Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of a Cytotoxic Enterotoxin in Aeromonas-Mediated Infections: Development of Transposon and Isogenic Mutants

ABSTRACT Transposon and marker exchange mutagenesis were used to evaluate the role of Aeromonas cytotoxic enterotoxin (Act) in the pathogenesis of diarrheal diseases and deep wound infections. The transposon mutants were generated by random insertion of Tn5-751 in the chromosomal DNA of a diarrheal isolate SSU of Aeromonas hydrophila. Some of the transposon mutants had dramatically reduced hemolytic and cytotoxic activities, and such mutants exhibited reduced virulence in mice compared to wild-typeAeromonas when injected intraperitoneally (i.p.). Southern blot data indicated that transposition in these mutants did not occur within the cytotoxic enterotoxin gene (act). The transcription of the act gene was affected drastically in the transposon mutants, as revealed by Northern blot analysis. The altered virulence of these transposon mutants was confirmed by developing isogenic mutants of the wild-type Aeromonas by using a suicide vector. In these mutants, the truncated actgene was integrated in place of a functionally active actgene. The culture filtrates from isogenic mutants were devoid of hemolytic, cytotoxic, and enterotoxic activities associated with Act. These filtrates caused no damage to mouse small intestinal epithelium, as determined by electron microscopy, whereas culture filtrates from wild-type Aeromonas caused complete destruction of the microvilli. The 50% lethal dose of these mutants in mice was 1.0 × 108 when injected i.p., compared to 3.0 × 105 for the wild-type Aeromonas. Reintegration of the native act gene in place of the truncated toxin gene in isogenic mutants resulted in complete restoration of Act’s biological activity and virulence in mice. The animals injected with a sublethal dose of wild-type Aeromonas or the revertant, but not the isogenic mutant, had circulating toxin-specific neutralizing antibodies. Taken together, these studies clearly established a role for Act in the pathogenesis of Aeromonas-mediated infections.
A 15.5-year follow-up study of stroke in a Japanese provincial city. The Shibata Study.

BACKGROUND AND PURPOSE Change toward Western lifestyles, particularly during the high economic growth period (approximately 1960 to 1975), dynamically altered stroke frequency and the distribution of risk factors in the Japanese. We reexamined their association after this environmental change by a cohort study. METHODS The cohort (2302 subjects) comprised residents aged 40 years or older of the Akadani-Ijimino district in Shibata City, Niigata Prefecture, Japan, who were followed up from 1977 for 15.5 years. RESULTS Crude incidence rates per 1000 person-years for all strokes were 5.22 for men and 4.36 for women (3.02 and 2.18 for cerebral infarction, 0.65 and 1.06 for intracerebral hemorrhage, and 0.41 and 0.34 for subarachnoid hemorrhage, respectively). Multivariate analyses performed with the Cox proportional hazard model revealed these risk factors to be independently significant: for cerebral infarction in men, age, blood pressure, atrial fibrillation, albuminuria, funduscopic abnormality, and current smoking: for cerebral infarction in women, age, atrial fibrillation, and history of ischemic heart disease; for intracerebral hemorrhage in men, age and funduscopic abnormality; for intracerebral hemorrhage in women, age, blood pressure, and light physical activity; for all strokes in men, age, blood pressure, atrial fibrillation, albuminuria, funduscopic abnormality, current smoking, and heavy physical activity; and for all strokes in women, age, atrial fibrillation, and light physical activity. CONCLUSIONS Most traditional risk factors, including blood pressure and its related organ diseases, were confirmed, but serum total cholesterol had almost no effect. Physical activity had both negative and positive effects on stroke risk. In these findings, however, some differences related to sex were also observed.
Incidence of dementia: evidence for an effect modification by gender. The ILSA Study

ABSTRACT Background: Gender differences for incidence of dementia among elderly people have been usually investigated considering gender as a predictor and not as a stratification variable. Methods: Analyses were based on data collected by the Italian Longitudinal Study on Aging (ILSA), which enrolled 5,632 participants aged 65–84 years between 1992 and 2000. During a median follow-up of 7.8 years, there were 194 cases of incident dementia in the participants with complete data. Cox proportional hazard models for competing risks, stratified by sex, were defined to determine risk factors in relation to developing dementia. Results: The incidence rate of dementia increased from 5.57/1,000 person-years at 65–69 years of age to 30.06/1,000 person-years at 80–84 years. Cox proportional hazard models for competing risks of incidence of dementia and death revealed that, among men, significant risk factors were heart failure, Parkinson's disease, family history of dementia, mild depressive symptomatology and age, while triglycerides were associated with a lower risk of developing dementia. Significant risk factors in women were age, both mild and severe depressive symptomatology, glycemia ≥109 mg/dL, and a BMI < 24.1 kg/m2. Even as little as three years of schooling was found to be a significant protective factor against the incidence of dementia only for women. Conclusions: Our results suggest that there is an effect modification by gender in our study population in relation to the association between low education level, lipid profile, BMI, and glycemia and dementia.
In vitro endothelial cell damage is positively correlated with enhanced virulence and poor vancomycin responsiveness in experimental endocarditis due to methicillin‐resistant Staphylococcus aureus

The pathogenesis of Staphylococcus aureus infective endocarditis (IE) is postulated to involve invasion and damage of endothelial cells (ECs). However, the precise relationships between S. aureus–EC interactions in vitro and IE virulence and treatment outcomes in vivo are poorly defined. Ten methicillin‐resistant S. aureus (MRSA) clinical isolates previously tested for their virulence and vancomycin responsiveness in an experimental IE model were assessed in vitro for their haemolytic activity, protease production, and capacity to invade and damage ECs. There was a significant positive correlation between the in vitro EC damage caused by these MRSA strains and their virulence during experimental IE (in terms of bacterial densities in target tissues; P < 0.02). Importantly, higher EC damage was also significantly correlated with poor microbiological response to vancomycin in the IE model (P < 0.001). Interestingly, the extent of EC damage was unrelated to a strain's ability to invade ECs, haemolytic activity and protease production, or β‐toxin gene transcription. Inactivation of the agr locus in two MRSA strains caused ∼20% less damage as compared with the corresponding parental strains, indicating that a functional agr is required for maximal EC damage induction. Thus, MRSA‐induced EC damage in vitro is a unique virulence phenotype that is independent of many other prototypical MRSA virulence factors, and may be a key biomarker for predicting MRSA virulence potential and antibiotic outcomes during endovascular infections.
Off-label use of rituximab in a multipayer insurance system.

PURPOSE Off-label prescribing in oncology is common and unregulated. The aim of this study was to describe the off-label use of rituximab, a novel anti-CD20 antibody, among patients from a large proprietary insurance database to understand how frequently and appropriately off-label prescribing occurs for this medication. PATIENTS AND METHODS In this descriptive study, 11,232,642 patients were enrolled in the D2 Hawkeye commercial insurance database between 2001 and 2007, and 2,782 patients received rituximab. The main outcome measures were quantity and type of off-label usage, and expenditures for off-label usage. RESULTS Seven hundred five (25.3%) patients received rituximab for off-label indications, and of those, 332 (47.1%) received rituximab for uncertain or inadequate evidence-based diagnoses. Expenditures for off-label indications were 17.1% of expenditures for rituximab usage. CONCLUSION The frequent use of rituximab for off-label indications should lead to improved postapproval surveillance of biologics by the US Food and Drug Administration, so that use can be adequately studied. This will also facilitate improved regulatory mechanisms to ensure evidence-based use.
Propensity to Imitate in Autism Is Not Modulated by the Model's Gaze Direction: An Eye‐Tracking Study

Individuals with Autism Spectrum Disorder (ASD) show a diminished propensity to imitate others' actions, as well as a diminished sensitivity and responsivity to others' communicative cues, such as a direct gaze. However, it is not known whether failure to appreciate the communicative value of a direct gaze is associated with imitation abnormalities in this population. In this eye‐tracking study, we investigated how 25 preschoolers with ASD, compared with 25 developmental and chronological age‐matched children, imitate actions that are associated with a model's direct gaze versus averted gaze. We found that the model's direct gaze immediately prior to the demonstration increased the attention to the model and the propensity to imitate the demonstrated action in children without ASD. In contrast, preschoolers with ASD showed a similar propensity to look at the model's face and to imitate the demonstrated actions across the direct gaze and the averted gaze conditions. These data indicate that atypical imitation in ASD might be linked to abnormal processing of the model's communicative signals (such as a direct gaze) that modulate imitative behaviours in individuals without ASD. Autism Res 2014, 7: 392–399. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
Reliability assessment of power system containing wind farm based on steady-state power flow

Wind power is an intermittent and fluctuating energy source, which is quite different from conventional energy sources. Reliability evaluation on power system with wind power is an important issue. Monte Carlo method is a traditional approach, but it is not considering the steady-state operation of system. This paper presents a new method, which is based on steady-state power flow, for reliability evaluation of power system with wind power. The related reliability models including wind speed, wind turbine generator (WTG), conventional generator, and load are proposed. Finally, an example is analyzed, and four reliability indices are evaluated and compared on two conditions: with and without reactive power compensator. The results of the analysis confirm that the reactive power compensator can improve power system reliability.
Synergistic anti-HCV broadly neutralizing human monoclonal antibodies with independent mechanisms

Significance More than 71 million people are infected with HCV, and eradication of this pandemic will likely require a vaccine. Induction of broadly neutralizing monoclonal antibodies (bNAbs) is a goal of vaccine development, but no single bNAb neutralizes all strains of HCV. Here, we measured neutralizing activity of 35 combinations of neutralizing monoclonal antibodies (NAbs), showing that some NAbs form combinations with greater neutralizing breadth than any individual bNAb. One combination was also exceptionally potent because it blocks virus binding to three different HCV receptors. These data suggest that full-length envelope protein might have an advantage as a vaccine antigen relative to truncated protein or single-epitope scaffolds, since it might induce combinations of NAbs that are synergistic, with complementary neutralizing breadth. There is an urgent need for a vaccine to combat the hepatitis C virus (HCV) pandemic, and induction of broadly neutralizing monoclonal antibodies (bNAbs) against HCV is a major goal of vaccine development. Even within HCV genotype 1, no single bNAb effectively neutralizes all viral strains, so induction of multiple neutralizing monoclonal antibodies (NAbs) targeting distinct epitopes may be necessary for protective immunity. Therefore, identification of optimal NAb combinations and characterization of NAb interactions can guide vaccine development. We analyzed neutralization profiles of 12 human NAbs across diverse HCV strains, assigning the NAbs to two functionally distinct clusters. We then measured neutralizing breadth of 35 NAb combinations against genotype 1 isolates, with each combination including one NAb from each neutralization cluster. Many NAbs displayed complementary neutralizing breadth, forming combinations with greater neutralization across diverse strains than any individual bNAb. Remarkably, one of the most broadly neutralizing combinations of two NAbs, designated HEPC74/HEPC98, also displayed enhanced potency, with interactions matching the Bliss independence model, suggesting that these NAbs inhibit HCV infection through independent mechanisms. Subsequent experiments showed that HEPC74 primarily blocks HCV envelope protein binding to CD81, while HEPC98 primarily blocks binding to scavenger receptor B1 and heparan sulfate. Together, these data identify a critical vulnerability resulting from the reliance of HCV on multiple cell surface receptors, suggesting that vaccine induction of multiple NAbs with distinct neutralization profiles is likely to enhance the breadth and potency of the humoral immune response against HCV.
Bringing Masters' level skills to the clinical setting: What is the experience like for graduates of the Master of Science in manual therapy programme?

Introduction The nursing profession has been influential in conducting research to investigate the effect of continuing education programs on clinical practice. This research has indicated positive gains in competencies and behaviors, such as, becoming more research positive and dynamic as practitioners. There is, however, a dearth of studies investigating the clinical impact of Masters degrees in the physiotherapy profession. Purpose: The purpose of this study was to explore physiotherapists' experiences of change and/or development in their clinical practice after successfully completing a Masters in manual therapy degree. Study design and methodology: An exploratory qualitative, specifically phenomenological, approach was used. Semi-structured telephone interviews were conducted with seven Masters degree graduates, audio-taped, and transcribed. A foundational thematic analysis approach was used to analyze the data. Findings: Four main themes were identified: (1) precision thinking – an ability to integrate new skills and knowledge, so that care was patient-centered and based on available research evidence. (2) Clinical outputs – development of “ingenuity” in delivering efficient clinical practice. (3) Professional outputs – assuming an enhanced professional role (role model, education resource, and lifelong learner) in the workplace and acknowledging personal development. (4) Expectations – reviewing the relevance of pre-course expectations. Conclusions: This study provided evidence for the applicability to practice of the knowledge and skills gained in Masters education and suggested that the participants experienced substantial positive change across a broad spectrum of professional and personal issues.
SOURCES OF GENETIC AND PHENOTYPIC VARIANCE IN FERTILIZATION RATES AND LARVAL TRAITS IN A SEA URCHIN

Abstract In nonresource based mating systems females are thought to derive indirect genetic benefits by mating with high-quality males. Such benefits can be due either to the intrinsic genetic quality of sires or to beneficial interactions between maternal and paternal haplotypes. Animals with external fertilization and no parental care offer unrivaled opportunities to address these hypotheses. With these systems, cross-classified breeding designs and in vitro fertilization can be used to disentangle sources of genetic and environmental variance in offspring fitness. Here, we employ these approaches in the Australian sea urchin Heliocidaris erythrogramma and explore how sire-dam identities influence fertilization rates, embryo viability (survival to hatching), and metamorphosis, as well as the interrelationships between these potential fitness traits. We show that fertilization is influenced by a combination of strong maternal effects and intrinsic male effects. Our subsequent analysis of embryo viability, however, revealed a highly significant interaction between parental genotypes, indicating that partial incompatibilities can severely limit offspring survival at this life-history stage. Importantly, we detected no significant relationship between fertilization rates and embryo viability. This finding suggests that fertilization rates should not be inferred from hatching rates, which is commonly practiced in species in which it is not possible to estimate fertilization at conception. Finally, we detected significant additive genetic variance due to sires in rates of juvenile metamorphosis, and a positive correlation between fertilization rates and metamorphosis. This latter finding indicates that the performance of a male's ejaculate in noncompetitive IVF trials predicts heritable offspring traits, although the fitness implications of variance in rates of spontaneous juvenile metamorphosis have yet to be determined.
Enhanced recovery programmes can reduce length of stay after total knee replacement without sacrificing functional outcome at one year.

INTRODUCTION Enhanced recovery programmes (ERPs) are being widely adopted in total knee replacement (TKR) procedures but studies confirming that they have no adverse effects on functional outcomes are lacking. The aim of this study was to compare length of stay, postoperative functional outcome and range of motion at one year postoperatively between patients undergoing TKR with an ERP and those with traditional rehabilitation. METHODS A total of 165 consecutive patients undergoing primary unilateral TKR were included in the study. Overall, 84 patients undergoing TKR with an ERP were compared with a series of 81 patients undergoing primary unilateral TKR with traditional rehabilitation, immediately before the introduction of the ERP. RESULTS The median postoperative length of stay was 3 days in the ERP cohort and 4 in the traditionally rehabilitated cohort (p<0.001). There were no significant differences in the preintervention characteristics of the groups and there was no significant difference in operative time, transfusion or rates of manipulation under anaesthesia. There was no difference in magnitude of improvement in American Knee Society score (p=0.12) or range of motion (p=0.81) between the groups. CONCLUSIONS ERP can reduce length of stay after TKR while offering improvements in knee function equivalent to those experienced by patients undergoing TKR with traditional rehabilitation. Furthermore, ERP can be implemented successfully in the setting of a district general hospital.
Predictors of overweight and obesity among school going adolescents of Vadodara city in Western India

Abstract Background: Obesity among adolescents is escalating as a global epidemic which is associated with various lifestyle disorders in later life. Objective: To assess the factors influencing overweight and obesity among school going adolescents of Vadodara city in Western India. Methods: The study was carried out among 1050 school going adolescents from 15 schools selected by systematic random sampling after taking written informed consent from the participants. A predefined pretested semi-structured questionnaire was used to collect dietary information and physical activity. Anthropometric measurements such as height, weight, triceps skin fold thickness, waist and hip circumferences was measured using standard techniques. Adolescents were classified as overweight (>+1SD) and obese (>+2SD) with respect to their age and sex by using WHO reference charts. Factors found to be statistically significant in bivariate analysis were considered in the multiple logistic regression model. Results: Among 1050 school going adolescents, 7.8% were overweight and 2.7% were obese, making the combined prevalence of overweight and obesity as 10.5%. Among socio-demographic predictors: early and mid adolescence, male gender, English medium of instruction, positive family history of obesity were found to be the significantly associated with overweight/obesity among the study population. Whereas consumption of outside food, meal skipping habit, infrequent consumption of staple healthy food items were found to be significant diet related predictor variables for overweight/obesity. Among the physical activity predictors: sedentary activities, less outdoor games and sleep deprivation were also found to be significant predictors of overweight/obesity. Conclusion: Adolescents should be motivated to take adequate amount of healthy staple food like dal-rice at home and to engage in outdoor sports related activity to prevent overweight and obesity.
Managing the lipid profile of coronary heart disease patients

ABSTRACT Introduction: Lipid profile management is even more critical in patients treated for secondary prevention, since patients with established coronary heart disease are at higher risk of developing events. Current guidelines encourage lifestyle modification and patient engagement in disease prevention. However, the American College of Cardiology/American Heart Association guidelines seem to differ considerably from their predecessors, having an impact on clinical practice of lipid management. Area covered: This review article discusses and provides a summary of the current recommendations for lipid profile management in patients with coronary heart disease, with a view to present lifestyle modification and novel treatment strategies, and to indicate areas of dispute among recent guidelines. Expert commentary: Existing controversies between current guidelines concerning treatment goals and therapeutic decisions may have potential implications on the clinical management of patients. In the meantime, we eagerly wait for the results of randomized controlled trials evaluating promising, potent, safe and prolonged drugs that are in progress.
S-Nitrosylation of AtSABP3 Antagonizes the Expression of Plant Immunity*

Changes in cellular redox status are a well established response across phyla following pathogen challenge. In this context, the synthesis of nitric oxide (NO) is a conspicuous feature of plants responding to attempted microbial infection and this redox-based regulator underpins the development of plant immunity. However, the associated molecular mechanism(s) have not been defined. Here we show that NO accretion during the nitrosative burst promotes increasing S-nitrosylation of the Arabidopsis thaliana salicylic acid-binding protein 3 (AtSABP3) at cysteine (Cys) 280, suppressing both binding of the immune activator, salicylic acid (SA), and the carbonic anhydrase (CA) activity of this protein. The CA function of AtSABP3 is required for the expression of resistance in the host against attempted pathogen infection. Therefore, inhibition of AtSBAP3 CA function by S-nitrosylation could contribute to a negative feedback loop that modulates the plant defense response. Thus, AtSABP3 is one of the first targets for S-nitrosylation in plants for which the biological function of this redox-based post-translational modification has been uncovered. These data provide a molecular connection between the changes in NO levels triggered by attempted pathogen infection and the expression of disease resistance.