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BackgroundSocial prescribing interventions connect mental health service users to community resources, to support physical and mental wellbeing and promote recovery. COVID-19 restrictions impacted the delivery of socially prescribed activities, preventing face to face contact for long periods.AimsThe aim of this study was to understand how Voluntary Community and Social Enterprise (VCSE) organisations working with a local NHS mental health Trust responded to the challenges of social distancing during the COVID-19 pandemic. This understanding will be used to make recommendations for future practice, post-lockdown.MethodsUsing a convergent mixed methods design, we surveyed VCSE providers of socially prescribed activities intended to be accessible and appropriate for people with severe mental health needs. Follow-up interviews explored further how they adapted during the first year of the pandemic, the challenges they faced, and how they sought to overcome them. The survey and interview data were analysed separately and then compared to identify convergent and divergent findings.ResultsTwenty VCSE representatives completed the survey which provided a snapshot of changes in levels of connection and numbers reached during lockdown. Of 20 survey respondents, 11 participated in follow-up interviews. Interviews revealed that lockdown necessitated rapid change and responsive adaptation; activities were limited by resource, funding, safeguarding and government restrictions; no single format suited all group members; connection was key; and impact was difficult to gauge.ConclusionsVCSE organisations commissioned to deliver creative socially prescribed activities during the pandemic rapidly adapted their offer to comply with government restrictions. Responsive changes were made, and new knowledge and skills were gained. Drawing on experiences during lockdown, VCSE organisations should develop bespoke knowledge, skills and practices to engage service users in future hybrid delivery of arts, sports, cultural and creative community activities, and to ensure that digital activities offer an equivalent degree of connection to face-to-face ones. Additionally, more effective methods of gaining feedback about patient experience of hybrid delivery is needed.

BackgroundEnteropathogenic (EPEC) and Enteroaggregative (EAEC) E. coli have similar, but distinct clinical symptoms and modes of pathogenesis. Nevertheless when they infect the gastrointestinal tract, it is thought that their flagellin causes IL-8 release leading to neutrophil recruitment and gastroenteritis. However, this may not be the whole story as the effect of bacterial adherence to IEC innate response(s) remains unclear. Therefore, we have characterized which bacterial motifs contribute to the innate epithelial response to EPEC and EAEC, using a range of EPEC and EAEC isogenic mutant strains.MethodologyCaco-2 and HEp-2 cell lines were exposed to prototypical EPEC strain E2348/69 or EAEC strain O42, in addition to a range of isogenic mutant strains. E69 [LPS, non-motile, non-adherent, type three secretion system (TTSS) negative, signalling negative] or O42 [non-motile, non-adherent]. IL-8 and CCL20 protein secretion was measured. Bacterial surface structures were assessed by negative staining Transmission Electron Microscopy. The Fluorescent-actin staining test was carried out to determine bacterial adherence.ResultsPrevious studies have reported a balance between the host pro-inflammatory response and microbial suppression of this response. In our system an overall balance towards the host pro-inflammatory response is seen with the E69 WT and to a greater extent O42 WT, which is in fit with clinical symptoms. On removal of the external EPEC structures flagella, LPS, BFP, EspA and EspC; and EAEC flagella and AAF, the host inflammatory response is reduced. However, removal of E69 lymphostatin increases the host inflammatory response suggesting involvement in the bacterial mediated anti-inflammatory response.ConclusionEpithelial responses were due to combinations of bacterial agonists, with host-bacterial contact a key determinant of these innate responses. Host epithelial recognition was offset by the microbe's ability to down-regulate the inflammatory response. Understanding the complexity of this host-microbial balance will contribute to improved vaccine design for infectious gastroenteritis.

BackgroundCampylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought.MethodologyHealthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1β and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFNγ, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay.ConclusionsBoth innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni.