Neutrophils from Both Susceptible and Resistant Mice Efficiently Kill Opsonized \u3cem\u3eListeria monocytogenes\u3c/em\u3e

Inbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacterium Listeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (polymorphonuclear leukocytes [PMN]) were particularly important for clearance in the liver, but the ability of PMN from susceptible and resistant mice to directly kill L. monocytogenes has not been examined. In this study, we showed that PMN infiltrated the livers of BALB/c/By/J (BALB/c) and C57BL/6 (B6) mice in similar numbers and that both cell types readily migrated toward leukotriene B4 in an in vitro chemotaxis assay. However, CFU burdens in the liver were significantly higher in BALB/c mice than in other strains, suggesting that PMN in the BALB/c liver might not be able to clear L. monocytogenes as efficiently as B6 PMN. Unprimed PMN harvested from either BALB/c or B6 bone marrow killed L. monocytogenes directly ex vivo, and pretreatment with autologous serum significantly enhanced killing efficiency for both. L. monocytogenes were internalized within 10 min and rapidly triggered intracellular production of reactive oxygen species in a dose-dependent manner. However, PMN from gp91phox-deficient mice also readily killed L. monocytogenes, which suggested that nonoxidative killing mechanisms may be sufficient for bacterial clearance. Together, these results indicate that there is not an intrinsic defect in the ability of PMN from susceptible BALB/c mice to kill L. monocytogenes and further suggest that if PMN function is impaired in BALB/c mice, it is likely due to locally produced modulating factors present in the liver during infection

Prevalence of treated autism spectrum disorders in Aruba

To study autism outside of a narrow range of settings previously studied, and in a particularly distinctive setting in the Caribbean. The aim of the Aruba Autism Project was to determine the prevalence of autism spectrum disorders (ASDs) in birth years 1990–1999 in Aruba. A record review study was conducted; cases were ascertained from children treated at the Child & Adolescent Psychiatry Clinic of Aruba, the first and only child psychiatry service on the island. In these 10 birth years we found a prevalence for autistic disorder (AD) of 1.9 per 1,000 (95% CI 1.2–2.8) and for autism spectrum disorders of 5.3 per 1,000 (95% CI 4.1–6.7). Comparison analysis with a cumulative incidence report from the UK, showed a similar cumulative incidence to age five in Aruba. Prevalence of ASDs in birth years 1990–1999 and cumulative incidence to age five in Aruba are similar to recent reports from the United Kingdom and the United States

Effectiveness of a computer assisted learning (CAL) package to raise awareness of autism

<p>Abstract</p> <p>Background</p> <p>Promoting awareness of autism in populations who work with children may result in an earlier diagnosis of the condition. In this study, a computer assisted learning (CAL) package, containing educationally appropriate knowledge about autism was developed; and the effectiveness of this CAL package was evaluated.</p> <p>Methods</p> <p>The CAL package was developed using computer software, "Xerte" and "Flash Macromedia". The effectiveness of the CAL package was evaluated in 32 childcare students in the UK, who were randomised to watch the CAL package or to read the information leaflet containing the same information (n = 16 in each group). Retention performance, level of enjoyment, and level of confidence to identify a child with autism, after the interventions, were evaluated. The data obtained from two studied groups was analysed using unpaired Student's t-test, 95% confidence interval, and effect size.</p> <p>Results</p> <p>Students who watched the CAL package had superior retention performance percentage scores (p = 0.02, 95% CI = 0.83–12.19, effect size = 0.8) and level of enjoyment (p = 0.04, 95% CI = 0.03–2.75, effect size = 0.7) compared with students who read the information leaflet. However, there was no significant difference in level of confidence to identify a child with autism (p = 0.39, 95% CI = -1.80–0.72, effect size = -0.3).</p> <p>Conclusion</p> <p>The CAL package developed was an effective method of educating people who work with children about autism.</p

Night Myopia Studied with an Adaptive Optics Visual Analyzer

PURPOSE: Eyes with distant objects in focus in daylight are thought to become myopic in dim light. This phenomenon, often called "night myopia" has been studied extensively for several decades. However, despite its general acceptance, its magnitude and causes are still controversial. A series of experiments were performed to understand night myopia in greater detail. METHODS: We used an adaptive optics instrument operating in invisible infrared light to elucidate the actual magnitude of night myopia and its main causes. The experimental setup allowed the manipulation of the eye's aberrations (and particularly spherical aberration) as well as the use of monochromatic and polychromatic stimuli. Eight subjects with normal vision monocularly determined their best focus position subjectively for a Maltese cross stimulus at different levels of luminance, from the baseline condition of 20 cd/m(2) to the lowest luminance of 22 × 10(-6) cd/m(2). While subjects performed the focusing tasks, their eye's defocus and aberrations were continuously measured with the 1050-nm Hartmann-Shack sensor incorporated in the adaptive optics instrument. The experiment was repeated for a variety of controlled conditions incorporating specific aberrations of the eye and chromatic content of the stimuli. RESULTS: We found large inter-subject variability and an average of -0.8 D myopic shift for low light conditions. The main cause responsible for night myopia was the accommodation shift occurring at low light levels. Other factors, traditionally suggested to explain night myopia, such as chromatic and spherical aberrations, have a much smaller effect in this mechanism. CONCLUSIONS: An adaptive optics visual analyzer was applied to study the phenomenon of night myopia. We found that the defocus shift occurring in dim light is mainly due to accommodation errors

Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor Cell Line Panels.

Loss-of-function screening using RNA interference or CRISPR approaches can be used to identify genes that specific tumor cell lines depend upon for survival. By integrating the results from screens in multiple cell lines with molecular profiling data, it is possible to associate the dependence upon specific genes with particular molecular features (e.g., the mutation of a cancer driver gene, or transcriptional or proteomic signature). Here, using a panel of kinome-wide siRNA screens in osteosarcoma cell lines as an example, we describe a computational protocol for analyzing loss-of-function screens to identify genetic dependencies associated with particular molecular features. We describe the steps required to process the siRNA screen data, integrate the results with genotypic information to identify genetic dependencies, and finally the integration of protein-protein interaction data to interpret these dependencies

Reading comprehension in autism spectrum disorders: The role of oral language and social functioning

Reading comprehension is an area of difficulty for many individuals with autism spectrum disorders (ASD). According to the Simple View of Reading, word recognition and oral language are both important determinants of reading comprehension ability. We provide a novel test of this model in 100 adolescents with ASD of varying intellectual ability. Further, we explore whether reading comprehension is additionally influenced by individual differences in social behaviour and social cognition in ASD. Adolescents with ASD aged 14-16 years completed assessments indexing word recognition, oral language, reading comprehension, social behaviour and social cognition. Regression analyses show that both word recognition and oral language explain unique variance in reading comprehension. Further, measures of social behaviour and social cognition predict reading comprehension after controlling for the variance explained by word recognition and oral language. This indicates that word recognition, oral language and social impairments may constrain reading comprehension in ASD

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition,Economics (DAnCE) fall prevention randomised controlled trial

Background:&nbsp; Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the &lsquo;holistic&rsquo; approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. Methods/design: A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. Discussion: This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise

Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes: A Meta-Analysis of Published Studies and Recommendations

Despite discrepant results on clinical utility, several trials are already prospectively randomizing non-small cell lung cancer (NSCLC) patients by ERCC1 status. We aimed to characterize the prognostic and predictive effect of ERCC1 by systematic review and meta-analysis.Eligible studies assessed survival and/or chemotherapy response in NSCLC or SCLC by ERCC1 status. Effect measures of interest were hazard ratio (HR) for survival or relative risk (RR) for chemotherapy response. Random-effects meta-analyses were used to account for between-study heterogeneity, with unadjusted/adjusted effect estimates considered separately.23 eligible studies provided survival results in 2,726 patients. Substantial heterogeneity was observed in all meta-analyses (I(2) always >30%), partly due to variability in thresholds defining 'low' and 'high' ERCC1. Meta-analysis of unadjusted estimates showed high ERCC1 was associated with significantly worse overall survival in platinum-treated NSCLC (average unadjusted HR = 1.61, 95%CI:1.23-2.1, p = 0.014), but not in NSCLC untreated with chemotherapy (average unadjusted HR = 0.82, 95%CI:0.51-1.31). Meta-analysis of adjusted estimates was limited by variable choice of adjustment factors and potential publication bias (Egger's p<0.0001). There was evidence that high ERCC1 was associated with reduced response to platinum (average RR = 0.80; 95%CI:0.64-0.99). SCLC data were inadequate to draw firm conclusions.Current evidence suggests high ERCC1 may adversely influence survival and response in platinum-treated NSCLC patients, but not in non-platinum treated, although definitive evidence of a predictive influence is lacking. International consensus is urgently required to provide consistent, validated ERCC1 assessment methodology. ERCC1 assessment for treatment selection should currently be restricted to, and evaluated within, clinical trials

A probabilistic framework to predict protein function from interaction data integrated with semantic knowledge

<p>Abstract</p> <p>Background</p> <p>The functional characterization of newly discovered proteins has been a challenge in the post-genomic era. Protein-protein interactions provide insights into the functional analysis because the function of unknown proteins can be postulated on the basis of their interaction evidence with known proteins. The protein-protein interaction data sets have been enriched by high-throughput experimental methods. However, the functional analysis using the interaction data has a limitation in accuracy because of the presence of the false positive data experimentally generated and the interactions that are a lack of functional linkage.</p> <p>Results</p> <p>Protein-protein interaction data can be integrated with the functional knowledge existing in the Gene Ontology (GO) database. We apply similarity measures to assess the functional similarity between interacting proteins. We present a probabilistic framework for predicting functions of unknown proteins based on the functional similarity. We use the leave-one-out cross validation to compare the performance. The experimental results demonstrate that our algorithm performs better than other competing methods in terms of prediction accuracy. In particular, it handles the high false positive rates of current interaction data well.</p> <p>Conclusion</p> <p>The experimentally determined protein-protein interactions are erroneous to uncover the functional associations among proteins. The performance of function prediction for uncharacterized proteins can be enhanced by the integration of multiple data sources available.</p