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Sporadic inclusion body myositis (IBM) is the most common acquired muscle disease in adults over age 50, yet it remains unclear whether the disease is primarily driven by T cell–mediated autoimmunity. IBM muscle biopsies display nuclear clearance and cytoplasmic aggregation of TDP-43 in muscle cells, a pathologic finding observed initially in neurodegenerative diseases, where nuclear loss of TDP-43 in neurons causes aberrant RNA splicing. Here, we show that loss of TDP-43–mediated splicing repression, as determined by inclusion of cryptic exons, occurs in skeletal muscle of subjects with IBM. Of 119 muscle biopsies tested, RT-PCR–mediated detection of cryptic exon inclusion was able to diagnose IBM with 84% sensitivity and 99% specificity. To determine the role of T cells in pathogenesis, we generated a xenograft model by transplanting human IBM muscle into the hindlimb of immunodeficient mice. Xenografts from subjects with IBM displayed robust regeneration of human myofibers and recapitulated both inflammatory and degenerative features of the disease. Myofibers in IBM xenografts showed invasion by human, oligoclonal CD8+ T cells and exhibited MHC-I up-regulation, rimmed vacuoles, mitochondrial pathology, p62-positive inclusions, and nuclear clearance and cytoplasmic aggregation of TDP-43, associated with cryptic exon inclusion. Reduction of human T cells within IBM xenografts by treating mice intraperitoneally with anti-CD3 (OKT3) suppressed MHC-I up-regulation. However, rimmed vacuoles and loss of TDP-43 function persisted. These data suggest that T cell depletion does not alter muscle degenerative pathology in IBM.

Background: Annual health checks in primary care include hearing assessment, though current guidance recommends subjective assessment only. Previous studies suggest this is inadequate and recommend objective alternatives such as hearing screening. This study aimed to assess the feasibility of hearing screening and examine the last recorded annual health check outcome for hearing, for those diagnosed with hearing loss as a result of the screening process. Method: Hearing screening took place in four locations and 75 people with learning disabilities participated. Contact was made with each individual's GP to share results and to request onward referral where indicated. Findings: Wax occlusion prevented screening for 23%. Fifty-seven people completed the screen, and 25 had suspected hearing loss. Of these, 22 people required referral to Audiology to verify their hearing thresholds. Only 13 were actually referred, and 11 individuals underwent assessment in Audiology, resulting in 10 being diagnosed with hearing loss. The most recent annual health check outcomes for hearing were examined for those diagnosed with hearing loss. Of the records we accessed, hearing loss had not been identified or actioned in every case. Conclusions: Hearing screening is shown here to be a suitable method for detecting hearing loss. We recommend changing current annual health check practice to incorporate objective screening. Only 12% of those with suspected hearing loss were known to Audiology services, suggesting a substantial proportion of undetected hearing loss in the community. We found evidence of apparent reluctance around referral and hearing aid fitting and make suggestions for improvement.

Background: People with learning disabilities have an increased risk of diabetes, cardiovascular disease and hearing loss. This study explored service users' and health professionals' perspectives and experiences of adopting minimally invasive diagnostic and screening devices, known as point-of-care testing (POCT) as a means of improving access and engagement. Materials and Methods: Focus groups and semi-structured interviews were undertaken with attendees at a nonhealthcare day centre, specialist learning disability clinical network and national leads as well as researchers into learning disability and point-of-care issues. Thematic analysis of the data was undertaken. Results: There was a lack of awareness and experience of POCT across the users and health professionals. Despite this, on seeing the devices and discussing application there was strong support and acceptability across all participants for their use so long as individual needs were addressed. There was no consistent sense of where this testing should be done but support for the flexibility this could provide in terms of nonmedicalised locations and individual needs. Strategies for success included the use of specific adjustments such as the presence of a known carer, pre-testing information in an appropriate format and taking into account each individual's preferences. Conclusions: POCT is considered a viable and useful method for improving access to testing for people with learning disabilities. Adoption barriers in implementation identified as specific to the field of learning disabilities included lack of POCT awareness and diagnostic overshadowing concerns, and adjusting for individualised needs is essential.

Background: Prostate cancer is the most common cancer in the UK and Black African-Caribbean men are twice as likely to develop prostate cancer as white men. These cancer inequalities need urgent tackling. Barriers to early diagnosis are complex and require complex solutions. Culturally-tailored, community-centred and participatory approaches show promise in tackling cancer inequalities. We aim to co-design a culturally appropriate intervention to tackle barriers to early diagnosis of prostate cancer for Black men in Scotland and the North-East of England using a community-centred participatory approach. Methods: The PROCAN-B study is a mixed methods study set in Scotland and the North-East of England. A Public Involvement and Community Engagement (PICE) group (n = 12), is involved at every step of the research. Drawing on principles of the Integrated Screening Action model (I-SAM), the study has 8 objectives: 1) to explore barriers to early diagnosis of prostate cancer among Black men (45+) through focus groups (n = 12); 2) to co-design a culturally acceptable peer-led intervention to tackle barriers to early diagnosis of prostate cancer in Black men; 3) to train members of the community as 'peer-facilitators' (n = 8); 4) to deliver the intervention in each location, facilitated by peer-facilitators, with a purposive sample (n = 20) of Black men (45+); 5) to qualitatively evaluate the intervention through focus groups; 6) to refine the intervention based on qualitative feedback; 7) to pilot the refined intervention with another purposive sample (n = 40) through a cross-sectional survey pre- and post-intervention; 8) to qualitatively evaluate the refined intervention through focus groups to further refine the intervention. Discussion: Community-centred and culturally tailored interventions have potential to be effective in addressing barriers to early diagnosis of prostate cancer, and thus ultimately reduce morbidity and mortality rates through earlier diagnosis in Black communities. [ABSTRACT FROM AUTHOR]