IL-36R signaling integrates innate and adaptive immune-mediated protection against enteropathogenic bacteria.

Enteropathogenic bacterial infections are a global health issue associated with high mortality, particularly in developing countries. Efficient host protection against enteropathogenic bacterial infection is characterized by coordinated responses between immune and nonimmune cells. In response to infection in mice, innate immune cells are activated to produce interleukin (IL)-23 and IL-22, which promote antimicrobial peptide (AMP) production and bacterial clearance. IL-36 cytokines are proinflammatory IL-1 superfamily members, yet their role in enteropathogenic bacterial infection remains poorly defined. Using the enteric mouse pathogen, C.rodentium, we demonstrate that signaling via IL-36 receptor (IL-36R) orchestrates a crucial innate-adaptive immune link to control bacterial infection. IL-36R-deficient mice (Il1rl2-/- ) exhibited significant impairment in expression of IL-22 and AMPs, increased intestinal damage, and failed to contain C. rodentium compared to controls. These defects were associated with failure to induce IL-23 and IL-6, two key IL-22 inducers in the early and late phases of infection, respectively. Treatment of Il1rl2-/- mice with IL-23 during the early phase of C. rodentium infection rescued IL-22 production from group 3 innate lymphoid cells (ILCs), whereas IL-6 administration during the late phase rescued IL-22-mediated production from CD4+ T cell, and both treatments protected Il1rl2-/- mice from uncontained infection. Furthermore, IL-36R-mediated IL-22 production by CD4+ T cells was dependent upon NFκB-p65 and IL-6 expression in dendritic cells (DCs), as well as aryl hydrocarbon receptor (AhR) expression by CD4+ T cells. Collectively, these data demonstrate that the IL-36 signaling pathway integrates innate and adaptive immunity leading to host defense against enteropathogenic bacterial infection.

A 7-year longitudinal study of sexual minority young men's parental relationships and mental health.

While existing research documents the impact of parental rejection on sexual minorities, the present study extends this research to include a subtler, yet potentially more pervasive, challenge facing sexual minorities and their parents, with lasting implications for mental health. Parental unfinished business refers to persistent, unresolved negative thoughts and feelings toward one's parents and is investigated here as a result of parental rejection of their sexual minority sons' sexual orientation. To capture developmental trajectories of parental unfinished business and its prospective predictors (i.e., rejection) and outcomes (i.e., depressive symptoms, social anxiety, alcohol abuse), young sexual minority men (n = 113; baseline Mage = 20.78) reported their experience of these constructs annually for 7 years. Results revealed significantly decreasing trajectories of unfinished business with mothers, but not fathers, over 7 years. Parental rejection of their son's sexual orientation prospectively predicted greater next-year unfinished business. Unfinished business with fathers prospectively predicted next-year depressive symptoms. Prospective effects did not extend to next-year social anxiety or alcohol abuse for unfinished business with either parent. This study positions unfinished business as a novel, distinct, and important component of young sexual minority men's identity development and depression and examines these constructs over seven formative years. Findings can inform theoretical accounts of sexual minority development and clinical case formulation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Determinants of first trimester attendance at antenatal care clinics in the Amazon region of Peru: A case-control study.

OBJECTIVE: To identify determinants which influence the timing of the first antenatal care (ANC) visit in pregnant women. DESIGN: Retrospective matched nested case-control study. SETTING: Two health centres, Belén and 6 de Octubre, in the Peruvian Amazon. POPULATION: All pregnant women who had attended ANC during the years 2010, 2011, and 2012. METHODS: All cases (819 women initiating ANC in their first trimester) were selected from ANC registries from 2010 to 2012. A random sample of controls (819 women initiating ANC in their second or third trimester) was matched 1:1 to cases on health centre and date of first ANC visit. Data were obtained from ANC registries. Conditional logistic regression analyses were performed. MAIN OUTCOME MEASURE: Case-control status of each woman determined by the gestational age at first ANC visit. RESULTS: Cases had higher odds of: 1) being married or cohabiting (aOR = 1.69; 95% CI: 1.19, 2.41); 2) completing secondary school or attending post-secondary school (aOR = 1.45; 95% CI: 1.02, 2.06); 3) living in an urban environment (aOR = 1.79; 95% CI: 1.04, 3.10) and 4) having had a previous miscarriage (aOR = 1.56; 95% CI: 1.13, 2.15), compared to controls. No statistically significant difference in odds was found for parity (aOR = 1.08; 95% CI: 0.85, 1.36). CONCLUSIONS: This study provides empirical evidence of determinants of first ANC attendance. These findings are crucial to the planning and timing of local interventions, like deworming, aimed at pregnant women so that they can access and benefit fully from all government-provided ANC services.