expression, hairstyle, and accessories. Candidates who smiled, wore glasses, and wore jackets in their photographs were more likely to match. There was no difference in the rate of matching among applicants depending on whether their photograph was of professional quality or whether they wore formal attire in their pictures. Gender specific characteristics were not found to be influential in the match outcome for male applicants. Among female applicants, having hair to the shoulders or longer was associated with a positive match outcome. Certain characteristics of the ERAS photographs were found to be associated with a more favorable match outcome. Further biases inferred from these photographs might be present in the dermatology selection process. We suggest blinding the selection committees to ERAS application photographs prior to granting residency interviews.

Near infra-red emission from a mer-Ru(II) complex: consequences of strong σ-donation from a neutral, flexible ligand with dual binding modes. A rare example of dual coordination modes by a novel tridentate ligand gives rise to unique fac-and mer-Ru((II/III)) complexes. The mer-Ru(II)-complex displays the farthest red-shift of a triplet metal-to-ligand charge transfer ((3)MLCT) emission with a tridentate ligand for a mononuclear complex. This observation is a consequence of large bite angle and strong σ-donation by the ligand, the combined effect of which helps to separate the energy of the (3)MLCT and (3)MC states.

A duty to participate in research: does social context matter? Because of the important benefits that biomedical research offers to humans, some have argued that people have a general moral obligation to participate in research. Although the defense of such a putative moral duty has raised controversy, few scholars, on either side of the debate, have attended to the social context in which research takes place and where such an obligation will be discharged. By reflecting on the social context in which a presumed duty to participate in research will obtain, this article shows that decontextualized discussions of this putative moral obligation are problematic.

Thromboelastograph assay for measuring the mechanical strength of fibrin sealant clots. In order to provide sustained hemostasis or tissue sealing, fibrin sealants must generate adhesive clots with mechanical properties capable of resisting forces, such as shear, that might break or tear the clot. Commercial preparations of fibrin sealants should generate clots of adequate and consistent mechanical strength. The mechanical strength of fibrin sealants is often measured as bonding strength in in vivo or ex vivo animal wound models. These tests can be useful predictors of clinical efficacy. However, these, as well as many in vitro tensile strength tests for fibrin sealant, tend to be laboratory specific and require extensive reagent preparation time and analyst training. The thromboelastograph has historically been used to screen for plasma protein and platelet disorders that lead to defective clot formation. The authors have developed a simple in vitro test, using a standard thromboelastograph that can provide reliable, reproducible information on the rheology of clots generated by fibrin sealant preparations. Using this method, the shear strength of fibrin sealant clots was measured and shown to correlate with the fibrinogen, but not the thrombin, concentration in the sealant. Shear strength was also shown to correlate with the sealant concentration of the fibrin cross-linking proenzyme, factor XIII. Sealants containing lysine, which can act as an alternate substrate for factor XIII enzyme and prevent efficient fibrin chain cross-linking, were shown by this method to generate clots of substantially reduced shear strength. The method distinguished between thrombin-catalyzed clot formation and other fibrinogen clotting mechanisms as evidenced by the significantly lower shear strength associated with batroxobin-generated fibrin clots.

Inhibitory effects of hyperglycemia on neural activity of the vagus in rats. Although it has been demonstrated that hyperglycemia inhibits gastrointestinal (GI) motility, its inhibitory mechanism remains unclear. Electrophysiological study. As GI motility is under the influence of the vagus, we studied the effects of hyperglycemia on neural activity of the dorsal motor nucleus of vagi (DMV) in anesthetized rats. A tungsten electrode was placed in the left side of the DMV area and extracellular electrical signals from the electrode were recorded. Single unit nerve activity was identified by the discriminator. D-glucose infusion elevated the peripheral blood glucose concentration from 3.4-5.9 mm to 12.0-21.8 mm and the neural firing of the DMV was significantly reduced by D-glucose infusion. After the 30 min D-glucose infusion, saline was re-infused for 90 min. Blood glucose level returned to 6.5-7.8 m m and the neural firing partially recovered 90 min after the saline re-infusion. There was a significant negative correlation observed between the counts of neural spikes and blood glucose concentrations ( r=0.84, p<0.01). It is suggested that hyperglycemia impairs GI motility by inhibiting vagal efferent activity. A recent study in intensive care unit (ICU) patients demonstrated that uncontrolled hyperglycemia is associated with poor outcomes. We propose that glycemia control is crucial in ICU patients to maintain the GI motility and vagus nerve activity.

[Molecular biology of glycoconjugates in eukaryotic cells]. Glycoconjugates, such as glycoproteins and glycolipids, are one of the macromolecules composing a living body. Biological roles of carbohydrate moieties in glycoconjugates have recently drawn great attention. Sugar chains of glycoconjugates comprise an enormous diversity of structures which are known to be expressed in a cell specific manner and are regulated with stage specificity during embryogenesis and cell-differentiation. It is generally accepted that genetic expression and regulation of glycosyltransferases which are present in Golgi apparatus determines the structures of sugar chains. For these several years, a number of successes of cDNA cloning of glycosyltransferases have been reported. Recent progress and accumulated molecular cloning evidences of glycosyltransferases are reviewed and future advance using cloned genes as useful tools for glycobiology and glycotechnology is discussed.

GC content dependency of open reading frame prediction via stop codon frequencies. A frequently used approach for detecting potential coding regions is to search for stop codons. In the standard genetic code 3 out of 64 trinucleotides are stop codons. Hence, in random or non-coding DNA one can expect every 21st trinucleotide to have the same sequence as a stop codon. In contrast, the open reading frames (ORFs) of most protein-coding genes are considerably longer. Thus, the stop codon frequency in coding sequences deviates from the background frequency of the corresponding trinucleotides. This has been utilized for gene prediction, in particular, in detecting protein-coding ORFs. Traditional methods based on stop codon frequency are based on the assumption that the GC content is about 50%. However, many genomes show significant deviations from that value. With the presented method we can describe the effects of GC content on the selection of appropriate length thresholds of potentially coding ORFs. Conversely, for a given length threshold, we can calculate the probability of observing it in a random sequence. Thus, we can derive the maximum GC content for which ORF length is practicable as a feature for gene prediction methods and the resulting false positive rates. A rough estimate for an upper limit is a GC content of 80%. This estimate can be made more precise by including further parameters and by taking into account start codons as well. We demonstrate the feasibility of this method by applying it to the genomes of the bacteria Rickettsia prowazekii, Escherichia coli and Caulobacter crescentus, exemplifying the effect of GC content variations according to our predictions. We have adapted the method for predicting coding ORFs by stop codon frequency to the case of GC contents different from 50%. Usually, several methods for gene finding need to be combined. Thus, our results concern a specific part within a package of methods. Interestingly, for genomes with low GC content such as that of R. prowazekii, the presented method provides remarkably good results even when applied alone.

Follicle stimulating hormone stimulates the production of gonadotrophin surge attenuating factor (GnSAF) in vivo. To study the time-course production of gonadotrophin surge attenuating factor (GnSAF) after the onset of FSH treatment in women. Normally cycling women were treated with FSH injections (225 IU per day) starting on cycle day 2 (0800 h). The response of LH to an i.v. injection of 10 micrograms GnRH (GnSAF bioactivity) was investigated 12, 24, 36 and 48 hours after the first FSH injection, as well as during the early follicular phase of an untreated spontaneous cycle. Six normally ovulating women with long-standing unexplained infertility were studied. The women were used as their own controls during the spontaneous cycles. Pituitary response to GnRH was calculated as the net increase in LH at 30 min (delta LH30) above the basal value. delta LH30 was significantly attenuated 12, 24, 36 and 48 hours after the first FSH injection as compared to the spontaneous cycles. In the latter cycles, delta LH30 decreased significantly from day 2 (12 hours) to day 4 (48 hours). Serum oestradiol levels at 12 and 24 hours did not differ significantly between the FSH and the spontaneous cycles. These results demonstrate that in superovulated women, a marked attenuation in the pituitary response to GnRH occurs as early as 12 hours from a single injection of FSH before any significant increase in serum oestradiol levels. It is suggested that FSH is a potent stimulus of GnSAF production in women.

Psychometric properties of the CAHPS 1.0 survey measures. Consumer Assessment of Health Plans Study. Consumer surveys are being used increasingly to assess the quality of care provided by health plans, physician groups, and clinicians. The purpose of the Consumer Assessment of Health Plans Study (CAHPS) is to develop an integrated and standardized set of surveys designed to collect reliable and valid information about health plan performance from consumers. This article reports psychometric results for the CAHPS 1.0 survey items in samples of individuals with Medicaid or private health insurance coverage. Reliability estimates for CAHPS 1.0 measures were estimated in a sample of 5,878 persons on Medicaid and 11,393 persons with private health insurance. Correlations of the CAHPS global rating of the health plan with willingness to recommend the plan and intention to re-enroll were estimated in a sample of 313 persons on Medicaid. The association of the rating of the health plan with ratings using a 5-point Excellent-to-Poor response scale also was investigated in the latter sample and in a sample of 539 persons with private health insurance. The CAHPS measures appeared to have good reliability, particularly at the health-plan level. Responses from 300 consumers per health plan tend to yield estimates that are reliable enough for health plan comparisons, especially among the privately insured. The global health plan rating was significantly correlated with consumers' willingness to recommend the plan to family and friends and to their intention to re-enroll in the plan if given a choice. The CAHPS 1.0 survey instrument appears to have excellent psychometric properties.

Regulation of the biopotency of primate luteinizing hormone by gonadotropin-releasing hormone in vitro and in vivo. Gonadotropin biological/immunological (B/I) ratios have proven to be valuable indicators of the biopotencies of LH and FSH. Observations of rapidly changing LH B/I have been made which suggest the existence of a readily mobilized pool of highly bioactive pituitary gonadotropins. To test this hypothesis, we have examined the role of GnRH in the regulation of LH B/I in vivo and in vitro. The rhesus monkey was used as a model due to its many physiological similarities with the human. A rapid elevation in circulating LH B/I was observed following GnRH administration to male monkeys that was sustained for at least 2 h (15 min; p less than 0.05). The administration of 1 or 10 nM GnRH to cultured pituitary cells was found to significantly increase the B/I of secreted, but not intracellular, LH (p less than 0.05). In unstimulated controls, the B/I of intracellular LH was higher than that of secreted LH (p less than 0.05). These findings are consistent with the notion that a pool of highly active LH exists within the gonadotrophs in primates. One way that GnRH may regulate the bioactivity of circulating LH is by rapidly mobilizing this gonadotropin pool.

Anticoagulant properties in vitro of heparan sulphates. The anticoagulant properties in vitro of eight heparan sulphate preparations were studied using clotting (APTT, anti-Xa) and amidolytic (anti-Xa, anti-thrombin) assays. Activities ranged from very low levels (less than 5 iu/mg) up to values similar to those of heparin. Activities measured by APTT assay showed the best correlation with the sulphate to carboxylate ratio of the heparan sulphates. Highest activities were obtained in the anti-Xa clotting assay, these being approximately two-fold greater than activities in the anti-Xa amidolytic assay. Five of the heparan sulphate preparations were readily neutralised by protamine sulphate, whereas the three heparans with the lowest sulphate to carboxylate ratio were much more resistant to neutralisation. After fractionating each heparan sulphate into At III-binding and non-binding material, it was found that the anti-coagulant properties were associated only with the former. It is concluded that these properties are dependent on the activation of At III.

Quenching of the tyrosyl free radical of ribonucleotide reductase by nitric oxide. Relationship to cytostasis induced in tumor cells by cytotoxic macrophages. Nitric oxide (NO) synthesized by macrophages inhibits tumor cell replication. NO also inhibits ribonucleotide reductase, an enzyme essential for DNA synthesis, probably by quenching the catalytically active tyrosyl free radical of its R2 subunit. The role of this inhibition in NO-mediated cytostasis was thus evaluated. After a 4-h coculture with macrophages, quenching of the radical was demonstrated by electron paramagnetic resonance spectroscopy in transfected L1210-R2 cells over-expressing the R2 protein. Pronounced cytostasis was simultaneously observed. A NO synthase inhibitor greatly reduced both phenomena. Target cells withdrawn from macrophages partially recovered from cytostasis and radical loss within 90 min. Deoxyribonucleosides added to by-pass ribonucleotide reductase inhibition efficiently reversed cytostasis of K-562 cells. After a 24-h coculture, the quenched tyrosyl radical still reappeared in L1210-R2 cells withdrawn from macrophages, but DNA synthesis did not resume. Moreover, deoxyribonucleosides marginally reversed overnight cytostasis of K-562 cells mediated by macrophages but were efficient against cytostasis induced by hydroxyurea, a ribonucleotide reductase inhibitor. Autocrine cytostasis observed early in TA3-H2 cells committed to produce NO was closely correlated with quenching of the tyrosyl radical but not with formation of dinitrosyl-iron complexes. We thus propose that NO-dependent cytostasis begins with a rapid and reversible inhibition of ribonucleotide reductase, progressively reinforced by other, long-lasting antiproliferative effects.

Effects of orexins on the hypothalamic-pituitary-adrenal system. The effects of the recently identified neuropeptides orexin-A and orexin-B on the hypothalamic-pituitary-adrenal (HPA) system were investigated. An in vivo system was used to assess the central effects of both orexin-A and orexin-B. Different doses of the orexins (2.8-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and plasma corticosterone was used as an index of the degree of the activation of the HPA system. Both peptides exhibited a clear dose-response action, although orexin-B proved to be less effective than orexin-A. Pretreatment with the corticotropin-releasing hormone (CRH) antagonist alpha-helical CRH9-41 completely prevented the action of the orexins. Orexin-A, orexin-B or adrenocorticotropic hormone (ACTH) was further administered intraperitoneally (i.p.). While ACTH evoked a significant adrenal response, the orexins did not influence the basal secretion. Adrenal slices, oxygenized and perifused with Krebs' solution, were also treated with orexin-A, orexin-B or ACTH. Both orexins failed to modify the release of corticosterone, but ACTH induced a marked adrenal response. This study suggests that these appetite-regulating peptides might activate the HPA system at a central level but neither orexin-A nor orexin-B appears to modulate directly the adrenal corticosterone release.

Queen Execution, Diploid Males, and Selection For and Against Polyandry in the Brazilian Stingless Bee Scaptotrigona depilis. Female mating frequency varies. Determining the causes of this variation is an active research area. We tested the hypothesis that in stingless bees, Meliponini, single mating is due to the execution of queens that make a matched mating at the complementary sex determination locus and have diploid male offspring. We studied the Brazilian species Scaptotrigona depilis. We made up 70 test colonies so that 50% (single matched mating), 25% (double mating), 12.5% (quadruple mating), or 0% (single nonmatched mating) of the emerging brood were diploid males. Queen execution following diploid male emergence was equal and high in colonies producing 50% (77% executed) and 25% (75%) diploid males versus equal and low in colonies producing 12.5% (7%) and 0% (0%) diploid males. These results show that queens that mate with two males with similar paternity suffer an increased chance of being executed, which selects against double mating. However, double mating with unequal paternity (e.g., 25∶75), which occasionally occurs in S. depilis, is selectively neutral. Single mating and double mating with unequal paternity form one adaptive peak. The results show a second adaptive peak at quadruple mating. However, this is inaccessible via gradual evolutionary change in a selective landscape with reduced fitness at double mating.

Direct on-membrane peptide mass fingerprinting with MALDI-MS of tyrosine-phosphorylated proteins detected by immunostaining. We have identified tyrosine-phosphorylated proteins on membrane from A-431 human epidermoid carcinoma cells by using detection with anti-phosphotyrosine antibody followed by PMF analysis. In there, on-membrane digestion for these protein spots was carried out on microscale region using chemical inkjet technology and the resulting tryptic digests were directly analyzed by MALDI-TOF MS. Proteins identified by a database search included phosphoproteins that are known to be markedly phosphorylated on tyrosine sites after the cells are treated with epidermal growth factor (EGF). This procedure is a rapid and easily handled approach that enables both detection and identification of phosphoproteins on a single blot membrane.

Pharmacobehavioural evidence for nitric oxide and noradrenaline interactions with ryanodine receptors during memory formation in the young chick. Impairment of nitric oxide (NO) production, ryanodine receptor (RyR) calcium channel function and adrenoceptor activation have been found to prevent the formation of the long-term memory stage in young chicks trained on a single-trial discrimination avoidance task. The current study investigated whether these three activities were linked, and if so, the sequence of activation. Young chicks were trained using either a strongly or weakly reinforced variant of the single-trial discrimination avoidance task, yielding either a persistent or labile memory trace, respectively. Following strongly reinforced training, retention loss induced by a RyR inhibitor was prevented by a NO donor or noradrenaline (NA). A RyR agonist also prevented retention loss induced by either NO synthase or β1+2-adrenoceptor inhibition. These findings were interpreted to reflect the capacity of NO, RyR-dependent calcium release and NA to modulate memory by preventing retention loss. A second set of studies used weakly reinforced training. Although the administration of a RyR agonist promoted long-term memory formation, this facilitation was compromised in the presence of a β1+2-adrenoceptor antagonist, but not a NO synthase inhibitor. Similarly, the inhibition of RyRs interfered with the facilitation of retention induced by a NO donor, but not NA. These differential findings with weakly reinforced training suggest that NO facilitates memory formation through mechanisms involving RyR-dependent calcium release. The findings also indicate that RyRs may promote memory formation through noradrenergic activation of β2-adrenoceptors. This study demonstrates an intricate role for RyRs underlying memory formation.

Defective CD3 mediated proliferation and LPS responsiveness in multiple sclerosis. Multiple sclerosis [MS] is a chronic inflammatory disease of the central nervous system which has been postulated to be a T cell mediated disease. We examined proliferation of mononuclear cells to OKT3 mAb, Con A, ionomycin plus PMA and human myelin basic protein in subjects with relapsing-remitting and chronic progressive multiple sclerosis. Age and sex matched controls demonstrated a good proliferation to anti-CD3 mAb whereas subjects with relapsing-remitting multiple sclerosis showed a significantly decreased anti-CD3 mAb response. There was no difference in mitogen, ionomycin plus PMA or human MBP proliferation between controls and MS subjects. There was also a trend for decreasing anti-CD3 mAb proliferation in patients with chronic progressive multiple sclerosis compared to controls. LPS significantly decreased anti-CD3 mAb proliferation in controls but not in the MS subjects. An abnormality of signal transduction via the CD3 T-cell receptor complex in T cells and responsiveness to the immunomodulatory effect of IFN inducers may exist in multiple sclerosis.

Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia. Recently, the neuroprotective effects of lithium against excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors have been demonstrated. Since brain ischemia results in NMDA receptor over-excitation and Src family protein tyrosine kinase-mediated tyrosine phosphorylation of NMDA receptor subunit 2A (NR2A) enhances NMDA receptor activity, we examined the effects of lithium on tyrosine phosphorylation of NR2A and its interactions with Src and Fyn (two members of the Src family of protein tyrosine kinases) mediated by PSD-95 (postsynaptic density protein 95 kDa) after 6 h of reperfusion following 15 min of ischemia (I/R), which was induced by occlusion of the four vessels in Sprague-Dawley rats. After abdominal injection of LiCl (2 mg/kg) for 7 days, the data showed that together with the significant decrease in I/R-induced tyrosine phosphorylation of NR2A, the interactions of NR2A with Src and Fyn mediated by PSD-95 were also decreased significantly. However, lithium pretreatment did not alter the total protein levels of NR2A, Src, Fyn and PSD-95. These results suggest that the inhibition of NR2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 may contribute to the lithium-induced downregulation of NMDA receptor function and provide neuroprotection against excitotoxicity.

Telemedical treatment at home of diabetic foot ulcers. The treatment of diabetic foot ulcers may not always be well organized and not all patients have access to expert evaluation. We investigated the use of telemedicine to enable a visiting nurse (in the patient's home) to coordinate the treatment with experts (at the hospital). The equipment consisted of a UMTS videophone and an Internet-based patient record. Field studies were carried out at the outpatient clinic and by following visiting nurses. A total of 15 participants were invited to five workshops and experiments held in our laboratories, at the hospital, and between hospital and patients' homes. Finally, in a pilot test, five patients were offered three teleconsultations at their homes in lieu of visits to the hospital. Preliminary results were promising: (1) both clinicians and patients found the equipment easy to use; (2) the doctor could prescribe treatment at a distance; (3) the visiting nurse had realtime contact with the hospital and treatment could begin immediately according to the doctor's orders; (4) the patient saved time in not having to travel to the hospital.

Theoretical and experimental evidence of extinction and coexistence of killer and sensitive strains of yeast grown as a mixed culture in water. Theoretical and experimental evidences of extinction and coexistence during batch interaction of killer and sensitive strains of Saccharomyces cerevisiae grown as a mixed culture in pure water are provided. The experimental results show that in the limited nutrient conditions of growth in pure water, the killer yeast is subject to extinction when the initial concentration ratio of killer to sensitive yeast is 1:100. However, if the initial concentration ratio of killer to sensitive yeast is 1:1, both strains coexist. Substantial damped oscillations are associated with the growth process in the mixed culture. A new theoretical model that was originally developed for recovering the growth of single species in isolation is extended and applied to two species competing over a common ecological niche. The solutions of the model are shown to recover all the qualitative features captured in the experiments.

Recurrent Guillain-Barré syndrome. Guillain-Barré syndrome (GBS) is generally considered to be monophasic, but recurrences do occur in a presently undefined subgroup of patients. To determine which subgroup of patients develops a recurrence and to establish whether preceding infections and neurological symptoms are similar in subsequent episodes. A recurrence was defined as two or more episodes that fulfilled the NINCDS criteria for GBS, with a minimum time between episodes of 2 months (when fully recovered in between) or 4 months (when only partially recovered). Patients with a treatment-related fluctuation or chronic inflammatory demyelinating polyneuropathy with acute onset were excluded. The clinical characteristics of recurrent GBS patients were compared with those of 476 non-recurrent patients. 32 recurrent GBS patients, who had a total of 81 episodes, were identified. The clinical symptoms in a first episode were similar to the following episodes in individual patients, being GBS or its variant Miller Fisher syndrome (MFS) but never both. While neurological symptoms in subsequent episodes were often similar, the severity of the symptoms and the nature of the preceding infections varied. Recurrent patients (mean age 34.2 years) were younger than non-recurrent patients (mean age 46.9; p = 0.001) and more often had MFS (p = 0.049) or milder symptoms (p = 0.011). Genetic or immunological host factors may play an important role in recurrent GBS, since these patients can develop similar symptoms after different preceding infections. Recurrences occur more frequently in patients under 30, with milder symptoms and in MFS.

Recent advances in functionalized micro and mesoporous carbon materials: synthesis and applications. Functionalized nanoporous carbon materials have attracted the colossal interest of the materials science fraternity owing to their intriguing physical and chemical properties including a well-ordered porous structure, exemplary high specific surface areas, electronic and ionic conductivity, excellent accessibility to active sites, and enhanced mass transport and diffusion. These properties make them a special and unique choice for various applications in divergent fields such as energy storage batteries, supercapacitors, energy conversion fuel cells, adsorption/separation of bulky molecules, heterogeneous catalysts, catalyst supports, photocatalysis, carbon capture, gas storage, biomolecule detection, vapour sensing and drug delivery. Because of the anisotropic and synergistic effects arising from the heteroatom doping at the nanoscale, these novel materials show high potential especially in electrochemical applications such as batteries, supercapacitors and electrocatalysts for fuel cell applications and water electrolysis. In order to gain the optimal benefit, it is necessary to implement tailor made functionalities in the porous carbon surfaces as well as in the carbon skeleton through the comprehensive experimentation. These most appealing nanoporous carbon materials can be synthesized through the carbonization of high carbon containing molecular precursors by using soft or hard templating or non-templating pathways. This review encompasses the approaches and the wide range of methodologies that have been employed over the last five years in the preparation and functionalisation of nanoporous carbon materials via incorporation of metals, non-metal heteroatoms, multiple heteroatoms, and various surface functional groups that mostly dictate their place in a wide range of practical applications.

A unique ascorbate peroxidase active component in the cyanobacterium Synechococcus PCC 7942 (R2). Ascorbate peroxidase active component (APAC) was purified and characterized in Synechococcus PCC 9742 (R2) cells. APAC was isolated from freshly harvested cells, by ion exchange chromatography on DEAE cellulose, ultrafiltration through a 3000 dalton cut off filter and high pressure liquid chromatography through a reversed phase C-18 column. APAC was found to be extremely stable to harsh treatments of boiling water for 30 min, acidification to pH 2.0 and proteolytic digestion. A close correlation between activity and iron content of APAC was observed throughout the purification steps. E.S.R. spectrum of APAC showed a resonance line at g = 4.3 in the oxidized from. Peroxide reduction by ascorbate decreased the E.S.R. signal, which reappeared upon reoxidation by H2O2. The affinities of APAC to H2O2 and ascorbate were high (0.38 mM and 0.2 mM, respectively). Amino acid composition analysis of APAC revealed the presence of glutamic acid:glycine:cysteine residues at 2:1:1 ratio.

Is intraspecific variation in diet and morphology related to environmental gradients? Exploring Liem's paradox in a cichlid fish. Interspecific studies have demonstrated that trophic morphology and ecology are not always tightly matched: a phenomenon rarely reported at the intraspecific level. In the present study, we explored relationships among diet, morphology and the environment in a widespread cichlid fish, Astatoreochromis alluaudi (Pellegrin 1904), from 6 sites in southern Uganda to test for evidence of eco-morphological matching at the interdemic level. Previous studies of Astatoreochromis alluaudi have demonstrated developmental plasticity in trophic morphology in response to diet: a mollusk diet produces specimens with large pharyngeal jaws and muscles, whereas a soft-food diet produces smaller pharyngeal jaws and corresponding changes in musculature. Sites were chosen to maximize variability in environmental variables that might directly or indirectly affect trophic morphology. We found significant differences in pharyngeal jaw and muscle morphology among populations. Similarly, we found differences in diets among sites: mollusks were found in the stomachs of fish from only 2 populations sampled, despite the presence of mollusks in 5 of the 6 sites. Although trophic morphology did match the observed diet in 2 sites, diet did not correlate with either morphology or environmental variables across sites, nor were environmental variables correlated with morphological variation among sites. These results suggest that mismatch can occur among different populations of a single species for reasons such as seasonality in resources, developmental plasticity and/or complex indirect interactions. Intraspecific mechanisms should be further studied in order to better understand the complex relationships between morphological specialization and ecological generalization.

Diagnosis of cerebellopontine angle tumors with small quantities of air. Difficulty in detecting small acoustic neuromas has encouraged us to study patients suspected of having a tumor by air cisternography augmented with computed tomography. Ninety patients were examined without complication. Five cubic centimeter of air was introduced via lumbar puncture and manipulated into the cerebellopontine angle cisterns. Scanning is commenced immediately. Filling of both internal auditory canals and identification of the neurovascular bundle in the cerebellopontine angle cistern was possible in all patients except those with tumors. The diagnostic accuracy, speed, and lack of morbidity have made this procedure the initial radiologic examination at our institution for patients suspected of having acoustic neuroma.

Versatile protamine nanocapsules to restore miR-145 levels and interfere tumor growth in colorectal cancer cells. MicroRNAs (miRNAs) play a key role on gene expression regulation contributing to cell homeostasis, and they are highly dysregulated in cancer. Consequently, miRNA-based therapies are an attractive approach to develop novel anticancer strategies. The main objective of this work was to explore the full potential of protamine nanocapsules (Pr NCs) to develop an anticancer therapy based on the restoration of oncosuppressor miR-145, downregulated in colorectal cancer cells. The composition of Pr NCs was defined based on the selection of surfactants, and protamine that would enable an efficient association and intracellular delivery of miRNA mimics according to the layer-by-layer approach, and the encapsulation of curcumin within the oily core. After exposure of colorectal cancer cells with (i) miR-145 and (ii) curcumin-loaded Pr NCs, a strong increase in the intracellular levels of miR-145, which translated into a decreased cell proliferation rate and migration capacity of the treated cells, was observed. The potential of exploiting Pr NCs for the co-delivery of both biomolecules, miRNAs and curcumin, has also been proved. All together, here we evaluate the possibility to use Pr NCs to efficiently increase the intracellular levels of the oncosuppressor miR-145.

Exposure to paclitaxel or vinblastine down-regulates CD11a and CD54 expression by P815 mastocytoma cells and renders the tumor cells resistant to killing by nonspecific cytotoxic T lymphocytes induced with anti-CD3 antibody. Paclitaxel and vinblastine are drugs with anti-microtubule activity that are commonly used in the treatment of numerous types of cancer. In this study, we investigated the effect of prior exposure to submaximal cytotoxic concentrations (EC(25) and EC(50)) of paclitaxel or vinblastine on the subsequent susceptibility of surviving P815 murine mastocytoma cells to cytolysis by major histocompatibility complex (MHC)-unrestricted mouse cytotoxic T lymphocytes that had been induced with anti-CD3 antibody. P815 cells that had survived culture for 24 h in the presence of paclitaxel (5 or 50 micro g/ml) or vinblastine (1.5 or 15 micro g/ml) were rendered resistant to anti-CD3-activated killer-T (AK-T) cell-mediated cytolysis in a standard (51)Cr-release assay. Resistance to killing was associated with a reduced ability of AK-T cells to form conjugates with drug-treated P815 target cells, suggesting a possible effect on adhesion molecules. Flow cytometric analysis of paclitaxel- or vinblastine-treated P815 cells revealed reduced cell-surface expression of the adhesion molecules LFA-1 (CD11a /CD18) and ICAM-1 (CD54). Similar results were obtained following paclitaxel or vinblastine treatment of Yac-1 lymphoma cells. RT-PCR analysis revealed reduced levels of mRNAs coding for CD11a and CD54 in paclitaxel- or vinblastine-pretreated P815 cells. Collectively, these data lead us to conclude that paclitaxel and vinblastine render P815 mastocytoma cells resistant to T cell-mediated cytotoxicity by interfering with CD11a and CD54 expression by the tumor cells. A similar effect by these drugs on tumor cells and/or leukocytes in cancer patients might compromise tumor-specific cell-mediated immune responses.

On the tumorigenicity of mitochondrial DNA-depleted avian cells. We have examined the tumorigenic potential of mitochondrial DNA-depleted (mtDNA-) cells derived from the tumorigenic chicken cell line DU24. The mtDNA- cells were unable to proliferate in the wing web of day-old chicks. Cytoplasmic hybrids resulting from crosses between the mtDNA- whole cells and cytoplasts from enucleated parental cells (mtDNA+) recover both mtDNA and tumorigenicity. These results are in accordance with those obtained in prior experiments where mtDNA was shown to modulate the anchorage-independent phenotype of transformed avian cells.

Externalizing Outcomes of Youth with and without ADHD: Time-Varying Prediction by Parental ADHD and Mediated Effects. Although parental attention-deficit/hyperactivity disorder (ADHD) is a risk factor for multiple negative youth outcomes, it is unknown how change in parental ADHD symptoms over time affects change in child ADHD symptoms; moreover, mediators of these predictions are largely unknown. Parents of 230 5-10 year-old children (68 % male) with (n = 120) and without ADHD (n = 110) were followed prospectively for 6-7 years across three separate waves. Parents self-reported their ADHD and depression symptoms and similarly rated offspring ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms; youth self-reported their substance use. Temporally-ordered mediators consisted of parental expressed emotion (EE), derived from the Five Minute Speech Sample, and self-reported positive and negative parenting behavior. Controlling for key demographics and parental depression symptoms, increasing parental ADHD symptoms were a time-varying predictor of worsening youth ADHD and ODD, although it was unrelated to change in CD and alcohol/substance use. Next, although EE facets (i.e., criticism, emotional over-involvement) did not mediate these predictions, negative parenting behavior significantly mediated predictions of youth ADHD (and marginally in predictions of ODD) from parental ADHD symptoms. These quasi-experimental findings suggest that parental ADHD symptoms are a potential unique causal risk factor for offspring ADHD and ODD; also, preventing negative parenting behavior secondary to parental ADHD symptoms is critical to improve trajectories of youth ADHD and ODD. We consider parental ADHD symptoms and family factors underlying emergent externalizing problems utilizing a developmental psychopathology framework, including implications for intervention and prevention.

Binding of a bZip protein to the estrogen-inducible apoVLDL II promoter. Activation of the very low density apolipoprotein II (apoVLDL II) gene in chicken liver by estrogen results in the binding of a variety of nuclear proteins including members of the steroid receptor superfamily and the bZip superfamily to the immediate 5' flanking region. In the present study, we have identified a bZip protein from chicken liver as one of the potential binding activities. Its cognate cDNA was cloned from an expression library using a recognition site DNA probe corresponding to part of the apoVLDL II promoter region. By footprinting and gel shift analysis with the recombinant protein from a prokaryotic expression system we have established that the protein binds to at least three different sites in the apoVLDLII promoter region. One of these sites partially overlaps with the major estrogen response element of the gene. Despite the proximity of their binding sites, the estrogen receptor and the bZip protein can bind simultaneously to the very region. Possible implications of this intimate arrangement of binding sites for the activation of the apoVLDL II promoter are discussed.

Computed tomography of the abdomen in evaluation of patients with fever of unknown origin. Applying Petersdorf's classic criteria for fever of unknown origin (FUO), 75 of 6,654 CT scans were reviewed to evaluate the diagnostic effectiveness of abdominal CT. Twenty-three (29%) of these 78 scans had positive CT findings and 8 (10%) had positive but nonspecific findings. Abdominal exploration or biopsy was carried out in 20 of these 31 patients. In addition, 10 cases with negative CT results were explored. In no case was any gross anatomic abnormality found in these negative cases.

[Glucose intolerance and post-stimulatory hypoglycemia secondary to a probably congenital intrahepatic portacaval anastomosis]. Recurrent malaise in a 63 year old woman were found to be due to hypoglycaemic episodes. During a 5 hour oral glucose tolerance test, the "impaired glucose tolerance" type initial hyperglycaemic wave was followed by a post-stimulative hypoglycaemia. Serum C-peptide levels were normal during the test, but the insulin response which was initially normal became excessive, with a consequent decrease of the C-peptide/insulin ratio, similar to that usually observed in hepatic malfunction. An hepatic ultrasonography, a cavography and a selective superior mesenteric arteriography showed an intra-hepatic porto-caval anastomosis, probably congenital in origin. This vascular abnormality accounts for the blood glucose problems: the porto-caval shunt explains the early hyperglycaemia by defective liver uptake of glucose and secondary hyperinsulinism occurs because of the reduced hepatic degradation of the insulin secreted in normal quantity. The late hyperinsulinism then leads to secondary hypoglycaemia.

Sex differences in visual-spatial working memory: A meta-analysis. Visual-spatial working memory measures are widely used in clinical and experimental settings. Furthermore, it has been argued that the male advantage in spatial abilities can be explained by a sex difference in visual-spatial working memory. Therefore, sex differences in visual-spatial working memory have important implication for research, theory, and practice, but they have yet to be quantified. The present meta-analysis quantified the magnitude of sex differences in visual-spatial working memory and examined variables that might moderate them. The analysis used a set of 180 effect sizes from healthy males and females drawn from 98 samples ranging in mean age from 3 to 86 years. Multilevel meta-analysis was used on the overall data set to account for non-independent effect sizes. The data also were analyzed in separate task subgroups by means of multilevel and mixed-effects models. Results showed a small but significant male advantage (mean d = 0.155, 95 % confidence interval = 0.087-0.223). All the tasks produced a male advantage, except for memory for location, where a female advantage emerged. Age of the participants was a significant moderator, indicating that sex differences in visual-spatial working memory appeared first in the 13-17 years age group. Removing memory for location tasks from the sample affected the pattern of significant moderators. The present results indicate a male advantage in visual-spatial working memory, although age and specific task modulate the magnitude and direction of the effects. Implications for clinical applications, cognitive model building, and experimental research are discussed.

[Advances in new type of biomolecular markers for liver fibrosis]. Liver fibrosis is a common pathological process of chronic liver disease, and the number of deaths from liver cirrhosis, liver failure and liver cancer is increasing year-by-year worldwide. Presently, the detection methods to evaluate hepatic fibrosis mainly include hepatic histological examination, imaging and serum markers, but all these have many limitations in clinical aspects. Recently, there have been more and more studies related to the development of non-coding RNA, exosomes and liver fibrosis that are considered as a new type of biomolecular markers with potential clinical application. Herein, we did a preliminary assessment in conjunction with relevant advances to provide a reference for the early diagnosis and treatment of liver fibrosis.

Structure-aided optimization of 3-O-β-chacotriosyl ursolic acid as novel H5N1 entry inhibitors with high selective index. Currently, entry inhibitors contribute immensely in developing a new generation of anti-influenza virus drugs. Our earlier studies have identified that 3-O-β-chacotriosyl ursolic acid (1) could inhibit H5N1 pseudovirus by targeting hemagglutinin (HA). In the present study, a series of C-28 modified pentacyclic triterpene saponins via conjugation with a series of amide derivatives were synthesized and their antiviral activities against influenza A/Duck/Guangdong/99 virus (H5N1) in MDCK cells were evaluated. The SARs analysis of these compounds revealed that introduction of certain amide structures at the 17-COOH of ursolic acid could significantly enhance both their antiviral activity and selective index. This study indicated that the attachment of the methoxy group or Cl atom to the phenyl ring at the ortho- or para-position was crucial to improve inhibitory activity. Mechanism studies demonstrated that these title triterpenoids could bind tightly to the viral envelope HA to block the attachment of viruses to host cells, which was consistent with docking studies.

Integral modeling approach to study the phase behavior of complex solids: application to phase transitions in MgSiO3 pyroxenes. A combination of electronic structure calculations, classical molecular dynamics simulations and metadynamics is proposed to study the phase behavior of complex crystals. While the former provide accurate energetics for thermodynamic properties, molecular dynamics and metadynamics simulations may reveal new metastable phases and provide insight into mechanisms and kinetics of the respective structural transformations. Here, different simulation methods are used to investigate the polymorphism of MgSiO(3) pyroxenes (enstatites) up to high pressures and temperatures. A number of displacive phase transitions are observed within the three basic structure types clino-, ortho- and protoenstatite using classical molecular dynamics simulations. Transitions between these types require a change of stacking order, which is modeled using a combination of molecular dynamics and metadynamics.

Neighborhood Socioeconomic Status and Health Care Costs: A Population-Wide Study in the Netherlands. Objectives. To identify disparities in several types of insured health care costs in the Netherlands across neighborhoods with different socioeconomic statuses and to assess the room for improvement. Methods. We used 2015 Dutch whole-population registry data to estimate the age- and gender-specific cost structure by neighborhood for total, specialist, pharmaceutical, and mental health care. Classifying neighborhoods by the quintile of their neighborhood socioeconomic status (NSES), we determined differences in observed and expected health care costs for several scenarios of NSES improvement. Results. From low to high NSES, we found a clear downward gradient in health care costs. Total health care costs would drop by 7.3% if each neighborhood's cost structure was equal to that of the most affluent neighborhoods. The potential for cost reduction appeared highest for females, for age groups between 40 and 60 years, and for pharmaceutical care. Conclusions. Low NSES is associated with relatively high health care costs, and represents considerable potential for cost savings in health care. Public Health Implications. Our research suggests that policies aimed at improving the socioeconomic determinants of health locally may be pivotal in containing health care costs.

[A Case of Rectal Cancer with Portal Vein Tumor Thrombosis Successfully Treated with First-Line Panitumumab Monotherapy]. The patient was a 66-year-old man with progressive rectal cancer and portal vein tumor thrombosis near the porta hepatis. A subileus further complicated the situation. Therefore, an abdominoperineal resection was performed. As the KRAS gene was the wild-type gene, we administered panitumumab monotherapy every 2 weeks after the operation. Two months after the operation, the tumor marker levels were normal and the tumor size was reduced. Hence, oral capecitabine, with 1-week administration followed by 1-week of rest, was added to the therapy. In the 12 months after the operation, panitumumab was stopped once, and treatment with capecitabine alone was continued in the same schedule. As of 26 months, the disease showed a partial response using capecitabine alone. We report our experience of a case of rectal cancer with portal vein tumor thrombosis that was successfully treated with panitumumab.

Use of oral creatine as an ergogenic aid for increased sports performance: perceptions of adolescent athletes. Competitive athletes, including adolescents, seek ways to gain advantage over competitors. One ergogenic aid is creatine, a naturally occurring nitrogen compound found primarily in skeletal muscle. Increasing creatine levels may prolong skeletal muscle activity, enhancing work output. A questionnaire assessing awareness and use of creatine supplementation was completed by 674 athletes from 11 high schools. Data were statistically analyzed to determine variation among groups. Of those surveyed, 75% had knowledge of creatine supplements, and 16% used creatine to enhance athletic performance. Percentage of use increased with age and grade level. Awareness and use were greater among boys than girls. Adverse effects were reported by 26%. Most athletes consumed creatine using a method inconsistent with scientific recommendations. Use of creatine by adolescent athletes is significant and inconsistent with optimal dosing. Physicians, athletic trainers, and coaches should disseminate proper information and advise these adolescent athletes.

Latex allergy: allergen identification in Hevea braziliensis fractions by immunoblotting. Latex is the cause of several clinical symptoms of allergy, but the identification of allergens is not completely known. The aim of this report was to study the immunoreactivity of purified stable latex fractions from Hevea braziliensis. We purified the cytoplasm of Hevea braziliensis and obtained three fractions: latex particles (LP), lutoids (L) and cytosolic serum (CS). Using Western blot, specific IgE directed to latex allergens was found in 80 patients with latex allergy. Five major groups of allergens migrating as 14, 25, 29, 37-45 and 50 kDa were recognized. They were unequally distributed with the latex fractions: 37-45 kDa proteins were essentially recognized in CS and LP, whereas 14 and 29 kDa proteins were mainly labelled in the L fraction. As a control, aqueous glove extracts exhibited a more restricted pattern of reactivity, because only 14 and 29 kDa proteins were recognized by patient sera. The pattern of reactivity was not correlated specifically with IgE levels, but sera from patients suffering from spina bifida reacted specifically with the minor protein of 25 kDa located in LP. The present results show that latex allergic patients recognize several allergens which are differently distributed in subcellular fractions extracted from H. braziliensis and aqueous GE. The L fraction and GE were enriched in low molecular weight proteins and apparently contained the same allergens.