Metagenomic analysis of viruses in toilet waste from long distance flights—A new procedure for global infectious disease surveillance

<div><p>Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.</p></div

Role of the HSP90-Associated Cochaperone p23 in Enhancing Activity of the Androgen Receptor and Significance for Prostate Cancer

Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly understood but it may be that changes in levels or activity of AR coregulators affect trafficking and activation of the receptor. A key stage in AR signaling occurs in the cytoplasm, where unliganded receptor is associated with the heat shock protein (HSP)90 foldosome complex. p23, a key component of this complex, is best characterized as a cochaperone for HSP90 but also has HSP90-independent activity and has been re-ported as having differential effects on the activity of different steroid receptors. Here we report that p23 increases activity of the AR, and this appears to involve steps both in the cytoplasm (increasing ligand-binding capacity, possibly via direct interaction with AR) and the nucleus (en-hancing AR occupancy at target promoters). We show, for the first time, that AR and p23 can interact, perhaps directly, when HSP90 is not present in the same complex. The effects of p23 on AR activity are at least partly HSP90 independent because a mutant form of p23, unable to bind HSP90, nevertheless increases AR activity. In human prostate tumors, nuclear p23 was higher in malignant prostate cells compared with benign/normal cells, supporting the utility of p23 as a therapeutic target in prostate cancer. © 2012 by The Endocrine Society

Profiles of GPs with high and low self-reported physician empathy—personal, professional, and antibiotic prescribing characteristics

BackgroundGeneral Practitioners' (GPs) professional empathy has been hypothesized to have substantial impact on their healthcare delivery and medication prescribing patterns. This study compares profiles of personal, professional, and antibiotic prescribing characteristics of GPs with high and low empathy.MethodsWe apply an extreme group approach to a unique combined set of survey and drug register data. The survey included questions about demographic, professional, and antibiotic prescribing characteristics, as well as the Jefferson Scale of Empathy for Health Professionals (JSE-HP) to assess self-reported physician empathy. It was sent to a stratified sample of 1,196 GPs comprising 30% of the Danish GP population of whom 464 (38.8%) GPs responded. GPs in the top and bottom decile of empathy levels were identified. All intra- and inter-profile descriptive statistics and differences were bootstrapped to estimate the variability and related confidence intervals.&nbsp; RESULTS: 61% of GPs in the top decile of the empathy score were female. GPs in this decile reported the following person-centered factors as more important for their job satisfaction than the bottom decile: The Patient-physician relationship, interaction with colleagues, and intellectual stimulation. High-empathy scoring GPs prescribed significantly less penicillin than the low-empathy GPs. This was true for most penicillin subcategories. There were no significant differences in age, practice setting (urban vs. rural), practice type (partnership vs. single-handed), overall job satisfaction, or GP's value of prestige and economic profit for their job satisfaction. The intra profile variation index and confidence intervals show less prescribing uncertainty among GPs with high empathy.ConclusionsThis study reveals that high empathy GPs may have different personal, professional, and antibiotic prescribing characteristics than low empathy GPs and have less variable empathy levels as a group. Furthermore, person-centered high empathy GPs on average seem to prescribe less penicillins than low empathy GPs