No abstract

Polycystic ovary syndrome (PCOS) affects over 10% of women. Insulin resistance, elevated free fatty acids (FFAs) and increased adiposity are key factors contributing to metabolic dysfunction in PCOS. We hypothesised that aberrant adipogenesis during adolescence, and downstream metabolic perturbations, contributes to the metabolic phenotype of adult PCOS. We used prenatally androgenized (PA) sheep as a clinically realistic model of PCOS. During adolescence, but not during fetal or early life of PA sheep, adipogenesis was decreased in subcutaneous adipose tissue (SAT) accompanied by decreased leptin, adiponectin, and increased FFAs. In adulthood, PA sheep developed adipocyte hypertrophy in SAT paralleled by increased expression of inflammatory markers, elevated FFAs and increased expression of genes linked to fat accumulation in visceral adipose tissue. This study provides better understanding into the pathophysiology of PCOS from puberty to adulthood and identifies opportunity for early clinical intervention to normalise adipogenesis and ameliorate the metabolic phenotype.

Background: There are concerns that the use of pre-exposure prophylaxis (PrEP) may result in an increased incidence of sexually transmitted infections (STIs). Evidence for this is mixed and has mostly been based on reviews focussed on gay and bisexual men and transgender women, while none have summarised evidence in cisgender women. Methods: We conducted a systematic review to explore whether daily, oral PrEP use is associated with changes in bacterial STI occurrence (diagnoses or self-reported) and/or risk among HIV seronegative cisgender women (ciswomen). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. Results: We included 11 full text articles in a narrative synthesis, with the studies published between 2012 and 2021. The studies were mostly based in Africa (n=7, 63.6%) and reported on 3168 ciswomen using PrEP aged 16–56 years. Studies had marked differences in variables, including measurements and definitions (e.g., STI type) and limited data available looking specifically at ciswomen, principally in studies with both male and female participants. The limited evidence suggests that PrEP use is not associated with increased STI rates in ciswomen generally; however, adolescent girls and young women in Sub Saharan Africa have a higher prevalence of bacterial STIs prior to PrEP initiation, compared to adult ciswomen and female sex workers. Conclusions: We suggest future PrEP research make efforts to include ciswomen as study participants and report stratified results by gender identity to provide adequate data to inform guidelines for PrEP implementation. PROSPERO registration: CRD42019130438

Background The emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated. Aim Our aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type. Methods Laboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death. Results Of 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality. Conclusion We found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.