BACKGROUND & AIMS Early adverse life events (EALs) are associated with irritable bowel syndrome (IBS). Exposure to EALs as assessed by the Adverse Childhood Experiences (ACE) questionnaire is associated with greater disease prevalence, but ACE has not been studied in gastrointestinal disorders. Study aims were to: 1) Estimate the prevalence of EALs in the IBS patients using the ACE questionnaire; 2) Determine correlations between ACE and Early Trauma Inventory Self Report-Short Form (ETI-SR) scores to confirm its validity in IBS; and 3) Correlate ACE scores with IBS symptom severity. METHODS 148 IBS (73% women, mean age=31 years) and 154 HCs (59% women, mean age=30 years) completed the ACE and ETI-SR between June 2010 and April 2015. These surveys measured EALs before age 18 in the domains of physical, sexual, emotional abuse, and general trauma. IBS and abdominal pain severity was measured by a 20-point scale (0=none, 20=worst symptoms). RESULTS The ACE score increased the odds of having IBS (odds ratio (OR)=2.05 [95% confidence interval (CI): 1.21-3.48], p=0.008). Household mental illness (p<0.001), emotional abuse (p=0.004), and incarcerated household member (p=0.019) were significant predictors of IBS. ACE and ETI-SR scores were strongly correlated (r=0.59, p<0.001). ACE, but not ETI-SR, modestly correlated with IBS severity (r=0.17, p=0.036) and abdominal pain (r=0.20, p=0.015). CONCLUSION The ACE questionnaire is a useful instrument to measure EALs in IBS based on its use in large studies, its ability to measure prevalence across different EAL domains, and its correlation with symptom severity.

Background: Irritable bowel syndrome (IBS) is a stress-sensitive disorder associated

IntroductionRecombinant bone morphogenic proteins (BMPs) have shown promise in enhancing in vivo bone formation but have been limited by suboptimal delivery methods. Gene therapy utilizing viral vectors has been proposed as a vehicle for BMP delivery. Previous work has demonstrated the capacity of a BMP-containing lentiviral vector (LV-BMP) to stimulate bone formation in the muscle pouch of a SCID mouse. This study compares the efficacy of BMP-containing adenovirus (Ad-BMP) and LV-BMP vectors in healing a critically sized rat femoral defect.MethodsA critically sized femoral defect was created in the hind limb of 20 Lewis rats. Rat bone marrow cells (RBMCs) co-transfected with Ad-BMP and Ad-luciferase (Ad-luc) were seeded onto a collagen sponge and implanted in the femoral defect of 10 animals (group AV). RBMCs co-transfected with LV-BMP and LV-luc were implanted in the hind limb of 10 animals (group LV). Luciferase expression was assessed using cooled charge coupled device (CCCD) imaging at 3 days and weekly thereafter for 8 weeks. Radiographs were taken at 4 weeks and 8 weeks. Animals were sacrificed at 8 weeks and their femurs were harvested for histological, histomorphometrical, micro CT, and biomechanical analysis.ResultsPreliminary data demonstrate that luciferase expression and bone healing were present in both groups. Luciferase expression in group LV was detected at 8 weeks postoperatively while expression in group AV routinely ceased by 3 weeks. Both vectors induced bone union by 8 weeks; however, this healing was more frequent in group LV (10/10 animals) as compared to group AV (7/10 animals). Femurs harvested from group LV demonstrated improved structural properties including energy to failure (LV: 2.018, Ad: 1.343 NΣmΣdeg), stiffness (LV: 0.076, Ad: 0.056 NΣm/deg; p < .05), maximum torque (LV: 0.363, Ad: 0.293 NΣm), and degree to failure (LV: 8.14, Ad: 7.08 deg). Micro CT analysis showed a statistically significant higher proportion of bone volume to total volume (BV/TV) in group LV versus group AV.ConclusionRBMCs transfected with LV-BMP are more effective at healing a critical size rat femoral defect than Ad-BMP. Luciferase expression was noted at a later time point for those animals in group LV compared to group AV. Gene therapy using a LV vector is a novel and efficient technique for the delivery of osteoinductive growth factor BMP to a site of significant bone loss associated with trauma, revision joint arthroplasty, pseudoarthrosis of the spine, and tumor resection.