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Summary: Background: Delays in Crohn's disease (CD) diagnosis are positively associated with ileal location and an increased risk of complications. Aim: To develop a simple risk assessment tool to enable primary care physicians to recognise potential ileal CD earlier, shortening the delay to specialist investigation Methods: Three cohorts were acquired for this study. Cohort 1 included 61 patients retrospectively identified with ileal CD between 2000 and 2010 and 78 matched controls drawn from a cohort referred for investigation of abdominal symptoms. Cohort 2 included 42 individuals diagnosed with ileal CD and 57 controls identified prospectively. Cohort 3 included an additional 84 individuals with ileal CD and 495 without CD referred for colonoscopy. Clinical symptoms and serological biomarkers were acquired and used to develop a risk prediction algorithm. The algorithm was trained independently on each of the three cohorts and tested on the latter two cohorts. Results: Altered bowel habit with abdominal pain combined with derangements in white cell count (WCC), albumin and platelet counts were important features in predicting ileal CD (AUC = 0.92, 95% CI = 0.89‐0.92). This was validated in cohorts 2 (AUC = 0.96, 95% CI = 0.95‐0.98) and 3 (AUC = 0.94, 95% CI = 0.92‐0.96). C‐reactive protein was independently associated with ileal CD but non‐signficant in a multivariate model. Conclusion: A web‐based risk stratification tool for ileal CD has been developed from objective and symptom‐based criteria. This tool enables primary care physicians to more confidently request urgent specialist assessment for patients identified as at high risk for ileal CD. [ABSTRACT FROM AUTHOR]

[gamma]-Aminobutyric acid (GABA) exerts protective and regenerative effects on mouse islet [beta]-cells. However, in humans it is unknown whether it can increase [beta]-cell mass and improve glucose homeostasis. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-[gamma] mice with streptozotocin-induced diabetes. GABA treatment increased grafted [beta]-cell proliferation, while decreasing apoptosis, leading to enhanced [beta]-cell mass. This was associated with increased circulating human insulin and reduced glucagon levels. Importantly, GABA administration lowered blood glucose levels and improved glucose excursion rates. We investigated GABA receptor expression and signaling mechanisms. In human islets, GABA activated a calcium-dependent signaling pathway through both GABA A receptor and GABA B receptor. This activated the phosphatidylinositol 3-kinase-Akt and CREB-IRS-2 signaling pathways that convey GABA signals responsible for [beta]-cell proliferation and survival. Our findings suggest that GABA regulates human [beta]-cell mass and may be beneficial for the treatment of diabetes or improvement of islet transplantation. [ABSTRACT FROM AUTHOR]