Yoga training improves metabolic parameters in obese boys.
Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7±0.5 years, n=10) and control groups (age 14.6±1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p<0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p<0.01). HDL-cholesterol was decreased in both groups (p<0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys.


Training-induced changes in inhibitory control network activity.
Despite extensive research on inhibitory control (IC) and its neural systems, the questions of whether IC can be improved with training and how the associated neural systems change are understudied. Behavioral evidence suggests that performance on IC tasks improves with training but that these gains do not transfer to other tasks, and almost nothing is known about how activation in IC-related brain regions changes with training. Human participants were randomly assigned to receive IC training (N = 30) on an adaptive version of the stop-signal task (SST) or an active sham-training (N = 30) during 10 sessions across 3 weeks. Neural activation during the SST before and after training was assessed in both groups using functional magnetic resonance imaging. Performance on the SST improved significantly more in the training group than in the control group. The pattern of neuroimaging results was consistent with a proactive control model such that activity in key parts of the IC network shifted earlier in time within the trial, becoming associated with cues that anticipated the upcoming need for IC. Specifically, activity in the inferior frontal gyrus decreased during the implementation of control (i.e., stopping) and increased during cues that preceded the implementation of IC from pretraining to post-training. Also, steeper behavioral improvement in the training group correlated with activation increases during the cue phase and decreases during implementation in the dorsolateral prefrontal cortex. These results are the first to uncover the neural pathways for training-related improvements in IC and can explain previous null findings of IC training transfer.


Spatiotemporal expression patterns of slit and robo genes in the rat brain.
Diffusible chemorepellents play a major role in guiding developing axons toward their correct targets by preventing them from entering or steering them away from certain regions. Genetic studies in Drosophila revealed a repulsive guidance system that prevents inappropriate axons from crossing the central nervous system midline; this repulsive system is mediated by the secreted extracellular matrix protein Slit and its receptors Roundabout (Robo). Three distinct slit genes (slit1, slit2, and slit3) and three distinct robo genes (robo1, robo2, rig-1) have been cloned in mammals. However, to date, only Robo1 and Robo2 have been shown to be receptors for Slits. In rodents, Slits have been shown to function as chemorepellents for several classes of axons and migrating neurons. In addition, Slit can also stimulate the formation of axonal branches by some sensory axons. To identify Slit-responsive neurons and to help analyze Slit function, we have studied, by in situ hybridization, the expression pattern of slits and their receptors robo1 and robo2, in the rat central nervous system from embryonic stages to adult age. We found that their expression patterns are very dynamic: in most regions, slit and robo are expressed in a complementary pattern, and their expression is up-regulated postnatally. Our study confirms the potential role of these molecules in axonal pathfinding and neuronal migration. However, the persistence of robo and slit expression suggests that the couple slit/robo may also have an important function in the adult brain.


Prognosis and Histological Classification in Elderly Patients with ANCA-Glomerulonephritis: A Registry-Based Cohort Study.
The value of a histologic classification scheme to classify patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) into focal, mixed, crescentic, and sclerotic types for predicting risk of end-stage renal disease (ESRD) is well documented. However, the prognostic value of histological classification specifically in elderly patients (≥70 years) with ANCA-GN has not previously been investigated. Patients with biopsy-verified pauci-immune necrotizing glomerulonephritis were identified from the Norwegian Kidney Biopsy Registry between 1991 and 2012 and those ≥70 years of age at the time of diagnosis and having positive anti-neutrophil cytoplasmic antibody serology were included in this study. The incidence rate of ESRD and/or death was determined by linking the study cohort to the Norwegian Renal Registry and the Population Registry of Norway. The ESRD-free survival and patient survival were compared between the 4 histological types. Of the 81 patients included, 20 progressed to ESRD and 34 died. The 1-year and 5-year ESRD-free survival varied between histological groups (p = 0.003) as follows: focal, 97% and 97%, respectively; mixed, 70% and 57%; crescentic, 76% and 63%; and sclerotic, 49% and 49%. Patient survival did not differ significantly between groups (p = 0.30). Histological classification in elderly patients with ANCA-GN is useful for predicting ESRD but not survival.


Current Concepts and New Trends in the Treatment of Cardiogenic Shock Complicating Acute Myocardial Infarction.
Cardiogenic shock (CS) is a critical condition which often complicates the evolution of an acute myocardial infarction (AMI). At the same time, co-existence of chronic multi-vessel disease can lead to the development of cardiogenic shock in cases with pronounced haemodynamic instability. Different clinical studies have tried to identify the most appropriate treatment for critical cases of CS complicating AMI. This review aims to present the current status of recommended therapeutic strategies for severe cases of CS presenting as a complication of AMI, and try to shed light on the most appropriate therapeutic strategy as outlined in the current literature. The paper will discuss the different current strategies available for use in the treatment of this condition, includig interventional revascularisation, (complete or culprit), the role of new devices for providing mechanical circulatory support, and the potential role of new drug therapies and of hypothermia.


Hypoglycemic and Hypolipemic Effects of a New Lecithin Formulation of Bergamot Polyphenolic Fraction: A Double Blind, Randomized, Placebo- Controlled Study.
Hyperlipemia represents an independent risk factor in the development of atherosclerosis in patients undergoing type 2 diabetes mellitus (DM). Moreover, the pharmacological treatment of dyslipemia in patients undergoing type 2 DM (e.g. by means of statins), is accompanied by relevant side effects and oral supplementation with natural antioxidants, such as Citrus polyphenols, has recently been suggested to improve cardioprotection in such patients. However, due to the poor gastrointestinal absorption of polyphenols, novel formulations have recently been developed for getting a better bioavailability of polyphenolic rich fractions of citrus species extract rich in polyphenols. Here, we investigated the effect of standard bergamot polyphenolic fraction (BPF®) as well as of its phytosomal formulation (BPF Phyto), in patients with type 2 DM and hyperlipemia. A randomized, double blind, placebo-controlled study was carried out in 60 patients suffering from type 2 DM and mixed hyperlipemia. Patients were divided into three groups: one receiving placebo, the second receiving standard BPF and the third BPF Phyto. In the groups receiving BPF and BPF Phyto, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides accompanied by increased HDL cholesterol was observed. This effect was associated with significant reduction of small dense atherogenic LDL particles, as detected by means of proton NMR Spectroscopy, thus confirming the hypolipemic and hypoglycemic effect of bergamot extract both when using standard formulation as well as BPF Phyto. No differences were seen in the therapeutic response among groups receiving BPF and BPF Phyto, thus suggesting a substantial bioequivalence in their hypoglycemic and hypolipemic profile. However, when comparing the pharmacokinetic profile of naringin (the major component of BPF) and its metabolites, in patients treated with BPF Phyto, an at least 2,5 fold increase in its absorption was found, confirming in human studies the better profile of BPF Phyto compared to standard BPF. These data suggest that better absorption and tissue distribution of BPF Phyto formulation represents an innovative approach in supplementation treatments of cardiometabolic disorders.


Quantifying the brain's sheet structure with normalized convolution.
The hypothesis that brain pathways form 2D sheet-like structures layered in 3D as "pages of a book" has been a topic of debate in the recent literature. This hypothesis was mainly supported by a qualitative evaluation of "path neighborhoods" reconstructed with diffusion MRI (dMRI) tractography. Notwithstanding the potentially important implications of the sheet structure hypothesis for our understanding of brain structure and development, it is still considered controversial by many for lack of quantitative analysis. A means to quantify sheet structure is therefore necessary to reliably investigate its occurrence in the brain. Previous work has proposed the Lie bracket as a quantitative indicator of sheet structure, which could be computed by reconstructing path neighborhoods from the peak orientations of dMRI orientation density functions. Robust estimation of the Lie bracket, however, is challenging due to high noise levels and missing peak orientations. We propose a novel method to estimate the Lie bracket that does not involve the reconstruction of path neighborhoods with tractography. This method requires the computation of derivatives of the fiber peak orientations, for which we adopt an approach called normalized convolution. With simulations and experimental data we show that the new approach is more robust with respect to missing peaks and noise. We also demonstrate that the method is able to quantify to what extent sheet structure is supported for dMRI data of different species, acquired with different scanners, diffusion weightings, dMRI sampling schemes, and spatial resolutions. The proposed method can also be used with directional data derived from other techniques than dMRI, which will facilitate further validation of the existence of sheet structure.


Characterization and compilation of polymorphic simple sequence repeat (SSR) markers of peanut from public database.
There are several reports describing thousands of SSR markers in the peanut (Arachis hypogaea L.) genome. There is a need to integrate various research reports of peanut DNA polymorphism into a single platform. Further, because of lack of uniformity in the labeling of these markers across the publications, there is some confusion on the identities of many markers. We describe below an effort to develop a central comprehensive database of polymorphic SSR markers in peanut. We compiled 1,343 SSR markers as detecting polymorphism (14.5%) within a total of 9,274 markers. Amongst all polymorphic SSRs examined, we found that AG motif (36.5%) was the most abundant followed by AAG (12.1%), AAT (10.9%), and AT (10.3%).The mean length of SSR repeats in dinucleotide SSRs was significantly longer than that in trinucleotide SSRs. Dinucleotide SSRs showed higher polymorphism frequency for genomic SSRs when compared to trinucleotide SSRs, while for EST-SSRs, the frequency of polymorphic SSRs was higher in trinucleotide SSRs than in dinucleotide SSRs. The correlation of the length of SSR and the frequency of polymorphism revealed that the frequency of polymorphism was decreased as motif repeat number increased. The assembled polymorphic SSRs would enhance the density of the existing genetic maps of peanut, which could also be a useful source of DNA markers suitable for high-throughput QTL mapping and marker-assisted selection in peanut improvement and thus would be of value to breeders.


Genetic effects of captive breeding cause a rapid, cumulative fitness decline in the wild.
Captive breeding is used to supplement populations of many species that are declining in the wild. The suitability of and long-term species survival from such programs remain largely untested, however. We measured lifetime reproductive success of the first two generations of steelhead trout that were reared in captivity and bred in the wild after they were released. By reconstructing a three-generation pedigree with microsatellite markers, we show that genetic effects of domestication reduce subsequent reproductive capabilities by approximately 40% per captive-reared generation when fish are moved to natural environments. These results suggest that even a few generations of domestication may have negative effects on natural reproduction in the wild and that the repeated use of captive-reared parents to supplement wild populations should be carefully reconsidered.


How contextual and relational aspects shape the perspective of healthcare providers on decision making for patients with disorders of consciousness: a qualitative interview study.
Disorders of consciousness (DOC) are a family of related neurological syndromes characterized by deficits of varying degrees of wakefulness (e.g., sleep-wake cycles and arousal) or awareness (e.g., reacting to stimuli, interacting with the environment). Although coma rarely persists for more than a few weeks, some patients remain in a subsequent vegetative state or a minimally conscious state for months or years. Caring for patients with DOC raises ethical questions, but the perspectives of healthcare providers on these questions remain poorly documented. We conducted a qualitative study involving healthcare providers with different backgrounds. Semistructured interviews were used to explore attitudes toward ethical issues. We found that contextual (e.g., time, resource allocation) and relational aspects (e.g., communication process, families) shaped how ethical challenges surfaced and were managed. We call for greater awareness of contextual, institutional and social aspects and focus on these issues in training programs.


Exercises for mechanical neck disorders.
Neck disorders are common, disabling and costly. The effectiveness of exercise as a physiotherapy intervention remains unclear. To improve pain, disability, function, patient satisfaction, quality of life and global perceived effect in adults with neck pain. Computerized searches were conducted up to February 2012. We included single therapeutic exercise randomized controlled trials for adults with neck pain with or without cervicogenic headache or radiculopathy. Two review authors independently conducted selection, data extraction, 'Risk of bias' assessment, and clinical relevance. The quality of the body of evidence was assessed using GRADE. Relative risk and standardized mean differences (SMD) were calculated. After judging clinical and statistical heterogeneity, we performed meta-analyses. Six of the 21 selected trials had low risk of bias. Moderate quality evidence shows that combined cervical, scapulothoracic stretching and strengthening are beneficial for pain relief post treatment (pooled SMD -0.35, 95% confidence interval (CI): -0.60, -0.10) and at intermediate follow-up (pooled SMD -0.31, 95% CI: -0.57, -0.06), and improved function short term and intermediate term (pooled SMD -0.45, 95% CI: -0.72, -0.18) for chronic neck pain. Moderate quality evidence demonstrates patients are very satisfied with their care when treated with therapeutic exercise. Low quality evidence shows exercise is of benefit for pain in the short term and for function up to long-term follow-up for chronic neck pain. Low to moderate quality evidence shows that chronic neck pain does not respond to upper extremity stretching and strengthening or a general exercise program.Low to moderate quality evidence supports self-mobilization, craniocervical endurance and low load cervical-scapular endurance exercises in reducing pain, improving function and global perceived effect in the long term for subacute/chronic cervicogenic headache. Low quality evidence supports neck strengthening exercise in acute cervical radiculopathy for pain relief in the short term. Low to moderate quality evidence supports the use of specific cervical and scapular stretching and strengthening exercise for chronic neck pain immediately post treatment and intermediate term, and cervicogenic headaches in the long term. Low to moderate evidence suggests no benefit for some upper extremity stretching and strengthening exercises or a general exercise program. Future trials should consider using an exercise classification system to establish similarity between protocols and adequate sample sizes. Factorial trials would help determine the active treatment agent within a treatment regimen where a standardized representation of dosage is essential. Standardized reporting of adverse events is needed for balancing the likelihood of treatment benefits over potential harms.


An economic decision support tool for simulating paratuberculosis control strategies in a UK suckler beef herd.
A dynamic, deterministic, economic simulation model was developed to estimate the costs and benefits of controlling Mycobacterium avium subsp. paratuberculosis (Johne's disease) in a suckler beef herd. The model is intended as a demonstration tool for veterinarians to use with farmers. The model design process involved user consultation and participation and the model is freely accessible on a dedicated website. The 'user-friendly' model interface allows the input of key assumptions and farm specific parameters enabling model simulations to be tailored to individual farm circumstances. The model simulates the effect of Johne's disease and various measures for its control in terms of herd prevalence and the shedding states of animals within the herd, the financial costs of the disease and of any control measures and the likely benefits of control of Johne's disease for the beef suckler herd over a 10-year period. The model thus helps to make more transparent the 'hidden costs' of Johne's in a herd and the likely benefits to be gained from controlling the disease. The control strategies considered within the model are 'no control', 'testing and culling of diagnosed animals', 'improving management measures' or a dual strategy of 'testing and culling in association with improving management measures'. An example 'run' of the model shows that the strategy 'improving management measures', which reduces infection routes during the early stages, results in a marked fall in herd prevalence and total costs. Testing and culling does little to reduce prevalence and does not reduce total costs over the 10-year period.


Quality of life can both influence and be an outcome of general health perceptions after heart surgery.
Our aim was to investigate the existence of a reciprocal relationship between patients' assessment of quality of life and their appraisal of health. If present, this relationship will interfere with the interpretation of heart surgery's effect on overall quality of life. Path analysis was used to investigate reciprocal causal relationships between general health perceptions and overall quality of life before and after heart surgery. Longitudinal data from a study of coronary artery bypass surgery were used to model lagged, cross-lagged, and simultaneous paths over four time-points of assessment from before surgery to one year afterwards. The conceptual framework for the analysis was the Wilson and Cleary causal pathway model. General health perceptions were measured with the Short Form 36. Overall quality of life was measured with i) a single question regarding life satisfaction and ii) the multi-item Quality of Life Survey. Acceptable model fit was obtained for reciprocal causation between general health perceptions and overall quality of life. Regression coefficients changed over different phases of rehabilitation. Serial correlation accounted for much of the variance within variables over time. The present analysis demonstrates that unidirectional models of causality are inadequate to explain the effect of heart surgery on overall quality of life. Overall quality of life can causally influence as well as be an outcome of health status after coronary artery bypass surgery.


Complicated grief and its correlates in patients with bipolar disorder.
While the recent loss of a loved one has been identified as a risk factor for suicide in patients with bipolar disorder, and complicated grief (CG) has been associated with elevated rates of suicidality compared with loss without CG, little is known about the frequency or impact of CG in bipolar disorder. We investigated the frequency and implications of loss of loved ones in an ongoing study of bipolar disorder. We conducted a survey of 120 patients with well-characterized DSM-IV bipolar disorder participating in Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a large naturalistic study, in order to identify frequency of loss and to examine the presence of CG and its clinical correlates. Survey data were gathered from October 2003 to March 2004. A lifetime history of a significant loss was reported by 86% (103/120) of participants; 24.3% (25/103) of those met criteria for CG, defined as a score > or = 25 on the Inventory of Complicated Grief (ICG), with a mean +/- SD ICG score of 33.7 +/- 6.9. The presence of CG was associated with elevated rates of panic disorder and alcohol abuse comorbidity, as well as other measures of panic symptoms and phobic avoidance. CG was also associated with a higher rate of lifetime suicide attempts, greater functional impairment, and poorer social support. Our findings suggest the presence of a substantial burden of comorbid grief-related illness and impairment in patients with bipolar disorder. Further research is needed to understand the overlap of anxiety disorders and phobic avoidance in bipolar patients with complicated grief.


[Epidemiology of Lyme borreliosis and neuroborreliosis in France].
Lyme borreliosis (LB) is a systemic disease called neuroborreliosis (NB) when neurological symptoms are pre-eminent. LB is a zoonosis caused by Borrelia bacteria transmitted by Ixodes tick-bite. Because of the absence of a national registry, epidemiology of LB in France is not well known. Moreover, diagnosis of NB may be difficult because of the various clinical forms. Acute meningoradiculitis is the most common presentation, but pauci-symptomatic meningitis, encephalitis, myelitis, polyneuropathy, cerebrovascular involvement, and rarely chronic encephalomyelitis are also described. The vector Ixodes ricinus (I. ricinus) is found throughout metropolitan France excepting border areas of the Mediterranean seaside and in regions with an altitude above 1500 meters. In France, the Borrelia infestation rate of Ixodes is 7% with wide disparity between administrative districts. Prospective work in 1999-2000 by 875 general practitioners participating in the "Sentinel" network established the estimated incidence of BL (9.4/100 000) and of NB (0.6/100 000) in France. Incidence is higher in certain regions: in Alsace, prospective work by 419 general practitioners and specialists in cooperation with the national surveillance agency (Institut national de veille sanitaire), estimated BL incidence at 86 to 200/100 000 inhabitants and NB at 10/100 000. Thus, although globally France is a country with a moderate risk for LB, some regions such as Limousin, Auvergne, Lorraine and Alsace, have a high risk of LB, comparable to countries in the northeastern Europe such as Germany and Sweden.


Species distribution of clinical Acinetobacter isolates revealed by different identification techniques.
A total of 2582 non-duplicate clinical Acinetobacter spp. isolates were collected to evaluate the performance of four identification methods because it is important to identify Acinetobacter spp. accurately and survey the species distribution to determine the appropriate antimicrobial treatment. Phenotyping (VITEK 2 and VITEK MS) and genotyping (16S rRNA and rpoB gene sequencing) methods were applied for species identification, and antimicrobial susceptibility test of imipenem and meropenem was performed with a disk diffusion assay. Generally, the phenotypic identification results were quite different from the genotyping results, and their discrimination ability was unsatisfactory, whereas 16S rRNA and rpoB gene sequencing showed consistent typing results, with different resolution. Additionally, A. pittii, A. calcoaceticus and A. nosocomialis, which were phylogenetically close to A. baumannii, accounted for 85.5% of the non-A. baumannii isolates. One group, which could not be clustered with any reference strains, consisted of 11 isolates and constituted a novel Acinetobacter species that was entitled genomic species 33YU. None of the non-A. baumannii isolates harbored a blaOXA-51-like gene, and this gene was disrupted by ISAba19 in only one isolate; it continues to be appropriate as a genetic marker for A. baumannii identification. The resistance rate of non-A. baumannii isolates to imipenem and/or meropenem was only 2.6%, which was significantly lower than that of A. baumannii. Overall, rpoB gene sequencing was the most accurate identification method for Acinetobacter species. Except for A. baumannii, the most frequently isolated species from the nosocomial setting were A. pittii, A. calcoaceticus and A. nosocomialis.


First Report of Colletotrichum boninense Causing Anthracnose on Pepper in China.
Anthracnose, caused by Colletotrichum spp., is a severe disease and results in large losses in pepper (Capsicum frutescens) production in China (4). Colletotrichum boninense is one of the Colletotrichum species in pepper in China. In August 2011, anthracnose symptoms (circular, sunken lesions with orange to black spore masses) were observed on pepper fruits in De-Yang, Sichuan Province, China. Three single-spore isolates (SC-6-1, SC-6-2, SC-6-3) were obtained from the infected fruits. A 5-mm diameter plug was transferred to potato dextrose agar (PDA); the isolates formed colonies with white margins and circular, dull orange centers. The conidia were cylindrical, obtuse at both ends, and 10.5 to 12.6 × 4.1 to 5.0 μm. The colonies grew rapidly at 25 to 28°C, and the average colony diameter was 51 to 52 mm after 5 days on PDA at 25°C. Based upon these characters, the causal agent was identified as C. boninense. To confirm the identity of the isolates, the internal transcribed spacer (ITS) regions were amplified with the ITS1/ITS4 universal primers (1). The internal transcribed spacer (ITS) sequences (Accession No. JQ926743) of the causal fungus shared 99 to 100% homology with ITS sequences of C. boninense in GenBank (Accession Nos. FN566865 and EU822801). The identity of the causal agent as C. boninense was also confirmed by species-specific primers (Col1/ITS4) (2). In a pathogenicity test, five detached ripe pepper fruits were inoculated with 1 μl of a conidial suspension (106 conidia/mL) or five fruits with 1 μl of sterile water were kept as control. After 7 days in a moist chamber at 25°C, typical anthracnose symptoms had developed on the five inoculated fruits but not on control fruits. C. boninense was reisolated from the lesions, and which was confirmed by morphology and molecular methods as before. There have reports of C. boninense infecting many species of plants, including pepper (3). To our knowledge, this is the first report of C. boninense causing anthracnose on pepper in China. References: (1) A. K. Lucia et al. Phytopathology 93:581, 2002. (2) S. A. Pileggi et al. Can. J. Microbiol. 55:1081, 2009. (3) H. J. Tozze et al. Plant Dis. 93:106, 2009. (4) M. L. Zhang. J. Anhui Agri. Sci. 2:21, 2000.


Indole based tubulin polymerization inhibitors: An update on recent developments.
The exploration of cancer microenvironment and its physiology have exposed a number of potential molecular targets for selective therapeutic intervention by anti-cancer agents. Microtubules are basic cell components formed by polymerization of αβ heterodimers which play a pivotal role in cellular functions as well as cell division. Drugs that can control the microtubule assembly either by hindering tubulin polymerization or by obstructing microtubule disassembly are of great importance in anti-cancer therapy. Diverse classes of naturally occurring as well as synthetic and semi-synthetic compounds with an indole nucleus induce microtubule polymerization and depolymerization and thereby change tubulin dynamics. Rapid development of several novel tubulin polymerization inhibitors has been observed over the past few years and some of them have associated vascular disrupting properties too. The present review starts with the structure, function and importance of microtubules in a eukaryotic cell. The well characterized tubulin binding domains and the corresponding inhibitors including their mechanism of action is also a part of this article. The report mainly focuses on the brief synthetic methodology with the relevant SAR studies of different indole derived molecules that have been reported in the past few years as potential inhibitors of tubulin polymerization is discussed. This review will provide the up-to-date evidence-base for synthetic chemists as well as biologists to design and synthesize new active molecules to inhibit tubulin polymerization.


Tricuspid Atresia with Non-compaction: An Early Experience with Implications for Surgical Palliation.
Left ventricle non-compaction (LVNC) has worse outcomes when associated with congenital heart defects (CHD). The co-occurrence and outcomes of LVNC with tricuspid atresia (TA) are not well described. Our study aims to determine the prevalence of LVNC with functionally single ventricle due to TA, and to describe the early outcomes of surgical palliation. A retrospective database search for patients (n = 167,566) and echocardiograms (n = 44,053) was performed in order to collect clinical, echocardiographic, and hemodynamic data of pediatric patients with TA and LVNC at St. Louis Children's Hospital, Missouri, USA, from January 1, 2008, to August 31, 2013. The prevalence of TA and LVNC was 0.015 and 0.08%, respectively. Eight patients with TA had LVNC (32%, group 1). Seventeen patients had only TA (68%, group 2). Five patients from group 1 and 8 patients from group 2 were surgically palliated with the Fontan procedure. They exhibited similar remodeling indices, and hemodynamics (median LV end-diastolic pressure ≤10 mmHg; median mean pulmonary artery pressure ≤15 mmHg) that allowed for completion of the Fontan procedure. All Fontan patients were in New York Heart Association class I after a 3-year (median) follow-up period. Our data show that TA with LVNC patients, who have acceptable cardiac remodeling indices, LV systolic function, and hemodynamics (LVEDP ≤ 10 mmHg, mean pulmonary artery pressure ≤ 15 mmHg) can have successful completion of the Fontan procedure and positive early outcomes.


The psychology of negative-sum competition in strategic interactions.
Many real-life examples-from interpersonal rivalries to international conflicts-suggest that people actively engage in competitive behavior even when it is negative sum (benefiting the self at a greater cost to others). This often leads to loss spirals where everyone-including the winner-ends up losing. Our research seeks to understand the psychology of such negative-sum competition in a controlled setting. To do so, we introduce an experimental paradigm in which paired participants have the option to repeatedly perform a behavior that causes a relatively small gain for the self and a larger loss to the other. Although they have the freedom not to engage in the behavior, most participants actively do so and incur substantial losses. We propose that an important reason behind the phenomena is shallow thinking-focusing on the immediate benefit to the self while overlooking the downstream consequences of how the behavior will influence their counterparts' actions. In support of the proposition, we find that participants are less likely to engage in negative-sum behavior, if they are advised to consider the downstream consequences of their actions, or if they are put in a less frenzied decision environment, which facilitates deeper thinking (acting in discrete vs. continuous time). We discuss how our results differ from prior findings and the implications of our research for mitigating negative-sum competition and loss spirals in real life. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Electronic clinical decision support for children with minor head trauma and intracranial injuries: a sociotechnical analysis.
Current management of children with minor head trauma (MHT) and intracranial injuries is not evidence-based and may place some children at risk of harm. Evidence-based electronic clinical decision support (CDS) for management of these children may improve patient safety and decrease resource use. To guide these efforts, we evaluated the sociotechnical environment impacting the implementation of electronic CDS, including workflow and communication, institutional culture, and hardware and software infrastructure, among other factors. Between March and May, 2020 semi-structured qualitative focus group interviews were conducted to identify sociotechnical influences on CDS implementation. Physicians from neurosurgery, emergency medicine, critical care, and pediatric general surgery were included, along with information technology specialists. Participants were recruited from nine health centers in the United States. Focus group transcripts were coded and analyzed using thematic analysis. The final themes were then cross-referenced with previously defined sociotechnical dimensions. We included 28 physicians and four information technology specialists in seven focus groups (median five participants per group). Five physicians were trainees and 10 had administrative leadership positions. Through inductive thematic analysis, we identified five primary themes: (1) clinical impact; (2) stakeholders and users; (3) tool content; (4) clinical practice integration; and (5) post-implementation evaluation measures. Participants generally supported using CDS to determine an appropriate level-of-care for these children. However, some had mixed feelings regarding how the tool could best be used by different specialties (e.g. use by neurosurgeons versus non-neurosurgeons). Feedback from the interviews helped refine the tool content and also highlighted potential technical and workflow barriers to address prior to implementation. We identified key factors impacting the implementation of electronic CDS for children with MHT and intracranial injuries. These results have informed our implementation strategy and may also serve as a template for future efforts to implement health information technology in a multidisciplinary, emergency setting.


Antibacterial effect of chlorhexidine-cetrimide combination, Salvia officinalis plant extract and octenidine in comparison with conventional endodontic irrigants.
The aim of the present study was to compare the antimicrobial effect of sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX), a CHX/cetrimide solution (CHX+CTR), octenidine hydrochloride (OCT) and Salvia officinalis plant extract against Enterococcus faecalis. Seventy decoronated single-rooted human teeth were infected and divided into 6 test (n=10) and 2 control groups (n=5) (negative, sterile samples and positive, infected samples). Following irrigants were then applied to test groups: 2.5% NaOCl, 5.25% NaOCl, CHX, CHX+CTR, S. officinalis extract and OCT. The dentin chips were obtained from inner root canal walls and analyzed by counting the number of colony forming units (CFU). The 2.5% NaOCl, 5.25% NaOCl, CHX and OCT groups presented no bacterial growth (CFU=0). S. officinalis and CHX+CTR groups reduced the number of E. faecalis cells but could not eliminate all. OCT may have potential as an endodontic irrigant in treatment of infected root canals.


Room-temperature ferroelectricity and a switchable diode effect in two-dimensional α-In2Se3 thin layers.
Nanoscale room-temperature ferroelectricity is ideal for developing advanced non-volatile high-density memories. However, reaching the thin film limit in conventional ferroelectrics is a long-standing challenge due to the presence of the critical thickness effect. van der Waals materials, thanks to their stable layered structure, saturated interfacial bonding and weak interlayer couplings, are promising for exploring ultra-thin two-dimensional (2D) ferroelectrics and device applications. Here, we demonstrate a switchable room-temperature ferroelectric diode built upon a 2D ferroelectric α-In2Se3 layer as thin as 5 nm in the form of a graphene/α-In2Se3 heterojunction. The intrinsic out-of-plane ferroelectricity of the α-In2Se3 thin layers is evidenced by the observation of reversible spontaneous electric polarization with a relatively low coercive electric field of ∼2 × 105 V cm-1 and a typical ferroelectric domain size of around tens μm2. Owing to the out-of-plane ferroelectricity of the α-In2Se3 layer, the Schottky barrier at the graphene/α-In2Se3 interface can be effectively tuned by switching the electric polarization with an applied voltage, leading to a pronounced switchable double diode effect with an on/off ratio of ∼105. Our results offer a new way for developing novel nanoelectronic devices based on 2D ferroelectrics.


Can implementation intentions and text messages promote brisk walking? A randomized trial.
To test the efficacy in promoting brisk walking of two theory-based interventions that incorporate implementation intentions and text message (Short Message Service; SMS) reminders directed at one's walking-related plans or goals. Participants (N = 149) were randomized to one of three conditions (implementation intention + SMS plan reminder, implementation intention + SMS goal reminder, control) before completing measures at baseline and follow-up 4 weeks later. At follow-up, the experimental groups were given a surprise recall task concerning their plans. All participants completed an equivalent goal recall task. Validated self-report measures of physical activity and measures of implementation intention and goal recall, weight, and waist-to-hip ratio. Both intervention groups increased their brisk walking relative to the control group, without reducing other physical activity. The goal reminder group lost the most weight. The SMS plan reminder group recalled more of their plans than the SMS goal reminder group, but the latter were more successful in goal recall. Both interventions can promote brisk walking in sedentary populations. Text messages aid the recall of, and could enhance interventions that target, implementation intentions and goals.


Prolactin-secreting tumors and hypogonadism in 22 men.
We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism.


Differential effects of combined N sources on early steps of the Nod factor-dependent transduction pathway in Lotus japonicus.
The development of nitrogen-fixing nodules in legumes is induced by perception of lipochitin-oligosaccharide signals secreted by a bacterial symbiont. Nitrogen (N) starvation is a prerequisite for the formation, development, and function of root nodules, and high levels of combined N in the form of nitrate or ammonium can completely abolish nodule formation. We distinguished between nitrate and ammonium inhibitory effects by identifying when and where these combined N sources interfere with the Nod-factor-induced pathway. Furthermore, we present a small-scale analysis of the expression profile, under different N conditions, of recently identified genes involved in the Nod-factor-induced pathway. In the presence of high levels of nitrate or ammonium, the NIN gene fails to be induced 24 h after the addition of Nod factor compared with plants grown under N-free conditions. This induction is restored in the hypernodulating nitrate-tolerant har1-3 mutant only in the presence of 10 and 20 mM KNO3. These results were confirmed in Lotus plants inoculated with Mesorhizobium loti. NIN plays a key role in the nodule organogenesis program and its downregulation may represent a crucial event in the nitrate-dependent pathway leading to the inhibition of nodule organogenesis.


Late-Start Days Increase Total Operative Time in Microvascular Breast Reconstruction.
Prolonged operative time has been associated with increased postoperative complications and higher costs. Many academic centers have a designated day for didactics that cause cases to start 1 hour later. The purpose of this study is to analyze the late-start effect of microvascular breast reconstructions on operative duration. A retrospective review was performed on all patients who underwent abdomina-based free flap breast reconstruction from 2007 to 2011 and analyzed by those who had surgery on late-start versus normal-start days. Patient demographics, average operative time, postoperative complications, and individual surgeon effects were analyzed. A Student t-test was used to compare operative times with statistical significance set at p < 0.05. A multivariate regression analysis was performed to control for potential confounders. A total of 272 patients underwent 461 free flap breast reconstructions. Twenty-one cases were performed on late-start days and 251 cases were performed on normal-start days. Patient demographics and complications were not statistically different between the groups. The average operative time for all reconstructions was 434.3 minutes. The average operative times were significantly longer for late-start days, 517.6 versus 427.3 minutes (p = 0.002). This was true for both unilateral and bilateral reconstructions (432.8 vs. 350.9 minutes, p = 0.05; 551.5 vs. 461.2 minutes, p = 0.007). There were no differences in perioperative complications and multivariate regression showed no statistically significant relationship of confounders to duration of surgery. Starting cases 1 hour later can increase operative times. Although outcomes were not affected, we recommend avoiding lengthy procedures on late-start days.


Synthesis, characterization and in vitro and in vivo anticancer activity of Pt(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)].
This report describes the synthesis, characterization and biological activity of a series of platinum(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] (Pt56MeSS) with non-bioactive, lipophilic and bioactive axial ligands. In an attempt to explore the anticancer activity potential of the Pt(iv) derivatives, 2D and 3D cytotoxic screening and a preliminary in vivo study were performed. The average IC50 values of the platinum(iv) derivatives ranged from 1.26 to 5.39 μM, compared with 1.24 μM for Pt56MeSS, suggesting that the axial ligands have a relatively minor effect on the potency of the compounds. Preliminary in vivo studies indicate that the platinum(iv) derivatives of Pt56MeSS are active in vivo and can reduce the tumor to a similar extent to cisplatin.


Fatigue rating scales: an empirical comparison.
There has been limited research comparing the efficacy of different fatigue rating scales for use with individuals with chronic fatigue syndrome (CFS). This investigation explored relationships between two commonly-used fatigue rating scales in CFS research, the Fatigue Scale and the Fatigue Severity Scale. Theoretically, these scales have been described as measuring different aspects of the fatigue construct. The Fatigue Scale was developed as a measure of the severity of specific fatigue-related symptoms, while the Fatigue Severity Scale was designed to assess functional outcomes related to fatigue. Associations of these scales with the eight definitional symptoms of CFS and with eight domains of functional disability were examined separately in: (1) an overall sample of individuals with a wide range of fatigue severity and symptomatology; (2) a subsample of individuals with CFS-like symptomatology, and, (3) a subsample of healthy controls. Findings revealed that both scales are appropriate and useful measures of fatigue-related symptomatology and disability within a general population of individuals with varying levels of fatigue. However, the Fatigue Severity Scale appears to represent a more accurate and comprehensive measure of fatigue-related severity, symptomatology, and functional disability for individuals with CFS-like symptomatology.


Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk.
To develop a practical thyroid imaging reporting and data system (TIRADS) with which to categorize thyroid nodules and stratify their malignant risk. The institutional review board approved this retrospective study, and the requirement to obtain informed consent for the review of images and records was waived. From May to December 2008, ultrasonographically (US)-guided fine-needle aspiration biopsy (FNAB) was performed in 3674 focal thyroid nodules in 3414 consecutive patients. The study included the 1658 thyroid nodules (≥1 cm in maximum diameter at US) in 1638 patients (1373 women, 265 men) for which pathologic diagnosis or follow-up findings were available. Univariate and multivariate analyses with generalized estimating equations were performed to investigate the relationship between suspicious US features and thyroid cancer. A score for each significant factor was assigned and multiplied by the β coefficient obtained for each significant factor from multivariate logistic regression analysis. Scores for each significant factor were then added, resulting in an equation that fitted the probability of malignancy in thyroid nodules. The authors evaluated the fitted probability by using a regression equation; the risk of malignancy was determined according to the number of suspicious US features. The following US features showed a significant association with malignancy: solid component, hypoechogenicity, marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. As the number of suspicious US features increased, the fitted probability and risk of malignancy also increased. Positive predictive values according to the number of suspicious US features were significantly different (P < .001). Risk stratification of thyroid malignancy by using the number of suspicious US features allows for a practical and convenient TIRADS.


Tamoxifen and TRAIL synergistically induce apoptosis in breast cancer cells.
Tamoxifen (TAM), is widely used as a single agent in adjuvant treatment of breast cancer. Here, we investigated the effects of TAM in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in estrogen receptor-alpha (ER-alpha)-positive and -negative breast cancer cells. We showed that cotreatment with TAM and TRAIL synergistically induced apoptosis regardless of ER-alpha status. By contrast, cotreatment did not affect the viability of normal breast epithelial cells. Cotreatment with TAM and TRAIL in breast cancer cells decreased the levels of antiapoptotic proteins including FLIPs and Bcl-2, and enhanced the levels of proapoptotic proteins such as FADD, caspase 8, tBid, Bax and caspase 9. Furthermore, cotreatment-induced apoptosis was efficiently reduced by FADD- or Bid-siRNA, indicating the implication of both extrinsic and intrinsic pathways in synergistic apoptosis induction. Importantly, cotreatment totally arrested tumor growth in an ER-alpha-negative MDA-MB-231 tumor xenograft model. The abrogation of tumor growth correlated with enhanced apoptosis in tumor tissues. Our findings raise the possibility to use TAM in combination with TRAIL for breast cancers, regardless of ER-alpha status.


Bodily changes and sensory sensitivity in complex regional pain syndrome and fibromyalgia.
Complex regional pain syndrome (CRPS) and fibromyalgia are chronic pain conditions of unexplained origins. In addition to symptoms in the diagnostic criteria, patients can report changes to vision and other sensations or bodily functions. It is unclear whether these are greater than would be expected due to normal ageing, living with chronic pain generally, or common comorbidities of chronic pain such as depression or anxiety. We administered an on-line survey evaluating the frequencies and types of self-reported somatic symptoms, bodily changes, and sensory sensitivity in respondents with CRPS (n = 390), fibromyalgia (n = 425), and both CRPS and fibromyalgia ("CRPS+fibromyalgia"; n = 88) compared to respondents with other chronic pain conditions (n = 331) and pain-free controls (n = 441). The survey assessed somatic symptoms (Patient Health Questionnaire-15), bodily changes, pain/discomfort/distress triggers, and pain intensifiers. We conducted analysis of covariance's with age, sex, Patient Health Questionnaire-9 (measuring depression), Generalized Anxiety Disorder-7, pain duration in years, hours of pain per day, and number of pain-related medical diagnoses as covariates. After controlling for covariates, respondents with CRPS and/or fibromyalgia reported more somatic symptoms, changes in movement and biological responses, pain/discomfort/distress triggers, and pain intensifiers than pain(-free) control groups. Fibromyalgia specifically related to changes in vision and hearing, urinary/intestinal function, and drinking and eating. Complex regional pain syndrome related to changes in hair, skin, and nails; and infection and healing. The CRPS+fibromyalgia group presented with features of both disorders with minimal additional stressors or symptoms over and above these. Our findings suggest that CRPS and fibromyalgia share underlying pathophysiologies, although specific mechanisms might be different.


Internal and cortical border-zone infarction: clinical and diffusion-weighted imaging features.
The pathogenesis of internal border-zone (IBZ) and cortical border-zone (CBZ) infarcts is unclear. Both types of infarct have been combined into a single group in most previous reports, which has produced conflicting results. We hypothesized that different pathogenic mechanisms underlie IBZ and CBZ infarcts. We reviewed 946 consecutive patients with ischemic stroke within the middle cerebral artery territory. IBZ and CBZ infarcts were selected based on diffusion-weighted imaging templates to identify vascular territories. Baseline patient characteristics, clinical courses, and neuroradiological features were compared between patients with IBZ and CBZ infarcts. We identified 45 IBZ and 75 CBZ infarct patients. Compared with the CBZ infarct patients, IBZ infarct patients had a higher degree of stenosis or occlusion in either the middle cerebral or internal carotid artery (P=0.008) and exhibited a rosary-like pattern of infarction more frequently (P<0.001). In contrast, concomitant small cortical infarcts were observed more frequently in CBZ infarct patients (P<0.001). Clinical deterioration during the first 7 days of admission and poor outcome after 3 months after stroke was more prevalent in IBZ infarct patients than in CBZ infarct patients (P=0.002 and P=0.003, respectively). IBZ infarcts are caused mainly by hemodynamic compromise, whereas embolic pathogenesis appears to contribute greatly to the genesis of CBZ infarcts. Patients with IBZ infarcts showed poor early and late clinical courses. Our findings suggest that different therapeutic approaches may be required to prevent early clinical deterioration in patients with different types of border-zone infarcts.


Thoughts on cataloging and classification in a small medical library.
This article is based on experience with small library collections. It is an effort to point out some of the problems in cataloging and classification, to arouse an interest in self-analysis on the part of the small library, and to offer some suggestions as to how the small institution can streamline techniques and economize on meager resources with no loss of value to the card catalog. It is recognized that the catalogs in many small libraries are unsuited for their tasks as a result of adhering to philosophies of larger institutions. The small institution has neither the need nor resources for such completeness in cataloging and classification. Deviation from standard rules is not advocated. However, consistency in treatment is advised and adherence in depth to standard rules is questioned.


Postoperative morbidity and mortality in relation to leukocyte counts and time to surgery after short-course preoperative radiotherapy for rectal cancer.
Preoperative radiotherapy for rectal cancer decreases local recurrence rates, but increases postoperative complications. Impaired postoperative leukocyte reaction after preoperative short-course radiotherapy has been reported. The aim was to assess postoperative morbidity and mortality in relation to leukocyte reaction and the time interval between radiotherapy and surgery. A retrospective analysis of patients included in the Stockholm I and II trials, randomising patients to surgery alone or to 5 x 5 Gy with immediate surgery, identified pre- and postoperative leukocyte values for 274 patients. In the surgery alone group (n=144), all but three patients (2%) reacted with leukocytosis (ratio post/preoperative >1.0) on day 1 and all but 9 (6%) on day 5. In the radiotherapy group (n=130), 40 (31%) became leukopenic (<4 x 10(9) cells/L) after radiotherapy, 29 (22%) reacted abnormally (leukopenia or ratio < or =1.0) on day 1 and 66 (51%) on day 5 (all p<0.001). Preoperative leukocyte counts did not influence postoperative morbidity, but a poor response on day 1 increased the risk of sepsis (p<0.05) and mortality (6/29 (21%) vs. 6/101 (6%), p<0.05). An interval of 10 days or more between the start of radiotherapy and surgery also had an impact on mortality; 6/17 (35%) vs. 6/113 (5%), p=0.001. In a logistic regression analysis, the time interval and age were independent predictors of mortality. Impaired postoperative leukocyte reaction is frequent after short-course radiotherapy and increases the risk of postoperative complications and death. A longer than recommended radiotherapy-surgery interval also appears to be detrimental for postoperative death, independently of leukocyte response.


Sleep quality and neural circuit function supporting emotion regulation.
Recent laboratory studies employing an extended sleep deprivation model have mapped sleep-related changes in behavior onto functional alterations in specific brain regions supporting emotion, suggesting possible biological mechanisms for an association between sleep difficulties and deficits in emotion regulation. However, it is not yet known if similar behavioral and neural changes are associated with the more modest variability in sleep observed in daily life. We examined relationships between sleep and neural circuitry of emotion using the Pittsburgh Sleep Quality Index and fMRI data from a widely used emotion regulation task focusing on cognitive reappraisal of negative emotional stimuli in an unselected sample of 97 adult volunteers (48 women; mean age 42.78±7.37 years, range 30-54 years old). Emotion regulation was associated with greater activation in clusters located in the dorsomedial prefrontal cortex (dmPFC), left dorsolateral prefrontal cortex (dlPFC), and inferior parietal cortex. Only one subscale from the Pittsburgh Sleep Quality Index, use of sleep medications, was related to BOLD responses in the dmPFC and dlPFC during cognitive reappraisal. Use of sleep medications predicted lesser BOLD responses during reappraisal, but other aspects of sleep, including sleep duration and subjective sleep quality, were not related to neural activation in this paradigm. The relatively modest variability in sleep that is common in the general community is unlikely to cause significant disruption in neural circuits supporting reactivity or regulation by cognitive reappraisal of negative emotion. Use of sleep medication however, may influence emotion regulation circuitry, but additional studies are necessary to determine if such use plays a causal role in altering emotional responses.


Free tyrosine and tyrosine-rich peptide-dependent superoxide generation catalyzed by a copper-binding, threonine-rich neurotoxic peptide derived from prion protein.
Previously, generation of superoxide anion (O(2)(*-)) catalyzed by Cu-binding peptides derived from human prion protein (model sequence for helical Cu-binding motif VNITKQHTVTTTT was most active) in the presence of catecholamines and related aromatic monoamines such as phenylethylamine and tyramine, has been reported [Kawano, T., Int J Biol Sci 2007; 3: 57-63]. The peptide sequence (corresponding to helix 2) tested here is known as threonine-rich neurotoxic peptide. In the present article, the redox behaviors of aromatic monoamines, 20 amino acids and prion-derived tyrosine-rich peptide sequences were compared as putative targets of the oxidative reactions mediated with the threonine-rich prion-peptide. For detection of O(2)(*-), an O(2)(*-)-specific chemiluminescence probe, Cypridina luciferin analog was used. We found that an aromatic amino acid, tyrosine (structurally similar to tyramine) behaves as one of the best substrates for the O(2)(*-) generating reaction (conversion from hydrogen peroxide) catalyzed by Cu-bound prion helical peptide. Data suggested that phenolic moiety is required to be an active substrate while the presence of neither carboxyl group nor amino group was necessarily required. In addition to the action of free tyrosine, effect of two tyrosine-rich peptide sequences YYR and DYEDRYYRENMHR found in human prion corresponding to the tyrosine-rich region was tested as putative substrates for the threonine-rich neurotoxic peptide. YYR motif (found twice in the Y-rich region) showed 2- to 3-fold higher activity compared to free tyrosine. Comparison of Y-rich sequence consisted of 13 amino acids and its Y-to-F substitution mutant sequence revealed that the tyrosine-residues on Y-rich peptide derived from prion may contribute to the higher production of O(2)(*-). These data suggest that the tyrosine residues on prion molecules could be additional targets of the prion-mediated reactions through intra- or inter-molecular interactions. Lastly, possible mechanism of O(2)(*-) generation and the impacts of such self-redox events on the conformational changes in prion are discussed.


Distribution of Eurasian otter biliary parasites, Pseudamphistomum truncatum and Metorchis albidus (Family Opisthorchiidae), in England and Wales.
Gall bladders from 273 otter carcasses, collected throughout England and Wales, were screened to assess the status of gall bladder parasites in the Eurasian otter, Lutra lutra. The digenean Pseudamphistomum truncatum had previously been found in UK otters collected between 2000 and 2007. The parasite was established in Somerset and Dorset but its distribution elsewhere in the UK was largely unknown. In the current study, P. truncatum was also found to be abundant in south Wales, with occasional cases elsewhere, but appears to be absent from the north of England. Overall, 11.7% of otters were infected with 1-238 P. truncatum. A second digenean, Metorchis albidus, previously unreported in British otters, was found in the biliary system of 6.6% of otters. M. albidus appears well established in Suffolk, Norfolk and north Essex but was recorded elsewhere rarely. Both parasites are associated with pathological damage to the otter gall bladder. The recent discovery of these two non-native parasites provides a unique opportunity to assess their impact on native British fauna.


Palms, peccaries and perturbations: widespread effects of small-scale disturbance in tropical forests.
Disturbance is an important process structuring ecosystems worldwide and has long been thought to be a significant driver of diversity and dynamics. In forests, most studies of disturbance have focused on large-scale disturbance such as hurricanes or tree-falls. However, smaller sub-canopy disturbances could also have significant impacts on community structure. One such sub-canopy disturbance in tropical forests is abscising leaves of large arborescent palm (Arececeae) trees. These leaves can weigh up to 15 kg and cause physical damage and mortality to juvenile plants. Previous studies examining this question suffered from the use of static data at small spatial scales. Here we use data from a large permanent forest plot combined with dynamic data on the survival and growth of > 66,000 individuals over a seven-year period to address whether falling palm fronds do impact neighboring seedling and sapling communities, or whether there is an interaction between the palms and peccaries rooting for fallen palm fruit in the same area as falling leaves. We tested the wider generalisation of these hypotheses by comparing seedling and sapling survival under fruiting and non-fruiting trees in another family, the Myristicaceae. We found a spatially-restricted but significant effect of large arborescent fruiting palms on the spatial structure, population dynamics and species diversity of neighbouring sapling and seedling communities. However, these effects were not found around slightly smaller non-fruiting palm trees, suggesting it is seed predators such as peccaries rather than falling leaves that impact on the communities around palm trees. Conversely, this hypothesis was not supported in data from other edible species, such as those in the family Myristicaceae. Given the abundance of arborescent palm trees in Amazonian forests, it is reasonable to conclude that their presence does have a significant, if spatially-restricted, impact on juvenile plants, most likely on the survival and growth of seedlings and saplings damaged by foraging peccaries. Given the abundance of fruit produced by each palm, the widespread effects of these small-scale disturbances appear, over long time-scales, to cause directional changes in community structure at larger scales.


Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response.
We have studied the response to intravenous immunoglobulins (IVIg) by a transcriptomic approach in 11 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients (CIDP duration = 6 [0.83-6.5] years). RNA was extracted from cells in whole blood collected before and 3 weeks after IVIg treatment, and hybridized on Illumina chips. After RNA quality controls, gene expression was analyzed using statistical tests fitted for microarrays (R software, limma package), and a pathway analysis was performed using DAVID software. We identified 52 genes with expression that varied significantly after IVIg (fold change [FC] > 1.2, P < 0.001, false discovery rate [FDR] <0.05). Among these 52 genes, 7 were related to immunity, 3 were related to the tumor necrosis factor (TNF)-α receptor 1 (TNFR1) pathway (inhibitor of caspase-activated DNase (ICAD): FC = 1.8, P = 1.7E-7, FDR = 0.004; p21 protein-activated kinase 2 [PAK2]: FC = 1.66, P = 2.6E-5, FDR = 0.03; TNF-α-induced protein 8-like protein 1 [TNFAIP8L1]: P = 1.00E-05, FDR = 0.026), and 2 were related to Toll-like receptors (TLRs), especially TLRs 7 and 9, and were implicated in autoimmunity. These genes were UNC93B1 (FC = 1.6, P = 2E-5, FDR = 0.03), which transports TLRs 7 and 9 to the endolysosomes, and RNF216 (FC = 1.5, P = 1E-05, FDR = 0.03), which promotes TLR 9 degradation. Pathway analysis showed that the TNFR1 pathway was significantly lessened by IVIg (enrichment score = 24, Fischer exact test = 0.003). TNF-α gene expression was higher in responder patients than in nonresponders; however, it decreased after IVIg in responders (P = 0.04), but remained stable in nonresponders. Our data suggest the actions of IVIg on the TNFR1 pathway and an original mechanism involving innate immunity through TLRs in CIDP pathophysiology and the response to IVIg. We conclude that responder patients have stronger inflammatory activity that is lessened by IVIg.


Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas.
Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats). Organotypic cultures of rat primary NFPAs were incubated with NVP-BEZ235 and assessed for cell viability, proliferation, apoptosis, and PI3K/mTOR inhibition. NVP-BEZ235, or placebo, was administered to MENX rats and tumor response was monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tumor tissues were investigated for cell proliferation, apoptosis, and PI3K/mTOR inhibition. Genes mediating the cytotoxic activity of NVP-BEZ235 were identified by gene-expression profiling. Among them, Defb1, encoding beta-defensin 1, was further studied for its role in pituitary cells and in human pancreatic neuroendocrine tumor (NET) cells. NVP-BEZ235 showed antiproliferative and pro-cell death activities against NFPAs both in vitro and in vivo, and the response to the drug correlated with inhibition of the PI3K pathway. DW-MRI identified early functional changes (decreased cellularity) in the adenomas before their size was affected and emerged as a useful modality to assess therapy response. The cytotoxic effect of PI3K/mTOR blockade in NFPA was mediated by several genes, including Defb1. NVP-BEZ235 treatment induced Defb1 expression in NFPAs in vitro and in vivo, and in pancreatic NET cells. High Defb1 levels sensitized NET cells to PI3K/mTOR inhibition. Our findings provide rationale for clinical investigation of PI3K/mTOR inhibition in NFPAs and identify novel effectors of PI3K-mediated neuroendocrine cell survival.


Discharge medications among ischemic stroke survivors.
The aim of this study was to analyze the types and cost of medications prescribed at discharge for ischemic stroke survivors. This is a descriptive study of medications prescribed for ischemic stroke survivors admitted to Al-watani hospital during a 6-month period. A total of 95 consecutive stroke patients were included in the study period; 78 (82.1%) survivors were having ischemic stroke subtype and were designated the study group. The average age of the survivors was 66.9 +/- 12.7 years. Survivors had prevalent risk factors such as diabetes mellitus (70%), hypertension (68%), and ischemic heart disease (34.6%). On average, survivors experienced a minimum of 0.73 complications (range 0-3) with the most common being infections (n = 35, 44.8%). Forty-two per cent of the ischemic stroke survivors were taking antiplatelet drugs prior to the current attack. At discharge, ischemic stroke survivors were prescribed an average of 4.9 medications from 4.3 different drug classes. All ischemic stroke survivors were prescribed antiplatelet therapy at discharge. Aspirin monotherapy was prescribed for 61 survivors while the combination of aspirin/clopidogrel antiplatelet therapy was prescribed for 17 survivors. The average monthly cost for prophylactic therapy and for medications used to treat post-stroke complication was approximately 52 USD per survivor. Most of the patients in the study group were having the traditional risk factors for ischemic stroke and were suffering form typical post-stroke complications. Lack of medical insurance will impose a heavy financial burden on stroke survivors in Palestine.


Earliest infections predict the age distribution of seasonal influenza A cases.
Seasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza.


Asymmetric femtosecond laser ablation of silicon surface governed by the evolution of surface nanostructures.
The femtosecond laser ablation of silicon surface near the ablation threshold was investigated and the preferential ablation along different directions was observed in different stages. It was found that the ripples formed in the initial stage facilitate the ablation along the direction perpendicular to the ripples, leading to the formation of an elliptical ablation area. With increasing length and depth of the ripples, however, nanohole arrays formed in the ripples will modify the distribution of electric field which benefits the ablation along the direction parallel to the ripples. Consequently, the ablation area is gradually changed to a circular one after irradiating sufficient number of pulses.


Body weight and longevity. A reassessment.
Conflicting results have been reported concerning the association between body weight and longevity. The shape of the curve relating weight to all-cause mortality has been variously described as linear, J-shaped, and even U-shaped. To assess the validity of the evidence for optimal weight recommendations, we examined the 25 major prospective studies on the subject. Each study had at least one of three major biases: failure to control for cigarette smoking, inappropriate control of biologic effects of obesity, such as hypertension and hyperglycemia, and failure to control for weight loss due to subclinical disease. The presence of these biases leads to a systematic underestimate of the impact of obesity on premature mortality. Although these biases preclude a valid assessment of optimal weight from existing data, available evidence suggests that minimum mortality occurs at relative weights at least 10% below the US average.


New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients.
To develop a novel molecular panel of markers to detect breast cancer (BC) disseminated malignant cells in ovarian tissue, and to improve the safety of ovarian tissue transplantation. Experimental study. University hospital. Ten ovarian biopsies from healthy patients, 13 biopsies with diagnosed BC metastasis, and 4 biopsies from primary BC tumor for designing a diagnostic panel of BC cell contamination; 60 ovarian biopsies from BC patients undergoing fertility preservation for validating the panel. Female nude mice. A novel panel for BC malignant cell detection by reverse-transcription polymerase chain reaction (RT-PCR), inmmunohistochemical analysis, in vitro invasion assay and xenotransplantation assayed in ovarian tissue from BC patients. Expression of GCDFP15, MGB1, SBEM, MUC1, WT-1, and NY-BR-01, selected as markers, assessed by quantitative RT-PCR in samples with confirmed BC metastasis. The most sensitive markers were confirmed by immunohistochemistry, and tested in vitro and in vivo. GCDFP15, MGB1, and SBEM were the most sensitive and specific markers to detect BC metastatic cells when at least one was expressed by quantitative RT-PCR. The panel was validated in 60 patients and confirmed in an in vitro invasion assay, where no invasive cells were observed. Samples negative for BC cells cannot develop disease when xenografted. GCDFP15, MGB1, and SBEM were the most sensitive molecules to create a diagnostic panel for BC malignant cell contamination, which may make ovarian tissue cryopreservation and transplantation a safe technique for fertility preservation in BC patients.


Optimization of the atrioventricular delay during cardiac resynchronization therapy using a device for non-invasive measurement of cardiac index at rest and during exercise.
It is not clear whether cardiac resynchronization therapy (CRT) should only be optimized at rest or whether it is necessary to perform CRT optimization during exercise. Our study aims to answer this question by using an inert gas rebreathing method (Innocor®). Twenty-seven patients with congestive heart failure and implanted CRT devices were included in the study. The aetiology of the heart failure was ischaemic in nine (33%) patients. Patients had low left ventricular ejection fraction (29 ± 8%) and enlarged LV end-diastolic diameters (63 ± 7 mm). Atrioventricular delay (AVD) was optimized at rest according to cardiac index (CI), measured by inert gas rebreathing (Innocor®). Thereafter, patients performed standardized, steady-state bicycle exercise at 30 W in sitting body position. Three AVDs were tested during exercise in a random sequence: optimized resting AVD (AVD(opt)) according to baseline measurement; AVD(opt) - 30 ms; and AVD(opt) + 30 ms. Cardiac index was measured in each AVD by inert gas rebreathing. Cardiac index increased significantly during exercise. However, neither AVD(opt) shortening nor prolongation during exercise had significant effect on CI (shortening of AVD(opt) - 30 ms was accompanied by a reduction of CI of 4.8%, prolongation of AVD(opt) + 30 ms was accompanied by a reduction of CI of 7.7%). Shortening or lengthening of the AVD during exercise has no impact on CI in CRT patients. On the basis of our results, we conclude that in CRT patients the AVD should be programmed, fixed even during exercise.


Does blood pressure variability modulate cardiovascular risk?
Exactly how hypertension causes end organ damage and vascular events is poorly understood. Yet the concept that underlying "usual" blood pressure (BP) accounts for all BP-related risk of vascular events and for the benefits of BP-lowering drugs has come to underpin clinical guidelines on the diagnosis and treatment of hypertension. This article reviews evidence that variability in BP also predicts risk of stroke and other vascular events independently of mean BP and evidence that drug-class effects on variability in BP explain differences in the effectiveness of BP-lowering drugs in preventing stroke.


Key Players in Choline Metabolic Reprograming in Triple-Negative Breast Cancer.
Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. 1H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment. Several studies have shown an altered phosphatidylcholine (PtdCho) metabolism in TNBCs, both in patients and in experimental models. Upregulation of choline kinase-alpha, an enzyme of the Kennedy pathway that phosphorylates free choline (Cho) to phosphocholine (PCho), is a major contributor to the increased PCho content detected in TNBCs. Phospholipase-mediated PtdCho headgroup hydrolysis also contributes to the build-up of a PCho pool in TNBC cells. The oncogene-driven PtdCho cycle appears to be fine tuned in TNBC cells in at least three ways: by modulating the choline import, by regulating the activity or expression of specific metabolic enzymes, and by contributing to the rewiring of the entire metabolic network. Thus, only by thoroughly dissecting these mechanisms, it will be possible to effectively translate this basic knowledge into further development and implementation of Cho-based imaging techniques and novel classes of therapeutics.


Top management leadership style and quality of care in nursing homes.
The purpose of this study was to examine the association of Nursing Home Administrator (NHA) leadership style and Director of Nursing (DON) leadership style with quality of care. Leaders were categorized into 4 groups: consensus managers, consultative autocrats, shareholder managers, or autocrats. This leadership style assessment came from primary data collected from approximately 4,000 NHAs and DONs that was linked to quality information (i.e., Nursing Home Compare Quality Measures and 5-Star rating scores) and nursing home information (i.e., Online Survey, Certification, And Reporting data). A consensus manager leadership style has a strong association with better quality. Top managers using this style solicit and act upon input from their employees. For NHAs exhibiting this leadership style, the coefficients on 5 of the 7 quality indicators are statistically significant, and all 7 are significant when the DON exhibits this style. When the NHA and DON both have a consensus manager leadership style, 6 of the 7 quality indicator coefficients are significantly associated with better quality. The findings indicate that NHA and DON leadership style is associated with quality of care. Leadership strategies are amenable to change; thus, the findings of this study may be used to develop policies for promoting more effective leadership in nursing homes.


Electromagnetic fields and optomechanics in cancer diagnostics and treatment.
In this paper, we discuss biological effects of electromagnetic (EM) fields in the context of cancer biology. In particular, we review the nanomechanical properties of microtubules (MTs), the latter being one of the most successful targets for cancer therapy. We propose an investigation on the coupling of electromagnetic radiation to mechanical vibrations of MTs as an important basis for biological and medical applications. In our opinion, optomechanical methods can accurately monitor and control the mechanical properties of isolated MTs in a liquid environment. Consequently, studying nanomechanical properties of MTs may give useful information for future applications to diagnostic and therapeutic technologies involving non-invasive externally applied physical fields. For example, electromagnetic fields or high intensity ultrasound can be used therapeutically avoiding harmful side effects of chemotherapeutic agents or classical radiation therapy.


Novel ADAM9 homozygous mutation in a consanguineous Egyptian family with severe cone-rod dystrophy and cataract.
To genetically and phenotypically describe a new ADAM9 homozygous mutation in a consanguineous family from Egypt with autosomal recessive cone-rod dystrophy (arCRD), anterior polar and posterior subcapsular cataract. The parents and their six children were included. They underwent a complete ophthalmic examination with fundus photography and optical coherence tomography (OCT). DNA was extracted from peripheral blood from all family members. Screening for mutations in genes known to be implicated in retinal disorders was done with the IROme, an in-solution enrichment array, followed by high-throughput sequencing. Validation of the results was done by bidirectional Sanger sequencing of ADAM9 exon 14, including exon-intron junctions. Screening of normal controls was done by denaturing high-performance liquid chromatography. arCRD was diagnosed in the mother and two of her children. Bilateral anterior polar and posterior subcapsular cataract was observed in the mother and bilateral dot cataract was diagnosed in three of the four children not affected with arCRD, one of whom also had glaucoma. The characteristics of the arCRD were childhood-onset visual impairment, reorganisation of the retinal pigment epithelium with mid-periphery greyish-white discolouration, attenuated retinal vasculatur and optic disc pallor. A coloboma-like macular lesion was observed in one of the arCRD-affected children. IROme analysis identified a c.1396-2A>G homozygous mutation in the splice acceptor site of intron 13 of ADAM9. This mutation was homozygous in the two children affected by arCRD and in their affected mother. This mutation was heterozygous in the unaffected father and the four unaffected children. We identified a novel autosomal recessive ADAM9 mutation causing arCRD in a consanguineous Egyptian family. The percentage of arCRD cases caused by mutation in ADAM9 remains to be determined. Few families are reported in the literature to date; hence extensive clinical descriptions of families with ADAM9 mutations are of significant importance.


Governance of dual-use research: an ethical dilemma.
Scenarios where the results of well-intentioned scientific research can be used for both good and harmful purposes give rise to what is now widely known as the 'dual-use dilemma'. There has been growing debate about the dual-use nature of life science research with implications for making biological weapons. This paper reviews several controversial publications that have been the focus of debates about dual-use life science research and critically examines relevant policy developments, particularly in the United States of America. Though the dual-use dilemma is inherently ethical in nature, the majority of debates about dual-use research have primarily involved science and security experts rather than ethicists. It is important that there is more ethical input into debates about the governance of dual-use research.


Ovarian cancer HO-8910 cell apoptosis induced by crocin in vitro.
The effect and mechanism of ovarian cancer HO-8910 cell apoptosis induced by crocin.MTT assay was performed to detect the inhibitory action of crocin on the proliferation of HO-8910 cells. Flow cytometry was used to test the cell cycle distribution and apoptosis rate of ovarian cancer HO-8910 cells. Western blot analysis was utilized to measure the levels of apoptotic proteins such as p53, Fas/APO-1, and Caspase-3. MTT analysis revealed that crocin significantly inhibited the growth of HO-8910 cells. Additionally, flow cytometry illustrated that crocin raised the proportion of HO-8910 cells in the G0/G1 phase and increased their apoptosis rate. Furthermore, Western blot analysis revealed that crocin up-regulated the expression of p53, Fas/APO-1, and Caspase-3. The results of this study showed that crocin can significantly inhibit the growth of HO-8910 cells and arrest them in the G0/G1 phase. Crocin can also promote ovarian cancer HO-8910 cell apoptosis, most likely by increasing p53 and Fas/APO-1 expression, and then activating the apoptotic pathway regulated by Caspase-3.


Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus.
Belimumab is the first biologic drug approved for Systemic Lupus Erythematosus (SLE). Here, we aimed to investigate the effects of belimumab on clinical and serologic outcomes, and sought to identify predictors of treatment response in three Swedish real-life settings. Fifty-eight patients were enrolled at initiation of belimumab and followed longitudinally for up to 53months. Surveillance outcomes included the SLE Disease Activity Index 2000 (SLEDAI-2K), 100mm Visual Analogue Scales for Physician's Global Assessment (PGA), fatigue, pain and general health, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Assessment of treatment response included the SLE responder index (SRI). B lymphocyte stimulator (BLyS) levels were determined using ELISA. SLEDAI-2K (median baseline score: 8.0; IQR: 4.0-13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health (p<0.0001 for all). SDI scores remained stable (p=0.08). Patients with baseline SDI scores >1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208-0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025-0.427). In contrast, baseline BLyS levels ≥1.2ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222-5.387). Disease activity and corticosteroid usage decreased, patient-reported outcomes improved, and no significant organ damage was accrued during follow-up. Smoking and organ damage predicted reduced treatment efficacy. These findings might contribute to a better selection of patients who are likely to benefit from belimumab.


Intestinal spirochaetes colonizing aborigines from communities in the remote north of Western Australia.
Intestinal spirochaetal bacteria were isolated from 59 of 181 (32.6%) faecal samples obtained from Aboriginal children and a few adults living in communities in the Kimberley region in the north of Western Australia. Colonization was more common in young Aborigines between 2 and 18 years of age than it was in adults, or in babies and children less than 2 years of age. Three of 22 Aboriginal children who were sampled on two consecutive years were colonized on both occasions. None of four other children were found to be consistently colonized with the bacteria when sampled on three sequential years, but three were positive on two consecutive visits and the other child was positive on the first and third sampling. Most Aboriginal children had abnormal or watery stools, and both abnormal and watery stool samples were significantly more likely to contain spirochaetes than were normal samples. However, it was not possible to prove that the spirochaetes were the cause of the diarrhoea. In contrast, spirochaetes were only recovered from 8 of 695 (1.2%) faecal samples that were obtained from other mainly non-Aboriginal children and adults in Western Australia or the Northern Territory of Australia, even though most of these individuals were suffering from gastrointestinal disturbances.


Narrowed expectancies under degraded speech: revisiting the N400.
Under adverse listening conditions, speech comprehension profits from the expectancies that listeners derive from the semantic context. However, the neurocognitive mechanisms of this semantic benefit are unclear: How are expectancies formed from context and adjusted as a sentence unfolds over time under various degrees of acoustic degradation? In an EEG study, we modified auditory signal degradation by applying noise-vocoding (severely degraded: four-band, moderately degraded: eight-band, and clear speech). Orthogonal to that, we manipulated the extent of expectancy: strong or weak semantic context (±con) and context-based typicality of the sentence-last word (high or low: ±typ). This allowed calculation of two distinct effects of expectancy on the N400 component of the evoked potential. The sentence-final N400 effect was taken as an index of the neural effort of automatic word-into-context integration; it varied in peak amplitude and latency with signal degradation and was not reliably observed in response to severely degraded speech. Under clear speech conditions in a strong context, typical and untypical sentence completions seemed to fulfill the neural prediction, as indicated by N400 reductions. In response to moderately degraded signal quality, however, the formed expectancies appeared more specific: Only typical (+con +typ), but not the less typical (+con -typ) context-word combinations led to a decrease in the N400 amplitude. The results show that adverse listening "narrows," rather than broadens, the expectancies about the perceived speech signal: limiting the perceptual evidence forces the neural system to rely on signal-driven expectancies, rather than more abstract expectancies, while a sentence unfolds over time.


MEMS micromirror characterization in space environments.
This paper describes MEMS micromirror characterization in space environments associated with our space applications in earth observation from the International Space Station and earth's orbit satellite. The performance of the micromirror was tested for shock and vibration, stiction, outgassing from depressurization and heating, and electrostatic charging effects. We demonstrated that there is no degradation of the micromirror performance after the space environment tests. A test bed instrument equipped with the micromirrors was delivered and tested in the ISS. The results demonstrate that the proposed micromirrors are suitable for optical space systems.


Enrichment of Human CCR6+ Regulatory T Cells with Superior Suppressive Activity in Oral Cancer.
Human oral squamous cell carcinoma (OSCC) constitutes an inflammatory microenvironment enriched with chemokines such as CCL20, which promote cancer cell invasion and tumor progression. We found that in OSCC there is a correlation between the expression of CCL20 and FOXP3 mRNA. Therefore, we hypothesized that OSCC may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. Interestingly, most (∼60%) peripheral blood Treg cells express CCR6, and CCR6+ Treg cells exhibit an activated effector/memory phenotype. In contrast, a significant portion (>30%) of CCR6- Treg cells were found to be CD45RA+ naive Treg cells. Compared to CCR6- naive or memory Treg cells, CCR6+ Treg cells exhibit stronger suppressive activity and display higher FOXP3 expression along with lower methylation at the Treg-specific demethylated region of the FOXP3 gene. This predominance of CCR6+ Treg cells was also found in the draining lymph nodes and tumor-infiltrating lymphocytes of OSCC patients with early or late clinical staging. Moreover, CCR6+ Treg cells isolated from tumor-infiltrating lymphocytes or draining lymph nodes maintained similar phenotypic and suppressive characteristics ex vivo as did their counterparts isolated from peripheral blood. These results suggest that CCR6 marks activated effector or memory Treg phenotypes with superior suppressive activity in humans.


STRUCTURE AND DEVELOPMENT OF VIRUSES OBSERVED IN THE ELECTRON MICROSCOPE : IV. VIRUSES OF THE RI-APC GROUP.
Representative viruses of the RI-APC group were observed with the electron microscope in thin sections of infected HeLa cells. The viral particles varied in density, were approximately 60 mmicro in diameter and had a center to center spacing when close packed of about 65 mmicro. Many of the less dense particles exhibited an internal body averaging 24 mmicro in diameter. It was suggested that within the nucleus the virus differentiated from dense granular and reticular material and formed crystals. Disintegration of the crystals and disruption of the nuclear membrane with release of virus into the cytoplasm appeared to occur at any stage. No evidence to suggest development of the virus in the cytoplasm was obtained. It was possible to deduce the structure of the viral crystal from the electron micrographs. The viral particles are packed in a cubic body-centered lattice. Correlative histochemical observations in the light microscope which are now in progress revealed that the crystals and non-crystalline aggregates of virus were strongly Feulgen-positive.


Toggenburg Orbivirus, a new bluetongue virus: initial detection, first observations in field and experimental infection of goats and sheep.
A novel bluetongue virus termed "Toggenburg Orbivirus" (TOV) was detected in two Swiss goat flocks. This orbivirus was characterized by sequencing of 7 of its 10 viral genome segments. The sequencing data revealed that this virus is likely to represent a new serotype of bluetongue virus [Hofmann, M.A., Renzullo, S., Mader, M., Chaignat, V., Worwa, G., Thuer, B., 2008b. Genetic characterization of Toggenburg Orbivirus (TOV) as a tentative 25th serotype of bluetongue virus, detected in goats from Switzerland. Emerg. Infect. Dis. 14, 1855-1861]. In the field, no clinical signs were observed in TOV-infected adult goats; however, several stillborn and weak born kids were reported. Although born during a period of extremely low vector activity, one of these kids was found to be antibody and viral genome positive and died 3.5 weeks postpartum. Experimental infection of goats and sheep, using TOV-positive field blood samples, was performed to assess the pathogenicity of this virus. Goats did not show any clinical or pathological signs, whereas in sheep mild bluetongue-like clinical signs were observed. Necropsy of sheep demonstrated bluetongue-typical hemorrhages in the wall of the pulmonary artery. Viral RNA was detected in organs, e.g. spleen, palatine tonsils, lung and several lymph nodes of three experimentally infected animals. Unlike other bluetongue virus serotypes, it was not possible to propagate the virus, either from naturally or experimentally infected animals in any of the tested mammalian or insect cell lines or in embryonated chicken eggs. In small ruminants, TOV leads to mild bluetongue-like symptoms. Further investigations about prevalence of this virus are needed to increase the knowledge on its epidemiology.


A suggested bisphenol A metabolite (MBP) interfered with reproductive organ development in the chicken embryo while a human-relevant mixture of phthalate monoesters had no such effects.
Bisphenol A (BPA) and phthalate diesters are ubiquitous environmental contaminants. While these compounds have been reported as reproductive toxicants, their effects may partially be attributed to metabolites. The aim of this study was to examine reproductive organ development in chicken embryos exposed to the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP; 100 µg/g egg) or a human-relevant mixture of 4 phthalate monoesters (85 µg/g egg). The mixture was designed within the EU project EDC-MixRisk based upon a negative association with anogenital distance in boys at 21 months of age in a Swedish pregnancy cohort. Chicken embryos were exposed in ovo from an initial stage of gonad differentiation (embryonic day 4) and dissected two days prior to anticipated hatching (embryonic day 19). No discernible effects were noted on reproductive organs in embryos exposed to the mixture. MBP-treated males exhibited retention of Müllerian ducts and feminization of the left testicle, while MBP-administered females displayed a diminished the left ovary. In the left testicle of MBP-treated males, mRNA expression of female-associated genes was upregulated while the testicular marker gene SOX9 was downregulated, corroborating a feminizing effect by MBP. Our results demonstrate that MBP, but not the phthalate monoester mixture, disrupts both male and female reproductive organ development in an avian embryo model.


ARF1 regulates Nef-induced CD4 degradation.
The HIV Nef protein downregulates CD4 through sequential connection with clathrin-coated pits and the COP1 coatomer, resulting in accelerated endocytosis and lysosomal targeting. Here we report that the small GTPase ARF1 controls the Nef-induced, COP-mediated late-endosomal targeting of CD4. We find that Nef binds ARF1 directly and can recruit the GTPase onto endosomal membranes. Furthermore, a complex comprising Nef, ARF1, and betaCOP can be immunoprecipitated from cells expressing the viral protein. Residues in a C-terminal loop of the viral protein facilitate both these interactions and the targeting of Nef and CD4 to acidic late endosomes, whereas other residues primarily involved in mediating CD4 endocytosis are dispensable for this process. Finally, a dominant-negative ARF1 mutant blocks the migration of the Nef-CD4 complex to lysosomes. Our results support a model in which ARF1 is the immediate downstream partner of Nef for CD4 lysosomal targeting.