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BackgroundA recent resurgence of bacterial sexually transmitted infections (STIs) is placing a major burden on high-risk populations, physicians, and the healthcare system. Treatment in the form of antibiotic pre-exposure prophylaxis (STI PrEP) is a potential solution. However, little is known about the acceptability and feasibility of this approach in high-risk populations.MethodsA comprehensive search strategy was developed and executed in October 2024 across six databases adhering to PRISMA guidelines.ResultsEight studies met the inclusion criteria. These studies were all conducted in high-income countries, used various methods, and all focussed on sexual minority men. Findings consistently identified moderate to high levels of acceptability among GBMSM (54.3% - 67.5%). Factors such as engagement in perceived 'high risk' sexual encounters, and past diagnosis of STIs strengthened acceptability, while others (e.g., antimicrobial resistance concerns and stigma) act as barriers. Only one study included the perspectives of healthcare workers, indicating a moderate willingness to prescribe, which would increase under governing-body endorsement.DiscussionOverall, while there is some promise of STI PrEP acceptability among GBMSM, vast gaps in knowledge remain. Knowledge transfer and feasibility and, hence, the sustainability and capacity needed for the success of STI PrEP is yet to be examined and understood. However, for STI PrEP to be successfully adopted, it is essential not only to assess its acceptability and feasibility but also to focus on knowledge transfer. Knowledge transfer is a dynamic and iterative process, involving the synthesis, dissemination, exchange, and application of knowledge in an ethically sound manner. This process supports the improvement of health outcomes, strengthens healthcare systems, and ensures that healthcare interventions, such as STI PrEP, are effectively understood and implemented by both healthcare providers and at-risk populations. Similarly, the perspectives of populations beyond GBMSM have been omitted, and there is little understanding of the impact of their differing socio-cultural contexts around sex-related behaviour and Western pharmaceutical healthcare interventions on their acceptance and uptake.ConclusionFurther research into acceptability, feasibility and knowledge transfer among diverse high-risk groups, healthcare professionals, and policymakers is necessary to create a strong foundation for implementing STI PrEP.

Abstract Background Girls exposed to violence have a high risk of being victimized as adults and are more likely than non-abused women to have children who are treated violently. This intergenerational transmission may be especially serious when women suffer violence during pregnancy and early motherhood, as it impairs maternal wellbeing and infant health and development. This study examined the intergenerational effects of being exposed to childhood maltreatment (CM) and prenatal intimate partner violence (p-IPV) on perinatal mental distress and birth outcomes in central Vietnam. Methods A birth cohort study in Hue City, Vietnam was conducted with 150 women in the third trimester of pregnancy (Wave 1) and 3 months after childbirth (Wave 2). Using multivariable logistic regression models, augmented inverse-probability-weighted estimators and structural equation modelling (SEM), we analyzed a theoretical model by evaluating adjusted risk differences and pathways between CM, p-IPV and subsequent perinatal adversity and indicators of infant health problems. Results One in two pregnant women experienced at least one form of CM (55.03%) and one in ten pregnant women experienced both CM and p-IPV (10.67%). Mothers who experienced p-IPV or witnessed IPV as a child were approximately twice as likely to experience poor mental health during pregnancy [ARR 1.94, 95% CI (1.20–3.15)]. Infants had a two-fold higher risk of adverse birth outcomes (low birth weight, preterm birth, admission to neonatal intensive care) [ARR 2.45 95% CI (1.42, 4.25)] if their mothers experienced any form of p-IPV, with greater risk if their mothers were exposed to both CM and p-IPV [ARR 3.45 95% CI (1.40, 8.53)]. Notably, significant pathways to p-IPV were found via adverse childhood experience (ACE) events (β = 0.13), neighborhood disorder (β = 0.14) and partner support (β = − 1.3). Conclusion These results emphasize the detrimental and prolonged nature of the effect of violence during childhood and pregnancy. Exposure to childhood maltreatment and violence during pregnancy increases the risk of maternal mental health difficulties and adverse birth outcomes. Antenatal care systems need to be responsive to women’s previous experiences of violence and maternal mental health. The significant protective role of partner support and social support should also be considered when designing tailored interventions to address violence during pregnancy.

Heavy alcohol drinking dysregulates lipid metabolism, promoting hepatic steatosis – the first stage of alcohol-related liver disease (ALD). The molecular circadian clock plays a major role in synchronizing daily rhythms in behavior and metabolism and clock disruption can cause pathology, including liver disease. Previous studies indicate that alcohol consumption alters liver clock function, but the impact alcohol or clock disruption, or both have on the temporal control of hepatic lipid metabolism and injury remains unclear. Here, we undertook studies to determine whether genetic disruption of the liver clock exacerbates alterations in lipid metabolism and worsens steatosis in alcohol-fed mice. To address this question, male liver-specific Bmal1 knockout (LKO) and flox/flox (Fl/Fl) control mice were fed a control or alcohol-containing diet for 5 weeks. Alcohol significantly dampened diurnal rhythms of mRNA levels in clock genes Bmal1 and Dbp, phase advanced Nr1d1/REV-ERBα, and induced arrhythmicity in Clock, Noct, and Nfil3/E4BP4, with further disruption in livers of LKO mice. Alcohol-fed LKO mice exhibited higher plasma triglyceride (TG) and different time-of-day patterns of hepatic TG and macrosteatosis, with elevated levels of small droplet macrosteatosis compared to alcohol-fed Fl/Fl mice. Diurnal rhythms in mRNA levels of lipid metabolism transcription factors (Srebf1, Nr1h2, and Ppara) were significantly altered by alcohol and clock disruption. Alcohol and/or clock disruption significantly altered diurnal rhythms in mRNA levels of fatty acid (FA) synthesis and oxidation (Acaca/b, Mlycd, Cpt1a, Fasn, Elovl5/6, and Fads1/2), TG turnover (Gpat1, Agpat1/2, Lpin1/2, Dgat2, and Pnpla2/3), and lipid droplet (Plin2/5, Lipe, Mgll, and Abdh5) genes, along with protein abundances of p-ACC, MCD, and FASN. Lipidomics analyses showed that alcohol, clock disruption, or both significantly altered FA saturation and remodeled the FA composition of the hepatic TG pool, with higher percentages of several long and very long chain FA in livers of alcohol-fed LKO mice. In conclusion, these results show that the liver clock is important for maintaining temporal control of hepatic lipid metabolism and that disrupting the liver clock exacerbates alcohol-related hepatic steatosis.

A pulse generator using an avalanche transistor operating in current-mode second breakdown driving a 780 nm laser diode is reported. The laser diode is mounted on the skull of a mouse and used in transcranial infrared light stimulation (TILS) experiments. The output current pulse width is approximately 2 ns in an attempt to generate a true impulse-like optical pulse excitation for the TILS experiments.

Abstract Background Accumulating evidence indicate that circulating microRNAs (miRNAs) are useful independent non-invasive biomarkers, with unique miRNA signatures defined for various pathophysiological conditions. However, there are no established universal housekeeping miRNAs for the normalisation of miRNAs in body fluids. We have previously identified an oestrogen-responsive miRNA, miR-494, in regulating the anticoagulant, Protein S, in HuH-7 liver cells. Moreover, increased thrombotic risk associated with elevated circulating oestrogen levels is frequently observed in pregnant women and oral contraceptive users. In order to identify other oestrogen-responsive miRNAs, including miR-494, that may be indicative of increased thrombotic risk in plasma, we used nanoString analysis to identify robust and stable endogenous reference miRNAs for the study of oestrogen-responsive miRNAs in plasma. Results We compared the plasma miRNA expression profile of individuals with: (1) Low circulating oestrogens (healthy men and non-pregnant women not taking oral contraceptives), (2) High circulating synthetic oestrogens, (women taking oral contraceptives) and (3) High circulating natural oestrogens (pregnant females >14 weeks gestation). From the nanoString analyses, 11 candidate reference miRNAs which exhibited high counts and not significantly differentially expressed between groups were selected for validation using realtime quantitative polymerase chain reaction (RT-qPCR) and digital droplet PCR (DDPCR) in pooled plasma samples, and the stability of their expression evaluated using NormFinder and BestKeeper algorithms. Four miRNAs (miR-25-5p, miR-188-5p, miR-222-3p and miR-520f) demonstrated detectable stable expression between groups and were further analysed by RT-qPCR in individual plasma samples, where miR-188-5p and miR-222-3p expression were identified as a stable pair of reference genes. The miRNA reference panel consisting of synthetic spike-ins cel-miR-39 and ath-miR159a, and reference miRNAs, miR-188-5p and miR-222-3p was useful in evaluating fold-change of the pregnancy-associated miRNA, miR-141-3p, between groups. Conclusion The miRNA reference panel will be useful for normalising qPCR data comparing miRNA expression between men and women, non-pregnant and pregnant females, and the potential effects of endogenous and synthetic oestrogens on plasma miRNA expression.

Math heals: Using computational methods to improve design of wound healing assay Cell motility is a central process in wound healing and relies on complex cell-cell interactions. A team of mathematicians led by Ruth Baker and Kit Yates at the University of Oxford utilised computer simulations to re-design wound-healing assays that efficiently identify cell motility parameters. New experimental designs through computer simulation can more accurately identify cell motility parameters by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental replicates. The results describe time and cost-saving alterations for an experimental method for evaluate complex cell-cell interactions.

Modification of the host lipidome via secreted enzymes is an integral, but often overlooked aspect of bacterial pathogenesis. In the current era of prevalent antibiotic resistance, knowledge regarding critical host pathogen lipid interactions has the potential for use in developing novel antibacterial agents. While most studies to date on this matter have focused on specific lipids, or select lipid classes, this provides an incomplete picture. Modern methods of untargeted lipidomics have the capacity to overcome these gaps in knowledge and provide a comprehensive understanding of the role of lipid metabolism in the pathogenesis of infections. In an attempt to determine the role of lipid modifying enzymes produced by staphylococci, we exposed bovine heart lipids, a standardized model for the mammalian lipidome, to spent medium from staphylococcal cultures, and analyzed lipid molecular changes by MS/MSALL shotgun lipidomics. We elucidate distinct effects of different staphylococcal isolates, including 4 clinical isolates of the pathogenic species Staphylococcus aureus, a clinical isolate of the normally commensal species S. epidermidis, and the non-pathogenic species S. carnosus. Two highly virulent strains of S. aureus had a more profound effect on mammalian lipids and modified more lipid classes than the other staphylococcal strains. Our studies demonstrate the utility of the applied untargeted lipidomics methodology to profile lipid changes induced by different bacterial secretomes. Finally, we demonstrate the promise of this lipidomics approach in assessing the specificity of bacterial enzymes for mammalian lipid classes. Our data suggests that there may be a correlation between the bacterial expression of lipid-modifying enzymes and virulence, and could facilitate the guided discovery of lipid pathways required for bacterial infections caused by S. aureus and thereby provide insights into the generation of novel antibacterial agents.

Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP). This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis), platelet response (platelet count >50 × 109 per litre), and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintainedwith stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home) throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.