MicroRNAs in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to or witnessing of a (potentially) threatening event. A critical issue is to pinpoint the (neuro)biological mechanisms underlying the susceptibility to stress-related disorder such as PTSD, which develops in the minority of ~15% of individuals exposed to trauma. Over the last few years, a first wave of epigenetic studies has been performed in an attempt to identify the molecular underpinnings of the long-lasting behavioral and mental effects of trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) in moderating or mediating the impact of severe stress and trauma are increasingly gaining attention. To date, most studies focusing on the roles of miRNAs in PTSD have, however, been completed in animals, using cross-sectional study designs and focusing almost exclusively on subjects with susceptible phenotypes. Therefore, there is a strong need for new research comprising translational and cross-species approaches that use longitudinal designs for studying trajectories of change contrasting susceptible and resilient subjects. The present review offers a comprehensive overview of available studies of miRNAs in PTSD and discusses the current challenges, pitfalls, and future perspectives of this field

MicroRNAs in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to or witnessing of a (potentially) threatening event. A critical issue is to pinpoint the (neuro)biological mechanisms underlying the susceptibility to stress-related disorder such as PTSD, which develops in the minority of ~15% of individuals exposed to trauma. Over the last few years, a first wave of epigenetic studies has been performed in an attempt to identify the molecular underpinnings of the long-lasting behavioral and mental effects of trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) in moderating or mediating the impact of severe stress and trauma are increasingly gaining attention. To date, most studies focusing on the roles of miRNAs in PTSD have, however, been completed in animals, using cross-sectional study designs and focusing almost exclusively on subjects with susceptible phenotypes. Therefore, there is a strong need for new research comprising translational and cross-species approaches that use longitudinal designs for studying trajectories of change contrasting susceptible and resilient subjects. The present review offers a comprehensive overview of available studies of miRNAs in PTSD and discusses the current challenges, pitfalls, and future perspectives of this field

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated