Brian Surjanhata

Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding. Trial Registration ClinicalTrials.Gov NCT02136745

Brain white matter microstructure is associated with susceptibility to motion-induced nausea.

Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of the heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion‐induced nausea are due to microstructural differences in the inferior fronto‐occipital fasciculus (IFOF), the white matter tract connecting the right visual motion processing area (MT+/V5) and right anterior insula. To test this hypothesis, we acquired diffusion tensor imaging data from 30 healthy adults who were subsequently dichotomized into high and low nausea susceptibility groups based on the Motion Sickness Susceptibility Scale. We quantified diffusion along the IFOF for each subject based on axial diffusivity (AD); radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA), and evaluated between‐group differences in these diffusion metrics. Subjects with high susceptibility to nausea rated significantly (P < 0.001) higher nausea intensity to visual motion stimuli and had significantly (P < 0.05) lower AD and MD along the right IFOF compared to subjects with low susceptibility to nausea. This result suggests that differences in white matter microstructure within tracts connecting visual motion and nausea‐processing brain areas may contribute to nausea susceptibility or may have resulted from an increased history of nausea episodes.

Comparative analysis of phase III migrating motor complexes in stomach and small bowel using wireless motility capsule and antroduodenal manometry

Background  Assessment of phase III MMC is often not performed due to the invasive nature of antroduodenal manometry used to detect it. The aim of the study was to evaluate the ability of wireless motility capsule (WMC) to detect phase III MMC and correlate it with the simultaneous measurements by antroduodenal manometry (ADM).

Bear-down maneuver is a useful adjunct in the evaluation of children with chronic constipation.

Background and Objectives: Chronic constipation is a common problem in pediatrics and often the result of obstructed defecation. The aim of this study was to determine the use of the bear-down maneuver (BDM) in the evaluation of children with chronic constipation and to establish optimal conditions for its performance. Methods: This retrospective study compares BDM with balloon expulsion testing (BET) during anorectal manometry in 38 children with chronic constipation. BDM was performed with 0-, 20-, 40-, and 60-mL balloon inflation. BET, performed with a 60-mL balloon, was considered normal if the balloon was expelled within 1 minute. Results: Rectal pressure during BDM was 48% higher in patients able to expel the balloon during BET compared with those who could not (P < 0.05). Anal canal pressure was 46% lower in patients able to expel the balloon (P < 0.05). A rectoanal pressure differential greater than zero during BDM was 90% predictive that the subject would be able to expel the balloon. The optimal balloon inflation volume was 60 mL. Conclusions: BDM using an inflated balloon provides valuable mechanistic information in the evaluation of children with dyssynergic defecation. We found that patients often had either an insufficient rectal pressure during bear-down or an abnormally high anal canal pressure. This information may be useful in planning further treatment for these children.

Small bowel fed response as measured by wireless motility capsule: Comparative analysis in healthy, gastroparetic, and constipated subjects

Small bowel fed response is an increased contractile activity pattern following the ingestion of a meal. Postprandial motility is traditionally evaluated using small bowel manometry. Wireless motility capsule (WMC) is an ingestible wireless capsule that measures pH, temperature, and intraluminal pressure. The primary aim of the study was to assess small bowel fed response captured with the non‐invasive WMC. The secondary aim was to compare the fed response patterns between healthy subjects and patients with motility disorders of gastroparesis and constipation.

Colonic motor response to wakening is blunted in slow transit constipation as detected by wireless motility capsule

Background: Chronic constipation may be categorized as normal transit (NTC), slow transit (STC), or outlet obstruction. Colonic wake response is a relative increase in colonic motility upon awakening. Colonic manometry studies have demonstrated attenuated wake response in STC. We sought to evaluate wake response among healthy (H), NTC, and STC patients using wireless motility capsule (WMC). Methods: A retrospective study of WMC data from a multicenter clinical trial and a tertiary gastroenterology clinic was performed. WMC motility parameters of contraction frequency (Ct) and area under the contraction curve (AUC) were analyzed in 20‐min windows 1‐h before and after awakening. T‐tests compared parameters between H, NTC, and STC. Linear regression analysis was performed to determine if outlet obstruction confounded data. A receiver operating characteristic curve demonstrated optimal Ct cut‐offs to define blunted wake response. Results: A total of 62 H, 53 NTC and 75 STC subjects were analyzed. At 20, 40, and 60 min after awakening, STC subjects had significantly lower mean Ct when compared to H (p < 0.001) and NTC (p < 0.01). Linear regression demonstrated that outlet obstruction was not associated with a decreased wake response (&bgr; = 3.94, (CI ‐3.12–1.00), P = 0.27). Defined at the Ct threshold of 64 at 20‐min post‐wake, blunted wake response sensitivity was 84% and specificity was 32% for chronic constipation. Conclusion: Findings of an impaired wake response in subjects with STC and not NTC adds further evidence to neuronal dysfunction as an etiology of STC, and identifies a possible temporal target for pharmacologic intervention.