Injury, inflammation, or resection of the small intestine results in severe compromise of intestinal function. Nevertheless, therapeutic strategies for enhancing growth and repair of the intestinal mucosal epithelium are currently not available. We demonstrate that nude mice bearing subcutaneous proglucagon-producing tumors exhibit marked proliferation of the small intestinal epithelium. The factor responsible for inducing intestinal proliferation was identified as glucagon-like peptide 2 (GLP-2), a 33-aa peptide with no previously ascribed biological function. GLP-2 stimulated crypt cell proliferation and consistently induced a marked increase in bowel weight and villus growth of the jejunum and ileum that was evident within 4 days after initiation of GLP-2 administration. These observations define a novel biological role for GLP-2 as an intestinal-derived peptide stimulator of small bowel epithelial proliferation.

Opioid misuse and dependence among prescription opioid patients in the United States may be higher than expected. A small number of factors, many documented in the medical record, predicted opioid dependence among the out-patients studied. These preliminary findings should be useful in future research efforts.

ObjectiveThe study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD) among outpatients at risk for PTSD.MethodsDiagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080), COMT (rs4680), CHRNA5 (rs16969968), and CRHR1 (rs110402) single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD.ResultsIn bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0–6, mean count = 2.92, standard deviation = 1.36) was associated with lifetime (t [409] = 3.430, P = 0.001) and early onset PTSD (t [409] = 4.239, P = 0.000028). In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158) and early onset PTSD (odds ratio = 2.36, P = 0.000093). Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count × high trauma, P = 0.026) and early onset PTSD (allele count × high trauma, P = 0.016) in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history.ConclusionA cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure interacts with risk allele count, such that PTSD is increased in those with higher risk allele counts and higher trauma exposures. Since the single nucleotide polymorphisms studied encompass stress circuitry and addiction biology, these findings may have implications for neuropsychiatric research and treatment.

The authors estimated the prevalence of lifetime prescription opioid-use disorder among outpatients on opioid therapy using criteria from both versions 4 and 5 of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Using electronic records from a large health care system, a random sample of outpatients undergoing long-term opioid therapy for non-cancer pain was identified and 705 participants completed diagnostic interviews. The prevalence of lifetime DSM-5 opioid-use disorder among these patients was 34.9% (95% confidence interval [CI] = 30.5?39.5), similar to the prevalence of DSM-4 opioid dependence (35.5%, 95% CI = 31.1?40.2). The Kappa value between DSM-5 and DSM-4 criteria was high (Kappa = 0.873, p < 0.0001). Logistic regressions suggested DSM-5 opioid-use disorder was associated with age younger than 65 (odds ratio [OR] = 2.25, p = 0.009), history of opioid abuse (OR = 4.94, p < 0.001), higher opioid withdrawal symptoms (OR = 3.01, p = 0.008), and history of substance abuse treatment (OR = 1.62, p = 0.015), similar to DSM-4. Based on DSM-5, 21.7% of patients met criteria for moderate and 13.2% for severe opioid-use disorder, respectively. Given the changes proposed, the finding that the prevalence of and risk factors for DSM-5 opioid-use disorders were similar to DSM-4 were unexpected. Further research is advised.