The Royal Devon and Exeter Hospital (commonly referred to as RD&E), is a large teaching hospital situated in Exeter, Devon, England. The hospital has two sites, situated in Wonford and Heavitree, Exeter, and is part of the Royal Devon and Exeter NHS Foundation Trust.The hospital is used for the clinical training of medical students from the University of Plymouth and the University of Exeter.
Background and Hypothesis SETD1A, a histone methyltransferase, is implicated in schizophrenia through rare loss-of-function mutations. While SETD1A regulates gene expression via histone H3K4 methylation, its influence on broader epigenetic dysregulation remains incompletely understood. We explored the hypothesis that SETD1A haploinsufficiency contributes to neurodevelopmental disruptions associated with schizophrenia risk via alterations in DNA methylation.Study Design We profiled DNA methylation in the frontal cortex of Setd1a+/- mice across prenatal and postnatal development using Illumina Mouse Methylation arrays. Differentially methylated positions and regions were identified, and their functional relevance was examined through gene and biological annotation. We integrated these findings with transcriptomic and proteomics datasets, and assessed mitochondrial complex I activity to explore potential downstream functional effects.Study Results Setd1a haploinsufficiency resulted in widespread hypomethylation of genes related to ribosomal function and RNA processing that persisted across all developmental stages. Setd1a-targeted promoter regions and noncoding small nucleolar RNAs were also enriched for differentially methylated sites. Despite the downregulation of mitochondrial gene expression, the same genes were not differentially methylated, and complex I activity in Setd1a+/- mice did not differ significantly from controls. Genes overlapping hypomethylated regions were enriched for common genetic associations with schizophrenia.Conclusions Our findings suggest that SETD1A haploinsufficiency disrupts the epigenetic regulation of ribosomal pathways. These results provide insight into an alternative mechanism through which genetic variation in SETD1A influences developmental and synaptic plasticity, contributing to schizophrenia pathophysiology.
Telomere biology disorders (TBDs) and short telomere syndromes are difficult to diagnose, requiring a combination of clinical acumen, gene variant analysis and ideally, telomere length. Severe phenotypes include the ultra-rare dyskeratosis congenita and related early-onset syndromes. More commonly, TBDs can present in adulthood with single- or multi-system fibrotic disease, apoptotic bone marrow failure or malignancy. In the general population, shorter telomere lengths are associated with chronic inflammation, fibrotic disorders, cardiovascular disease, malignancy and disorders of ageing. Diagnosis and expert multisystem care are important; TBD-related conditions require non-standard treatments, minimising immunosuppression and potentially profibrotic treatments. All too aware of the challenges TBD patients face and the urgent need for coordinated care, the patients group DC Action brought together patients, medical professionals and scientists: the “TeloNet” alliance, to share best practice and develop diagnostic and management pathways. This mini review describes the first TeloNet meeting, summarising current United Kingdom (UK) practice, in the context of global provision, drawing attention to challenges and improvements required for timely diagnosis, coordinated monitoring and care for people living with TBDs. TeloNet is UK-focussed but the challenges described have relevance across disparate nations and healthcare systems. Those with an interest in TBDs are invited to join TeloNet by contacting info@dcaction.org.
Abstract Aim This study aimed to evaluate medical students’ understanding, motivations and perceived barriers to pursuing orthopaedic surgery, and to compare differences between male and female delegates attending a regional student-led orthopaedic conference. Method A pre- and post-conference questionnaire was distributed to delegates attending the South West Orthopaedic Conference (SWOC). The survey comprised three domains: (1) understanding of orthopaedics, (2) motivating factors and (3) barriers to pursuing the specialty. Responses were recorded on a Likert scale. The Mann–Whitney U test was used to assess gender-related differences in pre-conference perceptions, and the Wilcoxon signed-rank test was used to analyse paired pre–post changes in understanding. Results Sixty-six delegates (36 male, 30 female) completed the questionnaires. The most frequently reported barriers were lack of undergraduate exposure and limited patient contact, both endorsed at high rates and showing no significant gender difference (p>0.05). Female delegates more often cited work–life balance, availability of role models and training duration as barriers, whereas salary appeared a stronger motivating factor among male delegates (p<0.05). Post-conference responses showed significant improvements in understanding across most orthopaedic knowledge domains (p<0.05), indicating that structured educational events enhance clarity around orthopaedic roles, training and subspecialties. Delegates also reported increased confidence engaging with the specialty following hands-on workshops. Conclusions Insufficient undergraduate exposure and limited patient contact remain prominent barriers to pursuing orthopaedics across genders. Student-led conferences such as SWOC appear effective in improving understanding and stimulating interest in the specialty. Expanding undergraduate orthopaedic exposure may therefore support future recruitment into orthopaedics.
