Ellucidating the incidence and the prevalence of Schistosomiasis spp infection in riparian communities of the Bui dam.
The flow rate of rivers are affected when modifications are made for the benefit of mankind. Some man-made alterations carried out include dam construction. The aim of this study was to investigate the health impact of the Bui dam with respect to the prevalence and awareness level of schistosomiasis in a typical damming environment. The study was conducted in 4 riparian communities within the dam catchment area. A cross-sectional study design was employed to interview 350 individuals. Urine and stool samples were also collected from 386 participants. Results of the study showed that, knowledge of schistosomiasis was significantly greater in close communities (99.47%) than their far counterparts (50.29%) (p > 0.001; OR = 172). Schistosomiasis infection rate in the close communities (32.57%) were significantly greater in far communities (7.23%; p ≤ 0.0001). The overall prevalence of 82 (21.1%) was recorded for Schistosoma haematobium and 64 (16.1%) for Schistosoma mansoni. A significantly high prevalence of S. haematobium (43.3%) was found in the age group 15-24 with no prevalence reported for age group 5-9 (Close communities) (p = 0.012). When the same age group was further examined for S. mansonii, group 5-9 recorded a prevalence of 0% with age group 10-14 showing a high prevalence of 26.1% (p = 0.047). From the study, it was concluded that, though awareness level of Schistosomiasis knowledge on the cause, mode of transmission and symptoms were high, they were ignorant on personal preventive strategies. In addition, the study also revealed that, S. haematobium was more prevalent among inhabitants living closer to the Bui dam with children less than 14 years of age being the worst affected.


The induction of interferon by temperature-sensitive mutants of Sindbis virus: its relationship to double-stranded RNA synthesis and cytopathic effect.
Sindbis virus strain AR339 induces interferon by 3 h after infection at 39 degrees C and by 8 h after infection at 30 degrees C. The time course of interferon induction between 4 and 9 h after infection at the restrictive temperature (39 degrees C) was measured for 24 temperature-sensitive (ts) mutants, all of which induced interferon by 16 h after infection. Mutants showing total RNA synthesis at 39 degrees C greater than 10% of the wild-type level induced interferon with kinetics similar to the wild-type. Of those mutants showing 1 to 10% of the wild-type level of RNA synthesis at 39 degrees C, four induced interferon with kinetics similar to the wild type, whereas six showed a lag in induction. Nine mutants, showing 0 to 5% of the wild-type level of RNA synthesis at 39 degrees C, and the wild type, were examined for single and double-stranded RNA synthesis at 30 and 39 degrees C, using a combination of lithium chloride precipitation and CF11 cellulose chromatography. Six of these mutants showed a lag in interferon induction at 30 degrees C, while three showed no lag. For all nine mutants, double-stranded RNA synthesis at 39 degrees C was undetectable, although easily detectable for the wild type. Both the wild type and the mutants synthesized double-stranded RNA at 30 degrees C. For all mutants, time of interferon induction at 39 degrees C was correlated with c.p.e. as measured by trypan blue uptake 30 h after infection. The mutant F104, showing undetectable RNA synthesis and a long lag in interferon induction at 39 degrees C, was examined for interferon induction in a temperature shift system. Only 1/2 h at 30 degrees C, before a shift to 39 degrees C, was required for interferon to be induced with wil-type kinetics, and this was correlated with an increased c.p.e. 30 h after infection. Increased RNA synthesis and infectious virus production were detectable at 30 degrees C after an initial hour at 30 degrees C. It is concluded that, for interferon to be induced with normal kinetics, early virus functions are required, but that normal levels of double-stranded RNA synthesis are not necessary. The events which lead to interferon induction also lead to visible c.p.e.


Reflex inhibition of the slowly adapting stretch receptors in the intact abdomen of the crayfish.
The reflex inhibition of abdominal stretch receptors in crayfish was studied by controlled passive flexion of individual abdominal joints. The results are very similar to those obtained by electrical or mechanical stimulation of individual stretch receptors in immobilized abdomens. Reflex effects from posterior to anterior abdominal segments are somewhat stronger than in the opposite direction. Flexion of one abdominal joint excites the stretch receptors of that joint and inhibits the stretch receptors in neighbouring abdominal segments. Without reflex inhibition flexion of one abdominal joint excites the stretch receptors in several abdominal segments.


Malnutrition after bariatric surgery.
Malnutrition is a rare but severe complication following obesity surgery. Our objective was to analyze these cases of malnutrition and their management at the Grenoble University Hospital. Retrospective data between 2006 to 2016 was analyzed from Department of Medical Information, Severe Obesity Outcome Network, and register of the Department of Artificial Nutrition. Data collected concerned age, sex, anthropometric data, surgical procedures and history of obesity surgery, initial surgical follow-up, delay from surgery, nutritional characteristics, nutritional and surgical management, follow-up and outcomes. Six patients had protein malnutrition after obesity surgery. Five patients (N.=5/6 83%) were initially operated on in other establishments. Only 1 patient in the cohort of 484 patients operated at on our institution was suffering from malnutrition (N.=1/484, 0.2%). All patients showed an excess weight loss of over 100%. Albumin level averaged 24.8 g/L at time of diagnosis. Patients were mainly operated on for an omega bypass (N.=4/6, 66%). Delay of malnutrition was 17.25 months in this category of patients whereas it was 84 months in patients having been operated on by another intervention. 3 patients (i.e. 50%) had chronic kidney disease when their initial surgery was performed. Two patients presented acute idiopathic pancreatitis following obesity surgery. Patients are at risk of malnutrition, especially after omega bypass and in patients with chronic kidney disease. Occurrence of acute pancreatitis is an alert to the risk of malnutrition.


Inhibition of substance P activity prevents stress-induced bladder damage.
Substance P is a neuropeptide involved in inflammation, immune regulation and stress response. Stress may induce bladder damage by stimulating inflammatory response such as mast cell activation. We here examined the role substance P during stress-induced mast cell degranulation and urothelial injury in rat bladder. Adult Sprague-Dawley rats (200-270 g) were either exposed to cold-immobilization stress or substance P (SP) intracerebroventricularly. Different doses of substance P receptor (NK1R) antagonist CP 99994 were administered peripherally or centrally before the stress exposure. From each group, samples of the bladder were examined with light and electron microscope. Stress- and SP-injected centrally, increased the number of both granulated and degranulated mast cells. Ultrastructurally, urothelial degeneration with vacuolization in the cytoplasm and dilated intercellular spaces were seen. Both central and peripheral injection of CP 99994 prevented stress-induced urothelial degeneration as well as stress-induced mast cell degranulation. In conclusion, centrally and peripherally released substance P is involved in stress-induced bladder damage. Inhibition of NK1R prevents stress-induced pathological changes of urinary bladder and NK1R antagonist can be considered for the treatment of inflammatory bladder diseases.


The role of nutritional interventions in increasing fruit and vegetable intake in the elderlies: a systematic review.
The consumption of fruit and vegetables in old ages is particularly important, so that the appropriate consumption amount leads to reduction in the risk of chronic diseases. To increase consumption of fruit and vegetables and modify consumption pattern in the elderlies, training programs and appropriate intervention can be designed and implemented. The study was done to assess and compare nutritional intervention-based training methods and education using theories and health education models for the consumption of fruits and vegetables in the elderlies. Electronic search using keywords of Country Review Information Bank (Magiran), Scientific Information Database, Pub Med, Science direct, Science, Biomed central from the beginning of March 2014 to end of April 2015 was performed. Ten interventional studies were assessed in this systematic study. The interventions were divided into two groups of studies, a total of five studies, theories and health education models were the basis of training intervention and the other five studies that include their interventions without the use of theories and health education models was carried out. Of ten interventional studies, three studies as before and after and seven studies as the intervention and control was performed. The results showed that education-based theory and health education models have a greater impact on the consumption of fruit and vegetables in the elderlies. The duration and interventions performing method, environmental factors and educational programs using appropriate models and theories are important on the effectiveness of interventions to increase consumption of fruit and vegetables in the elderliness.


Cistanche tubulosa phenylethanoid glycosides induce apoptosis in Eca-109 cells via the mitochondria-dependent pathway.
Cistanche tubulosa has various biological functions. In the present study, the antitumor effect of water-soluble phenylethanoid glycosides of C. tubulosa (CTPG-W) on esophageal cancer was investigated. Eca-109 cells were treated with CTPG-W and the cell viability was measured by MTT assay. The apoptosis, cell cycle, mitochondrial membrane potential (Δψm) and reactive oxygen species were analyzed by flow cytometry. The levels of proteins in apoptotic pathways were detected by western blot analysis. It was determined that CTPG-W significantly reduced the viability of Eca-109 cells through the induction of apoptosis and cell cycle arrest. Following CTPG-W treatment, the Δψm of Eca-109 was notably decreased, which is associated with the upregulated levels of B-cell lymphoma-2 (Bcl-2)-associated X and downregulated levels of Bcl-2. Consequently, the levels of cytochrome c and c-Jun NH2-terminal kinase were increased, which upregulated the levels of cleaved-poly (ADP-ribose) polymerase and cleaved-caspase-3, -7 and -9, but not caspase-8. Correspondingly, the levels of reactive oxygen species in Eca-109 cells demonstrated notable changes. These results indicated that CTPG-W induced apoptosis of Eca-109 cells through a mitochondrial-dependent pathway.


PREDNOD, a prediction server for peptide binding to the H-2g7 haplotype of the non-obese diabetic mouse.
The non-obese diabetic (NOD) mouse is a widely used animal model for study of autoimmune diseases, in particular human type 1 diabetes mellitus (T1DM). Identification of the subset of peptides that bind MHC molecules comprising the H-2g7 haplotype of NOD mouse and thereby representing potential NOD T-cell epitopes is important for research into the pathogenesis and immunotherapy of T1DM. The H-2g7 haplotype comprises the MHC class-I molecules Kd and Db and a single class-II molecule I-Ag7. We have developed a prediction system, PREDNOD, for accurate identification of peptides that bind the MHC molecules constituting the H-2g7 haplotype. PREDNOD is accessible at http://antigen.i2r.a-star.edu.sg/Ag7.


Outcomes of a Failure Mode and Effects Analysis for medication errors in pediatric anesthesia.
The Institute of Medicine has called for development of strategies to prevent medication errors, which are one important cause of preventable harm. Although the field of anesthesiology is considered a leader in patient safety, recent data suggest high medication error rates in anesthesia practice. Unfortunately, few error prevention strategies for anesthesia providers have been implemented. Using Toyota Production System quality improvement methodology, a multidisciplinary team observed 133 h of medication practice in the operating room at a tertiary care freestanding children's hospital. A failure mode and effects analysis was conducted to systematically deconstruct and evaluate each medication handling process step and score possible failure modes to quantify areas of risk. A bundle of five targeted countermeasures were identified and implemented over 12 months. Improvements in syringe labeling (73 to 96%), standardization of medication organization in the anesthesia workspace (0 to 100%), and two-provider infusion checks (23 to 59%) were observed. Medication error reporting improved during the project and was subsequently maintained. After intervention, the median medication error rate decreased from 1.56 to 0.95 per 1000 anesthetics. The frequency of medication error harm events reaching the patient also decreased. Systematic evaluation and standardization of medication handling processes by anesthesia providers in the operating room can decrease medication errors and improve patient safety.


Estimating psychological networks and their accuracy: A tutorial paper.
The usage of psychological networks that conceptualize behavior as a complex interplay of psychological and other components has gained increasing popularity in various research fields. While prior publications have tackled the topics of estimating and interpreting such networks, little work has been conducted to check how accurate (i.e., prone to sampling variation) networks are estimated, and how stable (i.e., interpretation remains similar with less observations) inferences from the network structure (such as centrality indices) are. In this tutorial paper, we aim to introduce the reader to this field and tackle the problem of accuracy under sampling variation. We first introduce the current state-of-the-art of network estimation. Second, we provide a rationale why researchers should investigate the accuracy of psychological networks. Third, we describe how bootstrap routines can be used to (A) assess the accuracy of estimated network connections, (B) investigate the stability of centrality indices, and (C) test whether network connections and centrality estimates for different variables differ from each other. We introduce two novel statistical methods: for (B) the correlation stability coefficient, and for (C) the bootstrapped difference test for edge-weights and centrality indices. We conducted and present simulation studies to assess the performance of both methods. Finally, we developed the free R-package bootnet that allows for estimating psychological networks in a generalized framework in addition to the proposed bootstrap methods. We showcase bootnet in a tutorial, accompanied by R syntax, in which we analyze a dataset of 359 women with posttraumatic stress disorder available online.


Kirkwood-Buff theory of four and higher component mixtures.
Explicit expressions are developed for the chemical potential derivatives, partial molar volumes, and isothermal compressibility of solution mixtures involving four components at finite concentrations using the Kirkwood-Buff theory of solutions. In addition, a general recursion relationship is provided which can be used to generate the chemical potential derivatives for higher component solutions.


Mifepristone-induced abortion and placental complications in subsequent pregnancy.
The aim of the study was to explore the effect of first-trimester mifepristone-induced abortion (MA) on placental complications in subsequent pregnancy. Two cohorts of nulliparous pregnant women were recruited in China during early pregnancy, one with a history of one MA and the other with no abortion (NA). Women were followed up until delivery. The incidence proportions of abruptio placenta, placenta previa, placenta accreta and retained placenta in the MA group (4673) and NA group (4690) were, respectively, 0.5 and 0.3, 0.8 and 0.9, 0.5 and 0.5, and 0.7 and 0.8% (all differences non-significant). After adjustment for center, age, education, occupation, residence, income, BMI and type of delivery, the incidence rates of placenta previa, accreta and retained placenta in the MA and NA groups showed no significant differences. The risk of abruptio placenta in women with a MA was nearly double that of women with no abortion, although this apparent increased risk was not statistically significant. Furthermore, this increased risk of abruptio placenta was found only in those with a gestational age >6 weeks at abortion (aOR: 2.46; 95% CI: 1.00-6.04), a curettage after abortion (aOR: 3.00; 95% CI: 1.25-7.20) or a longer inter-pregnancy interval (P-value for trend: 0.022). Mifepristone-induced abortion itself is not associated with placental complications in subsequent pregnancy, but other factors related to medical abortion-such as a gestational age >6 weeks at abortion, a curettage after abortion, and a longer interpregnancy interval-may increase the risk of abruptio placenta.


Gene transfer into skeletal muscles by isogenic myoblasts.
The best way to overcome immunorejection in heterologous myoblast transfer (HMT) is by the use of immunodeficient and/or highly immunosuppressed mice as hosts. The same may be attained by autologous myoblast transfer (AMT). In this paper, we describe myoblast transfer in mdx and normal mice where the donor myogenic cells originated from highly inbred litter mates that are considered to be isogenic and thus the procedure is analogous to AMT. The myoblasts were marked in vitro with Rous Sarcoma Virus (RSV)-luciferase (Lux) or RSV-beta-galactosidase (LacZ) reporter genes through transduction mediated by an autonomously replication-defective recombinant human adenovirus. This permitted us to follow their fate after transplantation. mdx and normal mice were irradiated with 20 Gray gamma rays; necrosis and regeneration were induced by intramuscular notexin prior to myoblast injection. In both mdx and normal mice, the expression of luciferase rapidly declined after the injection implying that a large portion of the injected myoblasts were lost by 48 hr, due to undetermined cause(s). The surviving, injected myoblasts well-mosaicized large groups of host fibers but only in the immediate vicinity of the injection. Substantial expression of the reporter gene continued up to 1 month post-transplantation in normal mice, but there was a gradual decline and eventual disappearance of the reporter gene expression in mdx mice. This latter phenomenon was due to the ongoing intense necrosis of muscle fibers in mdx. There was no evidence of immunorejection. These experiments indicate that even in the absence of immunorejection, myoblast transfer suffers from important negative features: major loss of myoblasts within 48 hr after the injection and lack of significant spread of the injected cells from the injection site in the host muscle. These factors, plus the limited proliferative and fusion capacity of Duchenne muscular dystrophy (DMD) myoblasts, make them less than an ideal vector for the dystrophin cDNA for dystrophin gene replacement therapy in DMD.


Subcutaneous Implantation of Hepatocellular Carcinoma in a Dog.
A 13-year-old male neutered Cocker Spaniel mixed-breed dog developed a subcutaneous mass 2 years after undergoing surgery to remove a hepatocellular carcinoma. An approximately 4 × 3 cm subcutaneous mass was found on the ventral abdomen at the cranial end of the abdominal incision from the previous surgery. The subcutaneous mass was surgically removed and histopathological examination determined that it was an implantation of the previously excised hepatocellular carcinoma. The diagnosis was confirmed by immunohistochemical labelling with hepatocyte paraffin 1 antibody and pancytokeratin. Based on the location of the subcutaneous mass at the cranial end of the abdominal incision associated with the previous hepatocellular carcinoma resection, it is likely there was iatrogenic metastasis from the primary tumour excision. Subcutaneous iatrogenic metastasis of hepatocellular carcinoma is well recognized in humans but has apparently never been reported in dogs. Clinicians should be aware of this potential surgical complication.


Chemistry, manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers.
With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs.


Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis.
Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or indirect hemagglutination assays. Agreement in at least two tests must be obtained due to parasite wide antigenic variability. These techniques require equipped labs and trained personnel and are not available in distant regions. As a result, many infected people often remain undiagnosed until it is too late, as the two available chemotherapies show diminished efficacy in the advanced chronic stage. Easy-to-use rapid diagnostic tests have been developed to be implemented in remote areas as an alternative to conventional tests. They do not need electricity, nor cold chain, they can return results within an hour and some even work with whole blood as sample, like Chagas Stat-Pak (ChemBio Inc.) and Chagas Detect Plus (InBIOS Inc.). Nonetheless, in order to qualify a rapidly diagnosed positive patient for treatment, conventional serological confirmation is obligatory, which might risk its start. In this study two rapid tests based on distinct antigen sets were used in parallel as a way to obtain a fast and conclusive Chagas disease diagnosis using whole blood samples. Chagas Stat-Pak and Chagas Detect Plus were validated by comparison with three conventional tests yielding 100% sensitivity and 99.3% specificity over 342 patients seeking Chagas disease diagnosis in a reference centre in Sucre (Bolivia). Combined used of RDTs in distant regions could substitute laborious conventional serology, allowing immediate treatment and favouring better adhesion to it.


Diastereoselective [3 + 2] vs [4 + 2] Cycloadditions of Nitroprolinates with α,β-Unsaturated Aldehydes and Electrophilic Alkenes: An Example of Total Periselectivity.
Diastereoselective multicomponent reactions of enantioenriched 4-nitroprolinates, obtained by enantiocatalyzed 1,3-dipolar cycloaddition (1,3-DC) of imino esters and nitroalkenes, with α,β-unsaturated aldehydes and electrophilic alkenes proceed with total periselectivity depending on the structure of the aldehyde employed. This process evolves through a [3 + 2] 1,3-DC when cinnamaldehyde is used in the presence of an azomethine ylide, giving the corresponding highly substituted pyrrolizidines with endo selectivity. However, in the case of the α,β-unsaturated aldehyde, which contains a hydrogen atom at the γ position, an amine-aldehyde-dienophile (AAD) [4 + 2] cycloaddition takes place by formation of an intermediate 1-amino-1,3-diene, affording highly functionalized cyclohexenes with high endo diastereoselectivity. This AAD process only occurred when a nitro group is bonded to the 4-position of the initial enantiomerically enriched pyrrolidine ring. DFT calculations have been carried out with the aim of explaining this different behavior between pyrrolidines with or without a nitro group, demonstrating the strong nitro-group-dependent periselectivity. The results of these computational studies also support the experimentally obtained absolute configuration of the final adducts.


ZINC 15--Ligand Discovery for Everyone.
Many questions about the biological activity and availability of small molecules remain inaccessible to investigators who could most benefit from their answers. To narrow the gap between chemoinformatics and biology, we have developed a suite of ligand annotation, purchasability, target, and biology association tools, incorporated into ZINC and meant for investigators who are not computer specialists. The new version contains over 120 million purchasable "drug-like" compounds--effectively all organic molecules that are for sale--a quarter of which are available for immediate delivery. ZINC connects purchasable compounds to high-value ones such as metabolites, drugs, natural products, and annotated compounds from the literature. Compounds may be accessed by the genes for which they are annotated as well as the major and minor target classes to which those genes belong. It offers new analysis tools that are easy for nonspecialists yet with few limitations for experts. ZINC retains its original 3D roots--all molecules are available in biologically relevant, ready-to-dock formats. ZINC is freely available at http://zinc15.docking.org.


Dynamics of intracellular free Mg2+ changes in a vascular smooth muscle cell line.
Intracellular free Mg2+ concentration ([Mg2+]i) has been implicated in the pathogenesis of hypertension. It has been postulated that Mg2+ through its antagonistic effects on intracellular Ca2+ concentration may affect tension and contractility of vascular smooth muscle cells. An established cell line of rat thoracic aorta cells (A10) was cultured on glass cover slips, and [Mg2+]i was determined by fluorescent techniques on single cells with the use of mag-fura-2. Basal [Mg2+]i was 0.52 +/- 0.02 mM (n = 15). Vascular smooth muscle cells were challenged with A23187 plus 5 mM MgCl2 to rapidly elevate [Mg2+]i. [Mg2+]i increased to a peak of 1.03 +/- 0.09 mM within 1-2 s and then quickly declined to below basal levels, 0.30 +/- 0.03 mM, within 45-60 s despite the continued presence of A23187 and external Mg2+. The rapid removal of the Mg2+ challenge to below basal levels suggests the presence of intracellular transport mechanisms, likely in intracellular compartments or organelles. Spatial imaging studies indicated that Mg2+ is heterogeneously distributed within the cell with the greatest variations in the perinuclear region, the area of most cytosolic organelles. Vanadate, an inhibitor of P-type adenosinetriphosphatases, inhibited the removal rate from 10.2 +/- 0.9 to 6.8 +/- 1.0 microM/s. Inhibitors of intracellular Ca2+ mobilization, thapsigargin, dantrolene, and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, inhibited Mg2+ sequestration. Ryanodine and caffeine had no effect on Mg2+ removal. Ruthenium red did not inhibit Mg2+ sequestration, but oligomycin B slowed its removal. These studies demonstrated that [Mg2+]i in vascular smooth muscle cells is carefully controlled by active mechanisms involving intracellular and plasma membrane transporters.(ABSTRACT TRUNCATED AT 250 WORDS)


Penetration of misonidazole after intravesical administration in cases of carcinoma of the bilharzial bladder.
The penetration of misonidazole was studied by a semiquantitative T.L.C. method after intravesical administration 2 h before total cystectomy in cases of carcinoma of the Bilharzial bladder. In 5 out of 7 cases misonidazole was found at a concentration of the order of 0.4 mg/g in the superficial and deep parts of the tumour, but not in normal bladder tissues.


Reasons for discharge from methadone maintenance for addicts at high risk of HIV infection or transmission.
This article reports on a methadone maintenance program that had the goal of retaining in treatment heroin addicts at high risk of HIV infection and/or transmission. Subjects were recruited from four-high-risk target groups and randomly assigned to either an enhanced or standard methadone maintenance group. The analysis examined predictors of any type of discharge, negative discharge, and circumstantial discharge. Discharge for any reason was more likely for younger individuals, sex industry workers, and high-risk sex partners. Legal supervision at intake and coercion into treatment reduced the probability of discharge for any reason. HIV-positive individuals were more likely to discharge for circumstantial reasons than negative reasons. The probability of circumstantial discharge was increased for males, individuals reporting suicidal ideation, and those scoring higher on an impulse expression scale. The likelihood of circumstantial discharge was decreased for individuals who reported more sources of legal income or who lived someone using illegal drugs. Participation in the enhanced treatment group appeared to reduce the probability of negative, compared with circumstantial, discharge. The findings should assist methadone treatment providers in targeting individuals at high probability of discharge for special efforts to increase treatment retention and to reengage them back into treatment after discharge, as part of a harm-reduction strategy to minimize risks of HIV infection and/or transmission.


[Preliminary data concerning cross-reacting anticardiolipin antibodies as potential inhibiting endotoxin activity factors].
In analyzed synovial fluids, suspected for endotoxin presence, the presence of endotoxin done was proved by LAL-test in 21 synovial fluids /42%/ and in 12 of 20 /60%/ the presence of endotoxin inhibiting substances /IS/ was proved. Because many parameters /like presence CIC, anti-LPS, KDO/ indicates that in the group of LAL-negative /IS/ - positive synovial fluids the presence of endotoxin is very possible, IS have been removed /by heating to 100 degrees C/ and after that the endotoxin activity was shown in about 27% of synovial fluids. Additional analysis of the Cohn fraction /prepared by ammonium sulfate precipitation/ confirmed the presence in the gamma and alpha and beta fractions a weak IS activity /in a dose dependent manner. No IS activity, have been shown yet in the fraction of affinity purified aCl antibodies.


Molecular signature of anastasis for reversal of apoptosis.
Anastasis (Greek for "rising to life") is a cell recovery phenomenon that rescues dying cells from the brink of cell death. We recently discovered anastasis to occur after the execution-stage of apoptosis in vitro and in vivo. Promoting anastasis could in principle preserve injured cells that are difficult to replace, such as cardiomyocytes and neurons. Conversely, arresting anastasis in dying cancer cells after cancer therapies could improve treatment efficacy. To develop new therapies that promote or inhibit anastasis, it is essential to identify the key regulators and mediators of anastasis - the therapeutic targets. Therefore, we performed time-course microarray analysis to explore the molecular mechanisms of anastasis during reversal of ethanol-induced apoptosis in mouse primary liver cells. We found striking changes in transcription of genes involved in multiple pathways, including early activation of pro-cell survival, anti-oxidation, cell cycle arrest, histone modification, DNA-damage and stress-inducible responses, and at delayed times, angiogenesis and cell migration. Validation with RT-PCR confirmed similar changes in the human liver cancer cell line, HepG2, during anastasis. Here, we present the time-course whole-genome gene expression dataset revealing gene expression profiles during the reversal of apoptosis. This dataset provides important insights into the physiological, pathological, and therapeutic implications of anastasis.


Histopathological changes in dental pulp of rats following radiotherapy.
Radiotherapy is one of the oral and pharyngeal cancer treatment methods that can cause damage to the tissues in the radiation area; the purpose of this study is to evaluate the effects of radiotherapy on dental pulp tissue in rats. In this interventional, experimental double-blind study, 30 rats were studied in three groups (n = 10 each). The first group received 12 gray (Gy), the second group received 18 Gy in one session, and the third group was not exposed to radiation (control group). The 5 μm sections of mandibular molar tooth were prepared and stained with hematoxylin and eosin. Samples were studied under optical microscope to evaluate and score inflammation, necrosis, hyalinization, and vascular congestion. The data were coded and analyzed by statistical tests of χ2 and Fisher's exact tests. The significant level of P = 0.05. In Group 1, necrosis in two cases, inflammation in one case, hyalinization in one case, and vascular congestion in four cases were observed. In Group 2, inflammation in four cases, hyalinization in two cases, and vascular congestion in five cases were observed. In Group 3, inflammation was observed only in one case. In comparison between the groups, no significant differences were observed in inflammation (P > 0.05), necrosis (P > 0.05), and hyalinization (P > 0.05). However, the difference was significant for vascular congestion (P < 0.05). Radiotherapy with doses of 12 and 18 Gy had no significant effect on inflammation, necrosis, and hyalinization in all groups; however, the difference was significant for vascular congestion.


Heritable and precise zebrafish genome editing using a CRISPR-Cas system.
We have previously reported a simple and customizable CRISPR (clustered regularly interspaced short palindromic repeats) RNA-guided Cas9 nuclease (RGN) system that can be used to efficiently and robustly introduce somatic indel mutations in endogenous zebrafish genes. Here we demonstrate that RGN-induced mutations are heritable, with efficiencies of germline transmission reaching as high as 100%. In addition, we extend the power of the RGN system by showing that these nucleases can be used with single-stranded oligodeoxynucleotides (ssODNs) to create precise intended sequence modifications, including single nucleotide substitutions. Finally, we describe and validate simple strategies that improve the targeting range of RGNs from 1 in every 128 basepairs (bps) of random DNA sequence to 1 in every 8 bps. Together, these advances expand the utility of the CRISPR-Cas system in the zebrafish beyond somatic indel formation to heritable and precise genome modifications.


Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?
There is increasing evidence that pregnancy alters the function of drug-metabolizing enzymes and drug transporters in a gestational-stage and tissue-specific manner. In vivo probe studies have shown that the activity of several hepatic cytochrome P450 enzymes, such as CYP2D6 and CYP3A4, is increased during pregnancy, whereas the activity of others, such as CYP1A2, is decreased. The activity of some renal transporters, including organic cation transporter and P-glycoprotein, also appears to be increased during pregnancy. Although much has been learned, significant gaps still exist in our understanding of the spectrum of drug metabolism and transport genes affected, gestational age-dependent changes in the activity of encoded drug metabolizing and transporting processes, and the mechanisms of pregnancy-induced alterations. In this issue of Drug Metabolism and Disposition, a series of articles is presented that address the predictability, mechanisms, and magnitude of changes in drug metabolism and transport processes during pregnancy. The articles highlight state-of-the-art approaches to studying mechanisms of changes in drug disposition during pregnancy, and illustrate the use and integration of data from in vitro models, animal studies, and human clinical studies. The findings presented show the complex inter-relationships between multiple regulators of drug metabolism and transport genes, such as estrogens, progesterone, and growth hormone, and their effects on enzyme and transporter expression in different tissues. The studies provide the impetus for a mechanism- and evidence-based approach to optimally managing drug therapies during pregnancy and improving treatment outcomes.


Prevalence and drug resistance characteristics of carbapenem-resistant Enterobacteriaceae in Hangzhou, China.
With the abuse of antimicrobial agents in developing countries, increasing number of carbapenem-resistant Enterobacteriaceae (CRE) attracted considerable public concern. A retrospective study was conducted based on 242 CRE strains from a tertiary hospital in Hangzhou, China to investigate prevalence and drug resistance characteristics of CRE in southeast China. Bacterial species were identified. Antimicrobial susceptibility was examined by broth microdilution method or epsilometer test. Resistant β-lactamase genes were identified by polymerase chain reaction and sequencing. Genotypes were investigated by phylogenetic analysis. Klebsiella pneumoniae and Escherichia coli were the most prevalent types of species, with occurrence in 71.9% and 21.9% of the strains, respectively. All strains exhibited high resistance (> 70%) against β-lactam antibiotics, ciprofloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin but exhibited low resistance against tigecycline (0.8%) and minocycline (8.3%). A total of 123 strains harbored more than two kinds of β-lactamase genes. blaKPC-2, blaSHV-11, blaTEM-1, and blaCTX-M-14 were the predominant genotypes, with detection rates of 60.3%, 61.6%, 43.4%, and 16.5%, respectively, and were highly identical with reference sequences in different countries, indicating potential horizontal dissemination. IMP-4 was the most frequent class B metallo-lactamases in this study. In conclusion, continuous surveillance and effective prevention should be emphasized to reduce spread of CRE.


Control of the actinomycin biosynthetic pathway in and actinomycin resistance of Streptomyces spp.
Using actinomycin-producing and nonproducing strains of Streptomyces antibioticus, I studied several steps in the biosynthetic pathway of this antibiotic. Actinomycin-nonproducing strains derived after acriflavine or novobiocin treatment showed activity of kynurenine formamidase and phenoxazinone synthase as high as that of the parental strain, but these nonproducing strains failed to convert 4-methyl-3-hydroxy-anthranilic acid to actinomycin. In addition, accumulation of 4-methyl-3-hydroxyanthranilic acid (in the presence of D-valine) was not detected in the nonproducing isolates. Actinomycin-nonproducing strains derived after acriflavine treatment of Streptomyces parvulus showed a drastic decrease of resistance to the antibiotic. However these strains regained resistance after preincubation with a small amount of actinomycin D.


Transcriptional profiling of Pseudomonas aeruginosa PAO1 in response to anti-biofilm and anti-infection agent exopolysaccharide EPS273.
Relatively, few anti-biofilm polysaccharides against Pseudomonas aeruginosa were done to investigate the underlying molecular mechanism. Exopolysaccharide EPS273 can clearly reduce biofilm formation and infection of P. aeruginosa. This study aims to investigate its anti-biofilm and anti-infection mechanism on transcriptional level. Herein, we used an RNA-Seq transcriptomic approach to investigate the underlying anti-biofilm and anti-infection mechanism of EPS273. The expression levels of a large number of genes were changed after P. aeruginosa PAO1 was treated with EPS273. Especially, the genes related to biofilm formation, such as gene involved in production of extracellular matrix and virulence factor, genes involved in flagella and cell motility and genes involved in iron acquisition. Notably, the expression levels of genes involved in regulatory and signal transduction were markedly downregulated, such as two-component system PhoP-PhoQ and quorum sensing (QS) system LasI/LasR and RhlI/RhlR. Furthermore, when genes phoP and phoQ were disrupted, respectively, the reduction of biofilm formation and cell motility in mutant △phoP or △phoQ was also detected. EPS273 may exert its anti-biofilm and anti-infection function by downregulating gene expression of two-component system PhoP-PhoQ and QS systems LasI/LasR and RhlI/RhlR of P. aeruginosa, which further regulated expression of genes involved in biofilm formation. Our data will expand understanding of anti-biofilm mechanisms of polysaccharides on transcriptomic level.


Thrombin-induced chemokine production in endometrial stromal cells.
In order to investigate the regulation of chemokines [interleukin-8 (IL-8), growth-regulated oncogene (GRO)α, monocyte chemoattractant protein-1 (MCP-1)) induced by thrombin in endometrial stromal cells (ESCs), the effects of thrombin, a protease activated receptor (PAR)-1 antagonist (PPACK), mitogen-activated protein kinase kinase inhibitor (U0126), phospholipase C inhibitor (U-73122), an antagonist of the intracellular InsP3 receptor (2-aminoethoxy-diphenylborate (2-APB)] and a protein kinase C inhibitor (GF-109203X) on the production of chemokines by ESCs were evaluated. ESCs from eight endometrial specimens in the secretory phase were cultured and incubated for 24h with thrombin and PPACK, U0126, U-73122, 2-APB or GF-109203X. The levels of IL-8, GROα and MCP-1 in the culture medium were measured by means of ELISA. The activation of MAP kinase was detected by western blot analysis using anti-phosphorylated MAP kinase (ERK1/2) antibody. Following stimulation by thrombin, the production of IL-8, GROα and MCP-1 increased significantly in a dose-dependent manner. PPACK, U0126, U-73122, 2-APB or GF-109203X suppressed the increases in production of IL-8, GROα and MCP-1 induced by thrombin (P < 0.001, P <0.001 and P <0.001, respectively). MAP kinase activities were induced by treatment with thrombin, and were suppressed by PPACK, U0126, U-73122, 2-APB or GF-109203X. Our results suggest that thrombin stimulates the production of IL-8, GROα and MCP-1 via PAR-1 by a mechanism involving the MAP kinase system. The increases in IL-8, GROα and MCP-1 may contribute to the maintenance of implantation involving leukocyte chemotaxis.


Detection of oligomers and fibrils of α-synuclein by AIEgen with strong fluorescence.
We report a fluorophore, TPE-TPP, with AIE characteristics which is utilized as a fluorescence probe to monitor the α-synuclein (α-Syn) fibrillation process. Compared with ThT, TPE-TPP shows a higher sensitivity in the detection of α-Syn oligomers as well as fibrils with a stronger fluorescence. The performance of TPE-TPP was evaluated using fluorescence, AFM, dot blot, and SEC.


Producing benchmarks for clinical practice.
Clinical benchmarking has huge potential for improving health care. Students exploring benchmarks for fundamental and essential aspects of care produced a number of interesting key factors and continuums of care. A significant feature of the development of the Department of Health benchmarks has been the inclusion of service users.


[Cyclic strain promotes migration of human periodontal ligament cell via extracellular signal-regulated kinase (ERK) signaling pathway].
To study the effect of cyclic strain on migration of human periodontal ligament cell(hPDLC) and underlying mechanism. The cultured hPDLC were subjected to 10% or 20%-elongation magnitude cyclic strain at frequency of 0.1 Hz by FX-4000T system for 6 or 24 hours-duration respectively, while the static group serves as control. hPDLC migration was assayed by wound healing method. The expressions of matrix metalloproteinases-9 (MMP-9) and p-ERK1/2 in hPDLC without or with cyclic strain were analyzed by Western blotting. To investigate the effect of ERK signaling pathway and MMP-9 on migration of hPDLC, the cells were incubated with PD98059, a specific extracellular signal-regulated kinase (ERK) kinase inhibitor, or doxycycline, a MMP inhibitor. Then the expressions of p-ERK1/2 and MMP-9 and hPDLC migration were analyzed. In wound healing tests, the migration of hPDLC exposed to 10% or 20%-cyclic strain at 0.1 Hz-frequency for 6 hours was not apparent but became significantly different for 24 hours (P < 0.05) compared to control. Furthermore, the 20%-elongation magnitude of cyclic strain had more remarkable effect on migration of hPDLC than 10%-elongation magnitude at 24 hours-duration (P < 0.05). Cyclic strain obviously increased the expression of MMP-9 in hPDLC (P < 0.05). PD98059 could repress not only the activation of p-ERK1/2 but also the expression of MMP-9 induced by cyclic strain in hPDLC. The migration of hPDLC enhanced by cyclic strain was repressed by DOX or PD98059 in wound healing tests. Cyclic strain promotes the migration of hPDLC through activating ERK signaling pathway and inducing the expression of MMP-9.


Limits in motor control bandwidth during stick balancing.
Why can we balance a yardstick but not a pencil on the tip of our finger? As with other physical systems, human motor control has constraints, referred to as bandwidth, which restricts the range of frequency over which the system can operate within some tolerated level of error. To investigate control bandwidth, the natural frequency of a stick used during a stick-balancing task was modified by adjusting the height of a mass attached to the stick. The ability to successfully balance the stick with the mass positioned at four different heights was determined. In addition, electromyographic signals from forearm and trunk muscles were recorded during the trials. We hypothesized that 1) the probability of successfully balancing would decrease as mass height decreased; and 2) the level of muscle activation in both agonist and antagonist would increase as the natural frequency of the stick increased. Results showed that as the mass height decreased the probability of successfully balancing the stick decreased. Changes in the probability of success with respect to mass height showed a threshold effect, suggesting that limits in human control bandwidth were approached at the lowest mass height. Also, the level of muscle activation in both the agonist and antagonist of the forearm and trunk increased linearly as the natural frequency of the stick increased. These changes in muscle activation suggest that the central nervous system adapts muscle activation to task dynamics, possibly to improve control bandwidth.


Putting Everything in Context.
In response to Casasanto, Brookshire, and Ivry (2015), we address four points: First, we engaged in conceptual replications of Brookshire, Casasanto, and Ivry (2010), not direct replications. Second, we did not question the validity of Brookshire et al.'s (2010) results, nor the similar findings of other researchers, but instead explained divergent findings within an integrated theoretical framework. Third, challenges to the construct of automaticity, including ours, were widespread, long before Brookshire et al.'s (2010) article. Fourth, the planned comparisons that we reported tested our theoretical claims and offered strong evidence for them.


Sound segregation via embedded repetition is robust to inattention.
The segregation of sound sources from the mixture of sounds that enters the ear is a core capacity of human hearing, but the extent to which this process is dependent on attention remains unclear. This study investigated the effect of attention on the ability to segregate sounds via repetition. We utilized a dual task design in which stimuli to be segregated were presented along with stimuli for a "decoy" task that required continuous monitoring. The task to assess segregation presented a target sound 10 times in a row, each time concurrent with a different distractor sound. McDermott, Wrobleski, and Oxenham (2011) demonstrated that repetition causes the target sound to be segregated from the distractors. Segregation was queried by asking listeners whether a subsequent probe sound was identical to the target. A control task presented similar stimuli but probed discrimination without engaging segregation processes. We present results from 3 different decoy tasks: a visual multiple object tracking task, a rapid serial visual presentation (RSVP) digit encoding task, and a demanding auditory monitoring task. Load was manipulated by using high- and low-demand versions of each decoy task. The data provide converging evidence of a small effect of attention that is nonspecific, in that it affected the segregation and control tasks to a similar extent. In all cases, segregation performance remained high despite the presence of a concurrent, objectively demanding decoy task. The results suggest that repetition-based segregation is robust to inattention.


Study of early leaf senescence in Arabidopsis thaliana by quantitative proteomics using reciprocal 14N/15N labeling and difference gel electrophoresis.
Leaf senescence represents the final stage of leaf development and is associated with fundamental changes on the level of the proteome. For the quantitative analysis of changes in protein abundance related to early leaf senescence, we designed an elaborate double and reverse labeling strategy simultaneously employing fluorescent two-dimensional DIGE as well as metabolic (15)N labeling followed by MS. Reciprocal (14)N/(15)N labeling of entire Arabidopsis thaliana plants showed that full incorporation of (15)N into the proteins of the plant did not cause any adverse effects on development and protein expression. A direct comparison of DIGE and (15)N labeling combined with MS showed that results obtained by both quantification methods correlated well for proteins showing low to moderate regulation factors. Nano HPLC/ESI-MS/MS analysis of 21 protein spots that consistently exhibited abundance differences in nine biological replicates based on both DIGE and MS resulted in the identification of 13 distinct proteins and protein subunits that showed significant regulation in Arabidopsis mutant plants displaying advanced leaf senescence. Ribulose 1,5-bisphosphate carboxylase/oxygenase large and three of its four small subunits were found to be down-regulated, which reflects the degradation of the photosynthetic machinery during leaf senescence. Among the proteins showing higher abundance in mutant plants were several members of the glutathione S-transferase family class phi and quinone reductase. Up-regulation of these proteins fits well into the context of leaf senescence since they are generally involved in the protection of plant cells against reactive oxygen species which are increasingly generated by lipid degradation during leaf senescence. With the exception of one glutathione S-transferase isoform, none of these proteins has been linked to leaf senescence before.


Patients' perceptions of their physician's role in smoking cessation by age and readiness to stop smoking.
Patients' perceptions of their physician's role in smoking cessation, using the 4As protocol (asking, advising, assisting, and arranging), were assessed with a focus on associations with age (18-29, 30-49, and > or = 50) and stage of readiness to stop smoking (precontemplation, contemplation, and preparation). Self-administered questionnaires were completed by 524 smokers presenting for regularly scheduled appointments at six clinics of an HMO in the Chicago metropolitan area. Almost all patients said their physician should ask about their smoking status and advise them to quit. About half said their physician should assist them with quitting, and about two-thirds said their physician should follow up (arrange) on their smoking behavior. Bivariate associations were found for endorsement of the 4As with both age and stage. Multiple logistic regressions found age was the most consistent and strongest correlate of 4As endorsement, with younger smokers more likely than those age 50 or older to endorse the 4As protocol. A proactive health promotion orientation should be encouraged among physicians. Patients should be screened for stage of readiness to stop smoking so that health-care providers can emphasize aspects of the 4As protocol that are most appropriate for each patient. Age-tailored smoking cessation strategies should be employed within stages of readiness to stop smoking.


Toxoplasmosis accelerates acquisition of epilepsy in rats undergoing chemical kindling.
Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One-third of the world population has been infected with Toxoplasma gondii. This intracellular parasite has high tropism for excitable cells including neurons. We assessed impact of acute and chronic T. gondii infection on epileptogenesis in pentylenetetrazole (PTZ) kindling model in male rats. T. gondii cysts were administered to rats by intraperitoneal (i.p.) injection. The presence of T. gondii cysts in the brain of rats was verified by hematoxylin-eosin staining. One and eight weeks after cysts injection, as acute and chronic phases of infection, PTZ (30mg/kg, i.p.) was injected to the rats every other day until manifestation of generalized seizures. Histologic findings confirmed cerebral toxoplasmosis in rats. The rats with acute or chronic Toxoplasma infection became kindled by lower number of PTZ injections (14.8±1 and 13.6±1 injections, respectively) compared to corresponding uninfected rats (18.7±1 and 16.9±1 injections, p<0.05). Toxoplasma infection increased the rate of kindling in rats. The chronically-infected rats achieved focal and also generalized seizures earlier than the rats with acute infection. Toxoplasmosis might be considered as a risk factor for acquisition of epilepsy.


Evaluation of the Panbio dengue virus nonstructural 1 antigen detection and immunoglobulin M antibody enzyme-linked immunosorbent assays for the diagnosis of acute dengue infections in Laos.
We evaluated 2 commercial enzyme-linked immunosorbent assays (ELISAs) for the diagnosis of dengue infection; one a serologic test for immunoglobulin M (IgM) antibodies, the other based on detection of dengue virus nonstructural 1 (NS1) antigen. Using gold standard reference serology on paired sera, 41% (38/92 patients) were dengue confirmed, with 4 (11%) acute primary and 33 (87%) acute secondary infections (1 was of indeterminate status). Sensitivity of the NS1-ELISA was 63% (95% confidence interval [CI], 53-73) on admission samples but was much less sensitive (5%; 95% CI, 1-10) on convalescent samples. The IgM capture ELISA had a lower but statistically equivalent sensitivity compared with the NS1-ELISA for admission samples (45%; 95% CI, 35-55) but was more sensitive on convalescent samples (58%; 95% CI, 48-68). The results of the NS1 and IgM capture ELISAs were combined using a logical OR operator, increasing the sensitivity for admission samples (79%; 95% CI, 71-87), convalescent samples (63%; 95% CI, 53-73), and all samples (71%; 95% CI, 65-78).


Optic Neuritis in the Older Chinese Population: A 5-Year Follow-Up Study.
This study aims to describe the clinical manifestations and outcomes in a cohort of older Chinese patients. A retrospective study of patients aged ≥ 45 years who had a first episode of optic neuritis (ON) between May 2008 and November 2012. Clinical features at onset and last follow-up were analyzed within subgroups (age 45-65 years and age ≥ 65 years). 76 patients (99 eyes) were included, of which 58% were females. The mean age at presentation was 55.53 ± 8.29 years (range: 45-83 years). Vision loss was severe at presentation, with initial best corrected vision activity (BCVA) < 20/200 in 93% and final BCVA < 20/200 in 53% of patients at 5-year follow-up. Final BCVA significantly correlated with the initial BCVA and peripapillary retinal nerve fiber layer. At last follow-up, 14.5% were diagnosed with neuromyelitis optica spectrum disorder (NMOSD), 1.3% were diagnosed with multiple sclerosis (MS), 5.2% with chronic relapsing inflammatory optic neuropathy, 1.3% with infectious ON, and 19.7% with autoimmune ON. None of the elderly group (≥65 years) developed NMOSD or MS. Chinese patients in the age group ≥ 65 years with ON are less likely to develop NMOSD or MS. Notwithstanding, they had more severe visual loss at onset and poor recovery.


Generation of site-distinct N-glycan variants for in vitro bioactivity testing.
Glycosylation, a critical product quality attribute, may affect the efficacy and safety of therapeutic proteins in vivo. Chinese hamster ovary fed-batch cell culture batches yielded consistent glycoprofiles of a Fc-fusion antibody comprizing three different N-glycosylation sites. By adding media supplements at specific concentrations in cell culture and applying enzymatic glycoengineering, a diverse N-glycan variant population was generated, including high mannose, afucosylated, fucosylated, agalactosylated, galactosylated, asialylated, and sialylated forms. Site-specific glycosylation profiles were elucidated by glycopeptide mapping and the effect of the glycosylation variants on the FcγRIIIa receptor binding affinity and the biological activity (cell-based and surface plasmon resonance) was assessed. The two fusion body glycosylation sites were characterized by a high degree of sialic acid, more complex N-glycan structures, a higher degree of antennarity, and a site-specific behavior in the presence of a media supplement. On the other hand, the media supplements affected the Fc-site glycosylation heterogeneity similarly to the various studies described in the literature with classical monoclonal antibodies. Enzymatic glycoengineering solely managed to generate high levels of galactosylation at the fusion body sites. Variants with low core fucosylation, and to a lower extent, high mannose glycans exhibited increased FcγRIIIa receptor binding affinity. All N-glycan variants exhibited weak effects on the biological activity of the fusion body. Both media supplementation and enzymatic glycoengineering are suitable to generate sufficient diversity to assess the effect of glycostructures on the biological activity.


Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy.
Overexpression of ErbB-2/HER2 is associated with aggressive human malignancies, and therapeutic strategies targeting the oncoprotein are currently in different stages of clinical application. Tyrosine kinase inhibitors (TKIs) that block the nucleotide-binding site of the kinase are especially effective against tumors. Here we report an unexpected activity of TKIs: along with inhibition of tyrosine phosphorylation, they enhance ubiquitylation and accelerate endocytosis and subsequent intracellular destruction of ErbB-2 molecules. Especially potent is an irreversible TKI (CI-1033) that alkylates a cysteine specific to ErbB receptors. The degradative pathway stimulated by TKIs appears to be chaperone mediated, and is common to the heat shock protein 90 (Hsp90) antagonist geldanamycin and a stress-induced mechanism. In agreement with this conclusion, CI-1033 and geldanamycin additively inhibit tumor cell growth. Based upon a model for drug-induced degradation of ErbB-2, we propose a general strategy for selective destruction of oncoproteins by targeting their interaction with molecular chaperones.


[Chronobiological evaluation of effects biomarkers and sampling].
Occupational exposure to oxidants is often associated with an increase in the levels of oxidative DNA damage in urine. Besides 8-hydroxy-2'-deoxyguanosine (8-oxo-dG), other products of position-8 guanine oxidation have been identified in urine, including 8-hydroxy-guanine (8-oxo-G) and 8-hydroxyguanosine (8-oxy-Guo). The aim of the present study was the characterization of these effect biomarkers in terms of inter- and intra-individuals varaibility, as well as in terms of their excretion profile during a 24 h-period. Urine samples were collected from 11 volunteers (6 samples/day). Urine concentrations of 8-oxo-G, 8-oxo-Guo, and 8-oxo-dG were determined by liquid chromatography-tandem mass spectrometry. The inter-individual variability, expressed as variation coefficient, was 85-150% for 8-oxo-G, 20-45% for 8-oxo-Guo, and 30-45% for 8-oxo-dG. The statistical anaysis for repeated measurements showed that none of the biomarkers was affected by significant variation during the day (one-way ANOVA, p < 0.05), thus excluding the existence of a circadian rhythm. We conclude that the sampling time is not critical for the assessment of oxidative DNA damage in urine.


Relative position and extent of the nasal and orbital openings in Gorilla, Pan and the human species from the study of their areas and centres of area.
In order to quantify the relative position and extent of the nasal and orbital openings in hominoid primates, a new methodology based on image analysis was developed and applied to a series of 134 hominoid skulls (52 Gorilla gorilla; 30 Pan troglodytes; 44 Homo sapiens, and, as comparison material, 8 Pongo pygmaeus). The areas and the centres of area of the orbital and nasal openings were determined automatically. The orbitonasal triangle connecting these three centres of area was then constructed. This triangle was used to quantify the elongation of the face. It was most elongated in gorilla, shortest in the human species and intermediate in Pan; the elongation in Pongo was close to that in Gorilla. The proportions of the areas of the orbital and nasal openings in the face were related to the extent of the bony structures of the midface and were thus used to quantify the facial robustness. A robust face was demonstrated in Gorilla, but a gracile face in the human species. Robusticity in Pan was intermediate.


Perspectives on Violence Against Women: A Study of United States Nursing Textbooks.
This study examines conceptualizations of violence against women in U.S. nursing textbooks published from 1995 to 2005. Framing this pivotal decade, the federal Violence Against Women Act (VAWA) was passed and renewed. The American Nurses Association, the National League for Nursing, and the American Association of Colleges of Nursing also recognized violence against women as a health care priority. Sampling 107 generalist nursing textbooks from 1995 to 2005, the current study analyzes textbook terminologies, arguments, and protocols. Textbooks including violence were empirically tested for their application of gender neutral, symmetrical, and asymmetrical theoretical frameworks. Over 40% of generalist textbooks did not mention violence against women. Despite the VAWA in 1994 and broad recognition across national nursing organizations, textbooks did not change with regard to their treatment of violence over the next decade. The frameworks that nursing textbooks use may foster challenges for nurses in recognizing, supporting, and assisting women who are victims/survivors of violence. [J Nurs Educ. 2017;56(3):164-169.].


Validation of the sensitivity of the National Emergency X-Radiography Utilization Study (NEXUS) Head computed tomographic (CT) decision instrument for selective imaging of blunt head injury patients: An observational study.
Clinicians, afraid of missing intracranial injuries, liberally obtain computed tomographic (CT) head imaging in blunt trauma patients. Prior work suggests that clinical criteria (National Emergency X-Radiography Utilization Study [NEXUS] Head CT decision instrument [DI]) can reliably identify patients with important injuries, while excluding injury, and the need for imaging in many patients. Validating this DI requires confirmation of the hypothesis that the lower 95% confidence limit for its sensitivity in detecting serious injury exceeds 99.0%. A secondary goal of the study was to complete an independent validation and comparison of the Canadian and NEXUS Head CT rules among the subgroup of patients meeting the inclusion and exclusion criteria. We conducted a prospective observational study of the NEXUS Head CT DI in 4 hospital emergency departments between April 2006 and December 2015. Implementation of the rule requires that patients satisfy 8 criteria to achieve "low-risk" classification. Patients are excluded from "low-risk" classification and assigned "high-risk" status if they fail to meet 1 or more criteria. We examined the instrument's performance in assigning "high-risk" status to patients requiring neurosurgical intervention among a cohort of 11,770 blunt head injury patients. The NEXUS Head CT DI assigned high-risk status to 420 of 420 patients requiring neurosurgical intervention (sensitivity, 100.0% [95% confidence interval [CI]: 99.1%-100.0%]). The instrument assigned low-risk status to 2,823 of 11,350 patients who did not require neurosurgical intervention (specificity, 24.9% [95% CI: 24.1%-25.7%]). None of the 2,823 low-risk patients required neurosurgical intervention (negative predictive value [NPV], 100.0% [95% CI: 99.9%-100.0%]). The DI assigned high-risk status to 759 of 767 patients with significant intracranial injuries (sensitivity, 99.0% [95% CI: 98.0%-99.6%]). The instrument assigned low-risk status to 2,815 of 11,003 patients who did not have significant injuries (specificity, 25.6% [95% CI: 24.8%-26.4%]). Significant injuries were absent in 2,815 of the 2,823 patients assigned low-risk status (NPV, 99.7% [95% CI: 99.4%-99.9%]). Of our patients, 7,759 (65.9%) met the inclusion and exclusion criteria of the Canadian Head CT rule, including 111 patients (1.43%) who required neurosurgical intervention and 306 (3.94%) who had significant intracranial injuries. In our study, the Canadian criteria for neurosurgical intervention identified 108 of 111 patients requiring neurosurgical intervention to yield a sensitivity of 97.3% (95% CI: 92.3%-99.4%) and exhibited a specificity of 58.8% (95% CI: 57.7%-59.9%). The NEXUS rule, when applied to this same cohort, identified all 111 patients requiring neurosurgical intervention, yielding a sensitivity of 100% (95% CI: 96.7%-100.0%) with a specificity of 32.6% (95% CI: 31.5%-33.6%). Our study found that the Canadian medium-risk factors identified 301 of 306 patients with significant injuries (sensitivity = 98.4%; 95% CI: 96.2%-99.5%), while the NEXUS rule identified 299 of these patients (sensitivity = 97.7%; 95% CI: 95.3%-99.1%). In our study, the Canadian medium-risk rule exhibited a specificity of 12.3% (95% CI: 11.6%-13.1%), while the NEXUS rule exhibited a specificity of 33.3% (95% CI: 32.3%-34.4%). Limitations of the study may arise from application of the rule by different clinicians in different environments. Clinicians may vary in their interpretation and application of the instrument's criteria and risk assignment and may also vary in deciding which patients require intervention. The instrument's specificity is also subject to spectrum bias and may change with variations in the proportion of "low-risk" patients seen in other centers. The NEXUS Head CT DI reliably identifies blunt trauma patients who require head CT imaging and could significantly reduce the use of CT imaging.


[Mechanisms of hepatic fibrogenesis].
Hepatic fibrosis is a scaring process leading to cirrhosis, a major complication of numerous chronic liver diseases. Hepatic stellate cells play a central role in the fibrotic process. After parenchymal or biliary injury, cytokines and growth factors allow the recruitment, proliferation, and activation, of stellate cells toward myofibroblasts, which secrete the extracellular matrix. Fibrosis, resulting from the failure of the balance between synthesis and degradation of extracellular matrix, is an evolutive and potentially reversible process. Histological examination is the main investigation to quantify fibrosis. Serological tests are warranted to allow a non invasive follow up of patients. Development of antifibrotic therapies should soon permit to slow down the evolution toward cirrhosis, limiting the needs for hepatic transplantation.


Herpes (Shalbeket) in judaic sources: a synopsis of a book in preparation.
It is generally accepted that the earliest reference to Herpes is that of the Greek historian Herodotus and was used as a description of various "creeping skin diseases"--approx. 2000 years ago. Herpes, known in Hebrew as Shalbeket (boil, vesicle) is mentioned in the Book of Exodus as early as about 3500 years ago. This is a significant revelation in medical history that the earliest reference to Herpes (shalbeket) was mentioned 3500 years ago as Shalbukin (vesicles) in conjunction with Shekhin. These names, "boils," "creeping" are two descriptions of the external signs of Herpes; indicative of the ability of the ancients to identify diseases by their external appearances and to deal with their medical and sociological aspects.


Simultaneous determination of rufloxacin and furprofen in plasma by derivative UV-spectrophotometry.
A procedure for the simultaneous determination of rufloxacin and furprofen in rat plasma by second-derivative UV-spectrophotometry is described. The proposed method, which gives useful data for pharmacokinetic studies, is simple and rapid, and allows precise and accurate results.


Can Lighting Influence Self-Disclosure?
With the advent of social networks where people disclose a lot of their information and opinions publicly, this research attempted to re-look at the effect of environmental lighting on willingness and actual disclosure of personal information. Previous literatures mostly addressed counseling setups and the findings were mixed. In order to clarify the effect of lighting on self-disclosure, two experiments were conducted with reported willingness to disclose (Experiment 1) as well as actual disclosure (Experiment 2) on a range of topics like social issues, body, money, work, and personality. While quite a handful of studies have reported differences in disclosure from very subtle environmental lighting manipulations, in both experiments we could not find any effect of ambient room lighting conditions on self-disclosure. These results call for caution both in over-interpreting subtle environmental effects and in increased generalization of perceptual metaphors to actual behavior.


Urinary iodine excretion in pregnant women as an index of the impact of a national iodization programme.
To evaluate the extent to which increase in iodine requirement was achieved in pregnant women who attended the antenatal clinic at Harare Central Hospital. Cross sectional. Samples were collected from pregnant women attending antenatal clinic at Harare Central Hospital, and from lactating mothers and their infants. 100 pregnant women attending the antenatal clinic at Harare Central hospital, 80 infants, 80 lactating women and 18 non-pregnant women. Comparison of urinary iodine excretion levels among pregnant women, lactating mothers and their infants. The results indicated lower urinary iodine excretion levels for the pregnant women and lactating mothers compared to the urinary iodine excretion of the infants and the breast milk iodine content. The urinary iodine excretion level of the non-pregnant control women was median (first and third quartiles): 18.5 microg/dl (30.0, 30.2 microg/dl). The urinary iodine excretion level of the lactating mothers was median (first and third quartiles): 12.0 mg/dl (7.6, 19.5 mg/dl) compared to the level of the infants, median (first and third quartiles): 26.5 mg/dl (18.8, 11.5 mg/dl). A significant difference was noted between the median urinary iodine excretion levels of the mothers, and the median levels of the infants, p = 0.001. The mean milk iodine content was 21.2 +/- 6.8 mg/dl. There was no correlation between breast milk iodine levels and the urinary iodine excretion levels of the infants, (p = 0.96, r = 0.006). Positive correlation was found between maternal urinary iodine excretion levels and the urinary iodine excretion levels of the infants, p = 0.016 r = 0.285. Serum FT4, and TSH levels were found to be higher for infants at six weeks after birth, (FT4 =20.91 +/- 5.65 pmol/L) and median TSH = 2.28 mIU/ml (1.36, 0.86) mIU/rnl, compared to levels at 12 weeks postpartum: (FT4 = 17.53-*6.4 pmol/L) and median TSH = 2.02 mIU/ml, (0.84, 1.55) mIU/ml. The differences were not significant. The results indicated a significant reduction in the urinary iodine content of pregnant women, and lactating mothers which did not appear to have any relationship to the urinary iodine excretion levels of infants and iodine content of breast milk. Iodine intake needed to be raised to reflect the recent proposed recommendations.


An OTU deubiquitinating enzyme in Eimeria tenella interacts with Eimeria tenella virus RDRP.
Chicken coccidiosis, a disease caused by seven species of Eimeria (Apicomplexa: Coccidia), inflicts severe economic losses on the poultry industry. Eimeria tenella is the one of the most virulent species pathogenic to chickens. Many parasitic protozoans are parasitised by double-stranded (ds) RNA viruses, and the influence of protozoan viruses on parasitic protozoans has been extensively reported. E. tenella RNA virus 1 (Etv) was identified in E. tenella, and the complete genome sequence of Etv was analysed. Here, we screened Etv-RNA-dependent RNA polymerase (RDRP)-interacting host protein E. tenella ovarian tumour (OTU) protein-like cysteine protease (Et-OTU) using a yeast two-hybrid system with pGBKT7-RDRP plasmid serving as bait. A previous study demonstrated that Et-OTU could regulate the telomerase activity of E. tenella, indicating that Et-OTU affects E. tenella proliferation. However, whether Etv-RDRP affects the molecular biological characteristics of E. tenella by interacting with OTU remains unclear. We obtained seven positive clones from the initial screen, and six of the seven preys were identified as false-positives. Finally, we identified an RDRP-associated protein predicted to be an E. tenella OTU protein. A α-galactosidase assay showed that the bait vector did not activate the GAL4 reporter gene, indicating no autoactivation activity from the RDRP bait fusion. Pull-down and co-immunoprecipitation assays verified the interaction between Et-OTU and Etv-RDRP both intracellularly and extracellularly. Additionally, Et-OTU was able to deconjugate K48- and K6-linked di-ubiquitin (di-Ub) chains in vitro but not K63-, K11-, K29-, or K33-linked di-Ub chains. The C239A and H351A mutations eliminated the deubiquitinase (DUB) activity of Et-OTU, whereas the D236A mutation did not. Additionally, when combined with RDRP, the DUB activity of Et-OTU towards K48- and K6-linked chains was significantly enhanced. Etv-RDRP interacts with Et-OTU both intracellularly and extracellularly. Etv-RDRP enhances the hydrolysis of Et-OTU to K6- or K48-linked ubiquitin chains. This study lays the foundation for further research on the relationship between E. tenella and Etv.


Medical students' experiences with addicted patients: a web-based survey.
Project CREATE was an initiative to strengthen undergraduate medical education in addictions. As part of a needs assessment, forty-six medical students at Ontario's five medical schools completed a bi-weekly, interactive web-based survey about addiction-related learning events. In all, 704 unique events were recorded, for an average of 16.7 entries per student. The most commonly discussed topic was alcohol withdrawal and the complications of alcohol use. The most common learning venues were lectures and clinical encounters in the emergency department or hospital. The proportion of advice-related topics (e.g., advice to drinkers and smokers) to advice plus non-advice related topics (e.g., medical complications) was greater for outpatient and community settings than for acute care and didactic settings (ratio 1.29, chi sq 15.85, p < 0.01). Students reacted strongly to the psychosocial impact of addictions on patients, yet they viewed addiction as a personal choice, not an illness. Medical students are not being trained to diagnose addiction or provide advice and counseling. Medical schools need to provide students with positive clinical experiences supervised by physicians experienced in addictions.


Integrated Venomics and Venom Gland Transcriptome Analysis of Juvenile and Adult Mexican Rattlesnakes Crotalus simus, C. tzabcan, and C. culminatus Revealed miRNA-modulated Ontogenetic Shifts.
Adult rattlesnakes within genus Crotalus express one of two distinct venom phenotypes, type I (hemorrhagic) and type II (neurotoxic). In Costa Rican Central American rattlesnake, ontogenetic changes in the concentration of miRNAs modulate venom type II to type I transition. Venomics and venom gland transcriptome analyses showed that adult C. simus and C. tzabcan expressed intermediate patterns between type II and type I venoms, whereas C. culminatus had a canonical type I venom. Neonate/juvenile and adult Mexican rattlesnakes showed notable inter- and intraspecific variability in the number, type, abundance and ontogenetic shifts of the transcriptional and translational venom gland activities. These results support a role for miRNAs in the ontogenetic venom compositional changes in the three congeneric Mexican rattlesnakes. It is worth noting the finding of dual-action miRNAs, which silence the translation of neurotoxic heterodimeric PLA2 crotoxin and acidic PLA2 mRNAs while simultaneously up-regulating SVMP-targeting mRNAs. Dual transcriptional regulation potentially explains the existence of mutually exclusive crotoxin-rich (type-II) and SVMP-rich (type-I) venom phenotypic dichotomy among rattlesnakes. Our results support the hypothesis that alterations of the distribution of miRNAs, modulating the translational activity of venom gland toxin-encoding mRNAs in response to an external cue, may contribute to the mechanism generating adaptive venom variability.


Extended sleeve lobectomy for interlobar lymph node metastasis invading the bronchus from peripheral lung cancer.
Although extended sleeve lobectomy has been used as an alternative to pneumonectomy for the treatment of centrally located lung cancer, the validity of this surgical procedure is unclear in patients with peripheral lung cancer with interlobar lymph node metastasis invading the bronchus. We herein report four patients with peripheral lung cancer in the left lower lobe who underwent extended sleeve lobectomy consequent to interlobar lymph node metastasis. The tumor and metastasized lymph node was extirpated en bloc with division of the main bronchus and upper division bronchus, and those bronchi were anastomosed using the telescope method. All patients were doing well without recurrence. Extended sleeve lobectomy may be applicable to patients with peripheral lung cancer with interlobar lymph node metastasis invading the bronchus to avoid pneumonectomy.


Pediatric robotic pyeloplasties: initial experience at a single center.
The purpose of this analysis was to review our initial experience of pediatric robotic-assisted pyeloplasties (RALPs). Our case series spanned a 7-year period (January 2004-February 2011). The initial 20 cases were reviewed retrospectively (RG group), and the later 20 cases were seen prospectively (PG group). We compared outcomes between these two groups. After institutional review board approval, all charts were reviewed, and outcomes were based on postoperative imaging. For continuous variables t tests were performed, and for categorical variables Fisher's exact tests were performed. Statistical analysis was performed with SPSS version 17.0 software (SPSS, Inc., Chicago, IL). There was no significant difference in demographics between the two groups. Median age at time of surgery was 64 months (PG) and 36 months (RG). Narcotic use was statistically similar among the groups when comparing median morphine intravenous equivalent per kilgram. Mean follow-up was 15.6 months (PG) and 41.8 months (RG). Postoperative imaging was stable or improved in 95% (PG) and 100% (RG). RALP in 1 patient in the PG group failed and later required repeat surgery (5%). The only identified significant difference between the two groups was surgical time. Mean operative time was reduced by over an hour between the two time periods (230 minutes for PG, 297 minutes for RG [P<.01]). The experience in pediatric RALP is growing at our institution. As this experience grows, the primary outcome that has changed is faster operative times. This increased efficiency does not correlate with compromised outcomes. We continue enrolling patients in our prospective database to strengthen the power of our outcomes analysis.


CuO nanoparticle interaction with human epithelial cells: cellular uptake, location, export, and genotoxicity.
The toxicity of CuO nanoparticles (NPs) to human lung epithelial (A549) cells was investigated in this study. CuO NPs (10-100 mg/L) had significant toxicity to A549 cells, whereas CuO bulk particles (BPs) showed much lower toxicity (24 h IC(50), 58 and 15 mg/L for CuO BPs and NPs, respectively). Transmission electron microscopic analysis demonstrated CuO NP entry into A549 cells and organelles, including lysosomes, mitochondria, and nucleus. Endocytosis was the primary pathway of CuO NPs uptake. CuO NPs (15 mg/L) induced mitochondrial depolarization, possibly mediated by reactive oxygen species (ROS) generation. Intracellular CuO NPs first generate ROS, which subsequently induces the expression of p38 and p53 and ultimately causes DNA damage (Comet assay). We confirm for the first time that the primary cytotoxic response is oxidative stress rather than DNA damage. A fraction of the CuO NPs was exported to the extracellular environment. In this study, centrifugal ultrafiltration tubes were successfully employed to determine the dissolved Cu(2+) from CuO NPs in the cell medium. Dissolved Cu(2+) ions contributed less than half of the total toxicity caused by CuO NPs, including ROS generation and DNA damage. This study provided useful data for understanding transport and toxicity of metal oxide NPs in human cells.


A review of the genus Labeo (Teleostei: Cyprinidae) in Sri Lanka.
The taxonomy of the three native taxa assigned to the genus Labeo (L. dussumieri, L. fisheri and L. porcellus lankae) in Sri Lanka is reviewed. The population hitherto identified as L. dussumieri in Sri Lanka is shown to be a distinct species, here named L. heladiva. Labeo heladiva, new species, has a wide distribution in the low and mid-elevations of the island and is distinguished from its Indian congeners by the combination of having two pairs of barbels; 12-13 branched dorsal-fin rays; lateral line with 44-51 scales; ½8-½9+1+6-7 scales in transverse series; and 19-22 circumpeduncular scales. It differs from its closest relative, L. dussumieri, principally by having 44-51 vs. 50-60 lateral-line scales, 19-22 vs. 22-27 circumpeduncular scales, and by uncorrected pairwise genetic distances of 1.27-2.22% and 1.88-2.91% for the two mitochondrial genes COI and cytb, respectively. Labeo fisheri, which is endemic to the upper reaches of the Mahaweli River basin in the Knuckles mountain range and the central hills in the vicinity of Kandy, is distinguished from Indian congeners by having (in combination) only a single pair of barbels; dorsal fin with 10-12 branched rays; lateral line with 37-39 scales; 7+1+4½-6 scales in transverse series; and 17-20 circumpeduncular scales. Labeo lankae is recognized as a valid species endemic to Sri Lanka. Long suspected to have become extinct, or known only from spurious records, an extant population is reported from the northern dry zone of the island. Labeo lankae is the sister species of L. porcellus of peninsular India; it can be distinguished from its congeners by having, in combination, 10-12 branched dorsal-fin rays; 36-39 lateral-line scales; ½8+1+5-6½ scales in transverse series; and 21-24 circumpeduncular scales. It differs from L. porcellus principally by having ½8 (vs. ½6-½7) scales between the origin of the dorsal fin and the lateral line, 21-24 (vs. 20-21) circumpeduncular scales and uncorrected pairwise genetic distances of 1.27% and 1.41% for the mitochondrial genes COI and cytb, respectively. The three species of Labeo in Sri Lanka do not form a monophyletic group.


Interferon-treated cells release vesicular stomatitis virus particles lacking glycoprotein spikes: correlation with biochemical data.
Earlier we reported a reduction to 1/30th-1/100th of the original number of infectious particles in the infectious vesicular stomatitis virus (VSV) released from L cells treated with 10 or 30 reference units of interferon per ml. However, in these cultures virus particle production, as measured by VSV particle-associated viral RNA, virus nucleocapsid protein, and viral transcriptase, was inhibited by less than 10%. Data reported in this paper show that there was a significant reduction in glycoprotein and membrane protein of VSV particles released from interferon-treated cells. Evidence supporting the deficiency of glycoprotein in VSV released from interferon-treated cells was derived from electron microscopic studies. Under conditions where glycoprotein spikes or projections were clearly detectable on the surface of VSV released from cells not treated with interferon, very few spikes were observed on VSV released from interferon-treated cells. These results suggested that interferon-treated cells produced VSV particles with low infectivity and that this low infectivity may be related to the reduced amount of glycoprotein and membrane protein incorporated into such particles.


Comfort and incidence of abnormal serum sodium, BUN, creatinine and osmolality in dehydration of terminal illness.
This prospective clinical study was undertaken to evaluate the effect of spontaneous food/fluid intake on serum sodium and comfort levels in a population of terminal patients (n = 31) receiving clysis or intravenous hydration. The median and mode of serum sodium were within normal limits and 56 percent of the patients were eunatremic. There was no statistically significant difference in comfort scores between predehydration and dehydration phases, and 85 percent had an optimal comfort score. A statistically significant difference was found (p < 0.5) between mean daily comfort scores of those with normal sodium versus those with abnormal sodium; those with hypernatremia were lower but still in the top third comfort levels. Because the sodium was tested using a Chem7, we also were able to calculate the BUN, creatinine, and osmolality. These are presented and compared to other study results. The findings of this study reinforce the belief that fluid depletion in dying patients results in relatively benign symptoms, that serum sodium levels are not always altered with limited intake and that comfort levels can be maintained when the serum sodium is abnormal.


Bistability of anderson localized States in nonlinear random media.
We study wave transmission through one-dimensional random nonlinear structures and predict a novel effect resulting from an interplay of nonlinearity and disorder. We reveal that, while weak nonlinearity does not change the typical exponentially small transmission in the regime of the Anderson localization, it affects dramatically the disorder-induced localized states excited inside the medium leading to bistable and nonreciprocal resonant transmission. Our numerical modeling shows an excellent agreement with theoretical predictions based on the concept of a high-Q resonator associated with each localized state. This offers a new way for all-optical light control employing statistically homogeneous random media without regular cavities.


Molecular genetics of primary congenital glaucoma in Brazil.
To determine the distribution of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma (PCG). PCG diagnosis was established by presence of buphthalmos in at least one affected eye and associated high intraocular pressures before the age of 3 years. CYP1B1 mutation screening of 52 patients with PCG was performed by SSCP and direct sequencing of PCR fragments. Eleven mutations, four of which are novel, were observed in 26 (50%) individuals. A new frameshift mutation (4340delG) was observed in 20.2% of all individuals screened. These individuals had early-onset, bilateral glaucoma that necessitated multiple surgical interventions. CYP1B1 mutations were twice as frequent in affected individuals of European descent as in individuals of African descent. Analysis of six intragenic single nucleotide polymorphisms (SNPs) established 5'-C-C-G-G-T-A-3' as the most common haplotype among the affected Brazilian individuals. A nonsense mutation (W57X) previously reported in an individual with Peters anomaly (compound heterozygote) was also observed in two individuals with PCG but combined with different mutations. A newly developed SSCP assay enabled us to detect all DNA mutations and polymorphisms previously detected by direct sequencing. Our results indicate that CYP1B1 mutations may be responsible for half of cases of PCG in the Brazilian population. The SNP haplotype 5'-C-C-G-G-T-A-3' was associated with the majority of CYP1B1 mutations. This haplotype harbors the high-activity V432 allele, which is emerging as a putative susceptibility factor in several cancers.


Suitability of pharmaceuticals and personal care products (PPCPs) and artificial sweeteners (ASs) as wastewater indicators in the Pearl River Delta, South China.
Wastewater indicator is a useful tool for evaluating the wastewater impact on natural water, but there is little information about the suitability of wastewater indicators for different regions. This study aimed to select suitable wastewater indicators in the Pearl River Delta region, south China by screening a range of wastewater related organic compounds. The screening campaign was carried out by investigating the occurrence and removal efficiencies of 93 pharmaceuticals and personal care products (PPCPs) and 5 artificial sweeteners (ASs) in nine wastewater treatment plants (WWTPs) located in the region, and the occurrence of these target compounds in the contaminated and clean surface water of the Pearl River. An ideal wastewater indicator should be hydrophilic, source-specific for domestic wastewater, ubiquitous in contaminated surface water with detection frequency (DF) >80% and absent in background water samples. For liable indicators, high removal rates (>90%) should be observed in WWTPs and they should be detected in all the influent samples at concentrations fifty times higher than their limits of quantification. For conservative indicators, low removal rates (<50%) should be observed in WWTPs and they should be detected in all the effluent samples at concentrations fifty times higher than their limits of quantification. Based on the above criteria, sucralose and fluconazole were selected as conservative indicators in the region, while cyclamate, saccharin, methyl paraben, ethyl paraben, propyl paraben, paracetamol, salicylic acid and caffeine were selected as liable indicators.


Type 3 renal tubular acidosis.
Renal tubular acidosis (RTA) is a group of transport defects in the reabsorption of bicarbonate, the excretion of hydrogen ion (H(+)), or both, resulting in systemic acidosis and hypokalemia with a normal glomerular filtration rate. Although isolated proximal (type 2) or distal (type 1) tubular pathologies are well characterized, a combined pathology leading to type 3 RTA is very rare. Here, we report a case of type 3 RTA, using an algorithmic approach to classify a scenario of hypokalemic metabolic acidosis in the setting of episodic flaccid paralysis.


Typical prenatal vitamin D supplement intake does not prevent decrease of plasma 25-hydroxyvitamin D at birth.
The objective of this longitudinal study was to determine what typical vitamin D predictors influence the change in vitamin D status from mid-pregnancy to birth. Plasma 25-hydroxyvitamin D [25(OH)D] was determined at mid-pregnancy (8-20 weeks gestation) and following birth (n = 193). Usual predictors of vitamin D status [body mass index (BMI), race, season] in addition to prenatal supplemental vitamin D intake and docosahexaenoic acid (DHA) status at delivery were assessed for their interaction on the change on plasma 25(OH)D concentration between the two time points. Forty-nine percent of women had inadequate vitamin D status [categorized as deficient (<30 nmol/L) or insufficient (30-49.9 nmol/L) by IOM guidelines] at mid-pregnancy and 82% were deficient or insufficient at birth. Plasma 25(OH)D concentration dropped 61% from mid-pregnancy to birth. Season of birth (F = 7.86, P = 0.006) and mid-pregnancy plasma 25(OH)D concentration (F = 6.17, P = 0.014) were significant variables in the change of vitamin D status while BMI, race, DHA status, and typical vitamin D intake (334 IU/day) from prenatal supplements did not have an effect. Women who delivered in summer and fall had a 1.5-fold greater plasma 25(OH)D concentration than women who delivered in winter in spring (41.1 ± 23.1 and 40.7 ± 20.5 nmol/L summer and fall, respectively, versus 27.7 ± 17.9 and 29.3 ± 21.4 nmol/L in winter and spring, respectively). Typical supplemental vitamin D intake during pregnancy did not prevent precipitous drops in maternal plasma 25(OH)D concentration. Clinicians and dietitians should be aware of the risk of inadequate vitamin D status in pregnant women in the United States relative to their initial vitamin D status and the season of birth.


Low yield of significant findings on endoscopic retrograde cholangiopancreatography in patients with pancreatobiliary pain and no objective findings.
Due to the challenging nature of the type III sphincter of the Oddi dysfunction (SOD) patient, the suspected low diagnostic yield from endoscopic retrograde cholangiopancreatography (ERCP), the high complication rate, and the potential for litigation it is surprising that diagnostic ERCP continues to be performed in this patient population. The purpose of this study was to determine the incidence of significant findings on ERCP alone in patients with disabling abdominal pain of suspected pancreatobiliary origin and no objective findings. Entry criteria of this study included: (1) ERCP with attempt at visualization of both the biliary tree and pancreatic duct, (2) suspected of having abdominal pain of pancreatobiliary origin, (3) biliary or pancreatic type III by the modified Geenen-Hogan classification, (4) never undergone sphincterotomy, (5) attempted manometry of both sphincters. A total of 265 patients met entry criteria. Significant findings were found in seven patients (2.6 %): choledococoele (1), anomalous pancreatobiliary ductal union (2), mild-moderate chronic pancreatitis (2), and pancreatic duct filling defect suspicious for IPMN (2). Potentially significant in 25 patients (9.4 %) were: equivocal chronic pancreatitis (1), incomplete (4) and complete pancreas divisum (20). SOD was diagnosed in 77.7 %. 11.3 % had undergone a previous diagnostic ERCP. ERCP in this high-risk population requires detailed informed consent, availability of SOM to increase the diagnostic yield, and skills in placing prophylactic pancreatic stents. It is our belief that patients without objective findings of pancreatobiliary disease that would explain their subjective complaints should not undergo diagnostic ERCP.


Effect of vascular endothelial growth factor on nitric oxide production by cultured rat mesangial cells.
Vascular endothelial growth factor (VEGF) stimulates nitric oxide (NO) production by endothelial cells in vitro and in vivo. However, the impact of VEGF on inducible nitric oxide synthase (iNOS) activity and NO synthesis in cultured mesangial cells is not known. Therefore, we measured nitrite accumulation in cytokine-stimulated, rat mesangial cells (RMC) in response to graded concentrations of VEGF. Addition of VEGF (10-50 ng/ml) did not alter RMC viability or NO production in either normal (5.6 mM) or high (33.3 mM) glucose conditions. Exposure of RMC to VEGF did not modify the effects of L-arginine (20 mM) or L-NAME (1 mM) on nitrite accumulation in normal or high glucose media. The steady state abundance of iNOS mRNA and the cytosolic content of iNOS protein were unaffected by addition of VEGF. Cultured RMC expressed the high-affinity tyrosine kinase VEGF receptors, flt and flk/KDR, and the levels were not modulated by incubation in normal or high glucose media. We conclude that VEGF does not regulate proliferation or NO production in cultured RMC. These findings suggest that disturbances in the normal interaction between VEGF and NO are not involved in the pathogenesis of abnormal mesangial cell structure or function in diabetic nephropathy.