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The functional integrity of the intestinal epithelial barrier forms a major defense against invading pathogens, including gastrointestinal-dwelling nematodes, which are ubiquitous in their distribution worldwide. Here, we show that an increase in the rate of epithelial cell turnover in the large intestine acts like an \"epithelial escalator\" to expel Trichuris and that the rate of epithelial cell movement is under immune control by the cytokine interleukin-13 and the chemokine CXCL10. This host protective mechanism against intestinal pathogens has implications for our wider understanding of the multifunctional role played by intestinal epithelium in mucosal defense.

Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

The ability of the colon to generate an immune response to pathogens, such as the model pathogen Trichuris muris, is a fundamental and critical defense mechanism. Resistance to T. muris infection is associated with the rapid recruitment of dendritic cells (DCs) to the colonic epithelium via epithelial chemokine production. However, the epithelial–pathogen interactions that drive chemokine production are not known. We addressed the role of the cytosolic pattern recognition receptor Nod2. In response to infection, there was a rapid influx of CD103+CD11c+ DCs into the colonic epithelium in wild-type (WT) mice, whereas this was absent in Nod2−/− animals. In vitro chemotaxis assays and in vivo experiments using bone marrow chimeras of WT mice reconstituted with Nod2−/− bone marrow and infected with T. muris demonstrated that the migratory function of Nod2−/− DCs was normal. Investigation of colonic epithelial cell (CEC) innate responses revealed a significant reduction in epithelial production of the chemokines CCL2 and CCL5 but not CCL20 by Nod2-deficient CECs. Collectively, these data demonstrate the importance of Nod2 in CEC responses to infection and the requirement for functional Nod2 in initiating host epithelial chemokine-mediated responses and subsequent DC recruitment and T-cell responses following infection.

'Oh, and I, like most people, am determined to lose that half a stone I am intending to put on at Christmas.' Big Brother contestant Shell Jubin is determined to give up smoking in the New Year. BEAT 106 DJ Heather Suttie has set herself a real challenge for the New Year. She is putting herself on a strict diet which will cut out many of the foods that have become her staple diet. HIGH HOPES: Shell Jubin and Annemarie Fulton, right; FEELINGFRUITY: A great start

ObjectivesAdults with knee instability related to neuromuscular disorders or central nervous conditions often experience mobility problems and rely on orthoses to improve function and mobility. Patient views of device effectiveness and acceptability are underexplored. Our study aimed to elicit device users’ perspectives regarding fitting, acceptability, effectiveness and use of orthoses, and identify important treatment outcomes.DesignQualitative descriptive study using in-depth semistructured interviews. Interview transcriptions were coded and thematically analysed, using ‘Framework’.Setting and participantsA purposive sample of 24 adult users of orthotic devices. Nineteen patients were recruited across three National Health Service sites, and five people through charities/patient support groups in England. Half of the participants had been diagnosed with poliomyelitis, and the remainder with multiple sclerosis, Charcot-Marie-Tooth disease, spinal injury or spina bifida, and stroke. The median age of participants was 64.5 years (range 36–80 years).ResultsPatients’ medical condition impacted significantly on daily life. Participants relied on orthotic devices to enable engagement in daily activities. Patient goals for mobility were linked to individual circumstances. Desired treatment outcomes included reduction in pain, trips and falls, with improved balance and stability. Effectiveness, reliability, comfort and durability were the most valued features of orthoses and associated with reported use. Obtaining suitable footwear alongside orthotic devices was a significant concern. Time pressures during device fitting were viewed negatively.ConclusionsOrthotic devices for knee instability play a crucial role in promoting, maintaining and enhancing physical and psychological health and well-being, enabling patients to work, engage in family life and enjoy social activities. Future research should consider how best to measure the impact of orthotic devices on patient quality of life and daily functioning outside the clinic setting, as well as device use and any adverse effects.Trial registration numberThis qualitative study was retrospectively registered as Current Controlled Trials ISRCTN65240228.

Children continue to experience harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. The international ISupport collaboration aimed to develop standards to outline and explain good procedural practice and the rights of children within the context of a clinical procedure. The rights-based standards for children undergoing tests, treatments, investigations, examinations and interventions were developed using an iterative, multi-phased, multi-method and multi-stakeholder consensus building approach. This consensus approach used a range of online and face to face methods across three phases to ensure ongoing engagement with multiple stakeholders. The views and perspectives of 203 children and young people, 78 parents and 418 multi-disciplinary professionals gathered over a two year period (2020–2022) informed the development of i nternational rights-based standards for the care of children having tests, treatments, examinations and interventions. The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.     Conclusion : This is the first study of its kind which outlines international rights-based procedural care standards from multi-stakeholder perspectives. The standards offer health professionals and educators clear evidence-based tools to support discussions and practice changes to challenge prevailing assumptions about holding or restraining children and instead encourage a focus on the interests and rights of the child. What is Known: • Children continue to experience short and long-term harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. • Professionals report uncertainty and tensions in applying evidence-based practice to children’s procedural care. What is New: • This is the first study of its kind which has developed international rights-based procedural care standards from multi-stakeholder perspectives. • The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.