Background Norovirus infection is the leading cause of acute non-bacterial gastroenteritis. Histoblood group antigens (HBGA) are host susceptibility determinants for Norwalk virus (NV) infection. We hypothesized that antibodies that block NV-HBGA binding are associated with protection from clinical illness following NV exposure. Methods We developed an HBGA blocking assay to examine the ability of human serum to block the interaction of NV virus-like particles with H type 1 and H type 3 glycans. Sera from persons experimentally challenged with NV were evaluated. Results There was a high correlation between the H type 1 and H type 3 synthetic glycan assays(r=0.977, p<0.0001); the H type 1 assay had higher quantitative sensitivity (p<0.0001). Among 18 infected secretor-positive individuals, blocking titers peaked by day 28 post-challenge and were higher for individuals who did not develop gastroenteritis than for those who did at days 0,14,28, and 180 (p<0.05 for each). Additionally, 6/6 without gastroenteritis had measurable blocking titers (>25)compared to 2/12 with gastroenteritis (p=0.0015). Conclusions Blocking antibodies correlate with protection against clinical NV gastroenteritis. This knowledge will help guide the evaluation of new vaccine strategies, and elucidation of the nature of immunity to the virus.

Given the considerable lack of evidence supporting its efficacy, we recommend against routine performance of DRE to screen for prostate cancer in the primary care setting.

The transport properties (adsorption and aggregation behavior) of virus-like particles (VLPs) of two strains of norovirus (“Norwalk” GI.1 and “Houston” GII.4) were studied in a variety of solution chemistries. GI.1 and GII.4 VLPs were found to be stable against aggregation at pH 4.0–8.0. At pH 9.0, GI.1 VLPs rapidly disintegrated. The attachment efficiencies (α) of GI.1 and GII.4 VLPs to silica increased with increasing ionic strength in NaCl solutions at pH 8.0. The attachment efficiency of GI.1 VLPs decreased as pH was increased above the isoelectric point (pH 5.0), whereas at and below the isoelectric point, the attachment efficiency was erratic. Ca2+ and Mg2+ dramatically increased the attachment efficiencies of GI.1 and GII.4 VLPs, which may be due to specific interactions with the VLP capsids. Bicarbonate decreased attachment efficiencies for both GI.1 and GII.4 VLPs, whereas phosphate decreased the attachment efficiency of GI.1, while increasing GII.4 attachment efficiency. The observed differences in GI.1 and GII.4 VLP attachment efficiencies in response to solution chemistry may be attributed to differential responses of the unique arrangement of exposed amino acid residues on the capsid surface of each VLP strain.

Background: Burnout among postgraduate medical trainees (PMTs) is increasingly being recognized as a crisis in the medical profession. We aimed to establish the prevalence of burnout among PMTs, identify risk and protective factors, and assess whether burnout varied by country of training, year of study and specialty of practice. Methods: We systematically searched MEDLINE, Embase, PsycINFO, the Cochrane Database of Systematic Reviews, Web of Science and Education Resources Information Center from their inception to Aug. 21, 2018, for studies of burnout among PMTs. The primary objective was to identify the global prevalence of burnout among PMTs. Our secondary objective was to evaluate the association between burnout and country of training, year of study, specialty of training and other sociodemographic factors commonly thought to be related to burnout. We employed random-effects meta-analysis and meta-regression techniques to estimate a pooled prevalence and conduct secondary analyses. Results: In total, 8505 published studies were screened, 196 met eligibility and 114 were included in the meta-analysis. The pooled prevalence of burnout was 47.3% (95% confidence interval 43.1% to 51.5%), based on studies published over 20 years involving 31 210 PMTs from 47 countries. The prevalence of burnout remained unchanged over the past 2 decades. Burnout varied by region, with PMTs of European countries experiencing the lowest level. Burnout rates among medical and surgical PMTs were similar. Interpretation: Current wellness efforts and policies have not changed the prevalence of burnout worldwide. Future research should focus on understanding systemic factors and leveraging these findings to design interventions to combat burnout. Study registration: PROSPERO no. CRD42018108774