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Objective: The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample., Design: Cross-sectional study., Setting: Community-dwelling cohort., Participants: Twins from the TwinsUK cohort PRIMARY AND SECONDARY OUTCOME MEASURES: We compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing., Results: In N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance., Conclusion: Our findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Meiotic recombination is a fundamental process that generates genetic diversity by creating new combinations of existing alleles. Although human crossovers have been studied at the pedigree, population and single-cell level, the more frequent non-crossover events that lead to gene conversion are harder to study, particularly at the individual level. Here we show that single high-fidelity long sequencing reads from sperm can capture both crossovers and non-crossovers, allowing effectively arbitrary sample sizes for analysis from one male. Using fifteen sperm samples from thirteen donors we demonstrate variation between and within donors for the rates of different types of recombination. Intriguingly, we observe a tendency for non-crossover gene conversions to occur upstream of nearby PRDM9 binding sites, whereas crossover locations have a slight downstream bias. We further provide evidence for two distinct non-crossover processes. One gives rise to the vast majority of non-crossovers with mean conversion tract length under 50bp, which we suggest is an outcome of standard PRDM9-induced meiotic recombination. In contrast ~2% of non-crossovers have much longer mean tract length, and potentially originate from the same process as complex events with more than two haplotype switches, which is not associated with PRDM9 binding sites and is also seen in somatic cells., Competing Interests: Competing interests S.Lee is a shareholder and an employee at Pacific Biosciences. P.J.C. is a co-founder, shareholder, and consultant for Quotient Therapeutics. R.S is a consultant to MyHeritage Ltd.

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292., (© 2024. The Author(s).)

Across the globe, student champions are building the social prescribing student movement. Given the numerous linkages between social prescribing and students, there is a need to understand the extent and type of evidence on social prescribing and students. Doing so will address an important gap in the literature, as there are no evidence reviews on this topic. Thus, this scoping review aims to understand the extent and type of evidence on social prescribing and students. This review will be conducted in accordance with the JBI methodology for scoping reviews and will be reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The search strategy will aim to locate both published and unpublished literature. No language or date restrictions will be placed on the search. The databases to be searched include MEDLINE (Ovid), CINAHL (EBSCO), Embase (Ovid), PsycINFO (Ovid), AMED (Ovid), ASSIA (ProQuest), Sociological Abstracts (ProQuest), Global Health (Ovid), Web of Science (Clarivate), Epistemonikos, JBI EBP Database (Ovid), and Cochrane Library. Sources of gray literature to be searched include Google, Google Scholar, Social Care Online (Social Care Institute for Excellence), SIREN Evidence and Resource Library (Social Interventions Research and Evaluation Network), and websites of social prescribing organizations and networks. Additionally, a request for evidence sources will be sent out to members of the Global Social Prescribing Student Council. Two independent reviewers will perform title and abstract screening, retrieval and assessment of full-text evidence sources, and data extraction. Data analysis will consist of basic descriptive analysis. Results will be presented in tabular and/or diagrammatic format alongside a narrative summary., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Muhl et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain., Subjects/methods: In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry., Results: Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 × 10 -6 ), obesity status (P = 4.81 × 10 -5 ), higher serum fasting insulin (P = 5.32 × 10 -4 ), BMI (P = 3.94 × 10 -4 ), and lower serum HDL levels (P = 1.92 × 10 -7 ). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells (P = 4.25 × 10 -4 ) and higher proportion of macrophages (P = 2.74 × 10 -5 ). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression., Conclusions: Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19., (© 2022. The Author(s).)