77 to 8.14; functional limitations HRs 6.65 to 10.42; depression HRs 3.30 to 5.56). In the Netherlands (functional limitations) and England (functional limitations and SRH), effects were stronger in the lower educated. CONCLUSIONS The prevalence of health problems, that is, poor SRH, functional limitations and depression, was higher in the lower educated workers. All three health indicators increase the risk of early work exit. In some countries, health effects on early exit were stronger in the lower educated. Thus, lower educated older workers are an important target group for health policy and intervention. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND The History Electrocardiogram Age Risk factor Troponin (HEART) Pathway and Emergency Department Assessment of Chest pain Score (EDACS) are validated accelerated diagnostic pathways designed to risk stratify patients presenting to the emergency department with chest pain. Data from large multisite prospective studies comparing these accelerated diagnostic pathways are limited. METHODS The HEART Pathway Implementation is a prospective three-site cohort study, which accrued adults with symptoms concerning for acute coronary syndrome. Physicians completed electronic health record HEART Pathway and EDACS risk assessments on participants. Major adverse cardiac events (death, myocardial infarction and coronary revascularisation) at 30 days were determined using electronic health record, insurance claims and death index data. Test characteristics for detection of major adverse cardiac events were calculated for both accelerated diagnostic pathways and McNemar's tests were used for comparisons. https://www.selleckchem.com/products/tj-m2010-5.html RESULTS 5799r risk tolerance when deciding whether to adopt the HEART Pathway or EDACS accelerated diagnostic pathway. TRIAL REGISTRATION NUMBER NCT02056964. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The systemic right ventricle (SRV), defined as the morphological right ventricle supporting the systemic circulation, is relatively common in congenital heart disease (CHD). Our review aimed at examining the current evidence, knowledge gaps and technical considerations regarding implantable cardiac electronic device therapy in patients with SRV. The risk of sinus node dysfunction (SND) after atrial switch repair and/or complete heart block in congenitally corrected transposition of great arteries requiring permanent pacing increases with age. Similar to acquired heart disease, indication for pacing includes symptomatic bradycardia, SND and high degree atrioventricular nodal block. Right ventricular dysfunction and heart failure also represent important complications in SRV patients. Cardiac resynchronisation therapy (CRT) has been proposed to improve systolic function in SRV patients, although indications for CRT are not well defined and its potential benefit remains uncertain. Amongst adult CHD, patients with SRV are at the highest risk for sudden cardiac death (SCD). Nevertheless, risk stratification for SCD is scarce in this cohort and implantable cardioverter-defibrillator indication is currently limited to secondary prevention. Vascular access and the incidence of device-related complications, such as infections, inappropriate shocks and device system failure, represent additional challenges to implantable cardiac electronic device therapy in patients with SRV. A multidisciplinary approach with tertiary expertise and future collaborative research are all paramount to further the care for this challenging nonetheless ever increasing cohort of patients. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Concurrent sexually transmitted infections (STI) can increase the probability of HIV-1 transmission primarily by increasing the viral load present in semen. In this study, we explored the relationship of HIV-1 in blood and seminal plasma in the presence and absence of urethritis and after treatment of the concurrent STI. Primer ID deep sequencing of the V1/V3 region of the HIV-1 env gene was done for paired blood and semen samples from ART-naïve men living in Malawi with (n = 19) and without (n = 5) STI-associated urethritis; for a subset of samples full length env genes were generated for sequence analysis and to test entry phenotype. Cytokine concentrations in the blood and semen were also measured, and a reduction in the levels of pro-inflammatory cytokines was observed following STI treatment. We observed no difference in the prevalence of diverse compartmentalized semen-derived lineages in men with or without STI-associated urethritis, and these viral populations were largely stable during STI treatment. Clonal amplification of one or a few viral sequences accounted for nearly 50% of the viral population indicating a recent bottleneck followed by limited viral replication. We conclude that the male genital tract is a site where virus can be brought in from the blood, where localized sustained replication can occur, and where specific genotypes can be amplified perhaps initially by cellular proliferation but further by limited viral replication.IMPORTANCE HIV-1 is a sexually transmitted infection that co-exists with other STIs. Here we examine the impact of a concurrent STI resulting in urethritis on the HIV-1 population within the male genital tract. We found that viral populations remain largely stable even with treatment of the STI. These results show that viral populations within the male genital tract are defined by factors beyond transient inflammation associated with a concurrent STI. Copyright © 2020 American Society for Microbiology.Eukaryotic single-stranded (ss) DNA viruses are classified into ten families (Table 1) but many remain 38 unclassified (1, 2).…. Copyright © 2020 American Society for Microbiology.Positive-strand (+)RNA viruses assemble numerous membrane-bound viral replicase complexes (VRCs) with the help of viral replication proteins and co-opted host proteins within large viral replication compartments in the cytosol of the infected cells. In this paper, we find that deletion or depletion of Sac1 PI4P phosphatase reduced tomato bushy stunt virus (TBSV) replication in yeast and plants. We demonstrate a critical role for Sac1 in TBSV replicase assembly in a cell-free replicase reconstitution assay. The effect of Sac1 seems to be direct based on its interaction with the TBSV p33 replication protein, co-purification with the tombusvirus replicase, and its presence in the virus-induced membrane contact sites and within the TBSV replication compartment. The pro-viral functions of Sac1 include manipulation of lipid composition, sterol enrichment within the VRCs and recruitment of additional host factors into VRCs. Depletion of Sac1 inhibited the recruitment of the Rab5 GTPase-positive endosomes and enrichment of phosphatidylethanolamine in the viral replication compartment.