Ryandobson9616
© 2020, Kakebeen et al.The ability of the immune system to avoid autoimmune disease relies on tolerization of thymocytes to self-antigens whose expression and presentation by thymic medullary epithelial cells (mTECs) is controlled predominantly by Aire at the transcriptional level and possibly regulated at other unrecognized levels. Aire-sensitive gene expression is influenced by several molecular factors, some of which belong to the 3'end processing complex, suggesting they might impact transcript stability and levels through an effect on 3'UTR shortening. We discovered that Aire-sensitive genes display a pronounced preference for short-3'UTR transcript isoforms in mTECs, a feature preceding Aire's expression and correlated with the preferential selection of proximal polyA sites by the 3'end processing complex. Through an RNAi screen and generation of a lentigenic mouse, we found that one factor, Clp1, promotes 3'UTR shortening associated with higher transcript stability and expression of Aire-sensitive genes, revealing a post-transcriptional level of control of Aire-activated expression in mTECs. © 2020, Guyon et al.BACKGROUND Langerhans cells (LCs) polarize the immune milieu towards a T helper type (Th) 1 or Th2 immune response. We investigated the effects of selected tetracyclines on Th cells development mediated by LCs, and their implications for the treatment of atopic dermatitis (AD). METHODS Mice were primed with ovalbumin (OVA) peptide-pulsed LCs, which had been treated with each antibiotic, via the hind footpad. After 5 days, the Th1/Th2 cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The therapeutic effects of a selected antibiotic on AD-like skin lesions of NC/Nga mice were assessed in terms of the skin severity score, histological changes in the lesioned skin, the serum level of total IgE, and expression of Th1/Th2 cytokines in lymph nodes and skin lesions. RESULTS Antibiotic-treated, OVA peptide-pulsed LCs inhibited development of Th2 cells but not Th1 cells. This was accompanied by suppression of T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs. Doxycycline had the greatest activity against Staphylococcus aureus strains isolated from skin lesions of patients with AD, and a strong inhibitory effect on Th2 cell development. Doxycycline suppressed the increase in the skin severity score during the acute phase in NC/Nga mice similar to betamethasone. This suppressive effect was associated with a decrease in the serum IgE level and production of Th2 cytokines in auricular lymph node cells and skin lesions. CONCLUSION Topical application of doxycycline to AD lesions would act on both superficial S. aureus colonization and epidermal LCs, thus possibly inhibiting the development of Th2 cells in vivo, with benefits for control of acute inflammation in AD.In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally.Background Randomised controlled trials (RCTs) are a gold standard for evaluations in public health, economics and social sciences, including prevention of violence against women (VAW). They substantially reduce bias, but do not eliminate measurement error. Control arms often show change, but this is rarely systematically examined.Objective We present a secondary analysis of data from the control arms of evaluations of VAW prevention programming to understand measurement variance over time, factors that may systematically impact this and make recommendations for stronger trial design and interpretation.Methods We examine data from six RCTs and one quasi-experimental study, all of which used comparable measures. We look at change over time among control participants in prevalence of physical intimate partner violence (IPV), sexual IPV, and severe physical/sexual IPV, by participants' gender and study design (cohort vs. repeat cross-sectional).Results On average, repeated assessments of past year IPV varied by 3.21 (95%Cis 1.59,4.83) percentage points for the studies with no active control arms. The prevalence at endline, as a proportion of that at baseline, on average differed by 17.7%. In 10/35 assessments from 4/7 studies, the difference was more than 30%. We did not find evidence of the Hawthorne effect or repeat interview bias as explanations. Our findings largely supported non-differential misclassification (measurement error) as the most likely error and it was a greater problem for men.Conclusions Control arms are very valuable, but in VAW research their measures fluctuate. This must be considered in sample size calculations. We need more rigorous criteria for determining trial effect. Our findings suggest this may be an absolute change in prevalence of 7% and proportionate change of 0.4 or more (especially for studies in populations with lower IPV prevalence ( less then 20%)). More elaborate pre-defined outcomes are necessary for determining impact (or possible harms) of VAW prevention interventions.Background Social factors modulating stroke outcomes are found to be culturally and gender inclined. We examined social support and social constraints in Hausa women stroke survivors.Aim To determine social support and social constraints in Hausa women after stroke.Materials and methods Seventy-four (74) Hausa women stroke survivors were conveniently recruited from three tertiary health centers to participate in this cross-sectional study. Sociodemographic and stroke-related attributes of the participants were obtained. Perceived social support and social constraints were assessed using multidimentional scale of perceived social support (MSPSS) and the social problem questionnaire (SPQ), respectively. https://www.selleckchem.com/products/bpv-hopic.html The relationship and association between different variables were assessed using Pearson's correlation and chi-square test, respectively.Results Majority of the participants (60.8%) reported adequate level of social support. Similarly, most participants reported fairly low level of social constraints in total family stress (91.