To evaluate the effect of gastric distension, induced using a gastric \'barostat\', on the secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the presence and absence of small intestinal nutrients in healthy individuals.
Eight healthy participants (two females, six males, mean age 69.3 ± 1.2 years, body mass index 23.5 ± 0.8 kg/m2 ) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure.
Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP-1 with or without gastric distension (P = 1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension (P = 1.00 for saline infusion and P = .99 for glucose infusion).
Gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans.

Consistent buckling distortions of a large membrane patch (200 × 200 Å) are observed during molecular dynamics (MD) simulations using the Monte-Carlo (MC) barostat in combination with a hard Lennard-Jones (LJ) cutoff. The buckling behavior is independent of both the simulation engine and the force field but requires the MC barostat-hard LJ cutoff combination. Similar simulations of a smaller patch (90 × 90 Å) do not show buckling, but do show a small, systematic reduction in the surface area accompanied by ~1 Å thickening suggestive of compression. We show that a mismatch in the way potentials and forces are handled in the dynamical equations versus the MC barostat results in a compressive load on the membrane. Moreover, a straightforward application of elasticity theory reveals that a minimal compression of the linear dimensions of the membrane, inversely proportional to the edge length, is required for buckling, explaining this differential behavior. We recommend always using LJ force or potential-switching when the MC barostat is employed to avoid undesirable membrane deformations.

One of the most investigated properties of porous crystalline metal-organic frameworks (MOFs) is their potential flexibility to undergo large changes in unit cell size upon guest adsorption or other stimuli, referred to as \"breathing\". Computationally, such phase transitions are usually investigated using periodic boundary conditions, where the system\'s volume can be controlled directly. However, we have recently shown that important aspects like the formation of a moving interface between the open and the closed pore form or the free energy barrier of the first-order phase transition and its size effects can best be investigated using non-periodic nanocrystallite (NC) models [Keupp et al. (Adv. Theory Simul., 2019, 2, 1900117)]. In this case, the application of pressure is not straightforward, and a distance constraint was used to mimic a mechanical strain enforcing the reaction coordinate. In contrast to this prior work, a mediating particle bath is used here to exert an isotropic hydrostatic pressure on the MOF nanocrystallites. The approach is inspired by the mercury nanoporosimetry used to compress flexible MOF powders. For such a mediating medium, parameters are presented that require a reasonable additional numerical effort and avoid unwanted diffusion of bath particles into the MOF pores. As a proof-of-concept, NCs of pillared-layer MOFs with different linkers and sizes are studied concerning their response to external pressure exerted by the bath. By this approach, an isotropic pressure on the NC can be applied in analogy to corresponding periodic simulations, without any bias for a specific mechanism. This allows a more realistic investigation of the breathing phase transformation of a MOF NC and further bridges the gap between experiment and simulation.

BACKGROUND: Gastric accommodation is an essential gastric motor function which occurs following ingestion of a meal. Impaired gastric fundic accommodation (IFA) is associated with dyspeptic symptoms. Gastric accommodation is mediated by the vagal pathway with several important physiologic factors such as duodenal nutrient feedback playing a significant role. IFA has been described as a pathophysiologic factor in several gastrointestinal disorders including functional dyspepsia, diabetic gastropathy, post-Nissen fundoplication, postsurgical gastrectomy, and rumination syndrome. Modalities for gastric accommodation assessment include gastric barostat, intragastric meal distribution via scintigraphy, drinking tests (eg, water load), SPECT, MRI, 2D and 3D ultrasound, and intragastric high-resolution manometry. Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post-meal gastric volume.
OBJECTIVE: Our aim is to provide an overview of the physiology, diagnostic modalities, and therapies for IFA. A literature search was conducted on PubMed, Google Scholar, and other sources to identify relevant studies available until December 2020. Gastric accommodation is an important gastric motor function which if impaired, is associated with several upper gastrointestinal disorders. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing.

BACKGROUND: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D.
METHODS: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of \"responders\" in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron.
CONCLUSIONS: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron\'s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond.
BACKGROUND: ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.

BACKGROUND: Migraine is a condition frequently associated with gastrointestinal disorders. Previous reports have shown the relationship between irritable bowel syndrome and migraine, but no data are yet available in patients with functional dyspepsia. We therefore evaluated whether alteration of gastric sensorimotor activity may be related to migraine.
METHODS: Sixty patients affected by functional dyspepsia, 38 with postprandial distress syndrome and 22 with epigastric pain syndrome were enrolled in a cohort study. Presence and severity of dyspeptic symptoms, migraine presence and severity, gastric sensitivity thresholds during fasting and postprandial period, gastric accommodation and gastric emptying time were evaluated.
RESULTS: In epigastric pain syndrome, 12/22 (54%) patients suffered from migraine and this condition was never correlated with meal ingestion. In postprandial distress syndrome patients, 29/38 (76%) suffered from migraine, in 26/29 (89%) its onset was considered as meal-related, and migraine severity was significantly correlated with postprandial modification of the gastric discomfort threshold (r = -0.73; p < 0.001). In patients with postprandial distress syndrome, in the subgroup with moderate to severe migraine, the severity of fullness and early satiation was significantly higher than in patients with mild or absent migraine. In patients with moderate to severe migraine, gastric accommodation, sensitivity thresholds and gastric emptying time were similar to patients with mild or no migraine.
CONCLUSIONS: In patients with functional dyspepsia and postprandial symptoms, migraine is a very frequent comorbidity. On clinical grounds, it is associated with an increased severity of fullness and early satiation and, on pathophysiological grounds, it seems correlated with postprandial hypersensitivity.

BACKGROUND: The pathophysiology of abdominal distention in irritable bowel syndrome (IBS) is still a matter of debate, but the relationship between modifications of intestinal tone and abdominal volume has never been analyzed.
METHODS: Eighty-four patients affected by IBS and reporting moderate to severe abdominal distention were enrolled. Thirty-nine presented abdominal distention immediately after and forty-five presented abdominal distention independently of meal intake. Twenty healthy volunteers (HV), comparable for gender and age, were also enrolled. All the subjects underwent fasting and postprandial recto-sigmoid volume monitoring with barostat and abdominal girth measurement to evaluate abdominal distention.
RESULTS: In comparison with HV (75±13 mL) and with patients with meal-unrelated abdominal distention (135±56 mL), in the subgroup of patients with severe meal-related abdominal distention recto-sigmoid tone response to the meal was significantly reduced (mean increase of balloon volume 184±89 mL; P<.001), paralleling abdominal girth increase and occurring immediately after test meal intake. Meal-induced abdominal girth modification was significantly correlated with meal-related modification of recto-sigmoid tone (r=.71) and abdominal symptoms.
CONCLUSIONS: In patients with IBS suffering from severe postprandial abdominal distention, a postprandial reduction of intestinal tone is associated with this bothersome symptom. Further studies are needed to evaluate whether drugs acting on the modification of intestinal tone could be useful in the treatment of these patients.

Intestinal microbiota regulates gastrointestinal sensory-motor function. Prebiotics such as arabinoxylan-oligosaccharide (AXOS) are non-digestible, fermentable food ingredients beneficially affecting intestinal microbiota, colon activity, and improving human health. We wanted to investigate whether acute AXOS or maltodextrin (placebo) administration may alter gastric sensitivity (GS), accommodation (GA), nutrient tolerance (NT) in man.
Thirteen HV (6 M, 32.2 ± 1.8 years; BMI 22.3 ± 0.2) underwent two 48 h treatment periods with oral 4 × 9.4 g AXOS or 4 × 10 g maltodextrin (at least 1 week wash-out) for gastric barostat assessment of GS, gastric compliance (GC), GA to a liquid test meal, on day 1, and NT drink test, on day 2. Oro-cecal transit-time (OCTT), colonic fermentation (CF) were assessed simultaneously with (13) C-lactose ureide, H2 breath tests.
Arabinoxylan-oligosaccharide significantly increased CF on day 1 and 2 (565 ± 272 vs 100 ± 24, 365 ± 66 vs 281 ± 25 H2 ppm/min, AXOS vs maltodextrin, both p < 0.05), not the OCTT. AXOS did not alter GC, sensitivity before and after the meal. Gastric accommodation was not significantly influenced by AXOS (volume increment: 171 ± 33 vs 130 ± 28 mL, AXOS vs maltodextrin, p = NS). On day 1, AXOS fermentation was associated with significantly higher postprandial bloating scores (960 ± 235 vs 396 ± 138 mm*min, AXOS vs maltodextrin, p < 0.05). On day 2, AXOS did not affect maximal NT (946 ± 102 vs 894 ± 97 mL, AXOS vs maltodextrin, p = NS), increased the bloating score (1236 ± 339 vs 675 ± 197 mm*min, AXOS vs maltodextrin, p < 0.05).
Acute AXOS administration, associated with increased CF, does not affect GA, is not associated with increased meal-induced satiety or perception scores.

BACKGROUND: Impaired gastric accommodation is one of the major features of functional dyspepsia. Mosapride citrate is a 5-hydroxytryptamine receptor 4 (5-HT4) agonist, which is shown to improve upper abdominal symptoms. However, effect of mosapride on gastric accommodation was not clear. We tested the hypothesis that mosapride enhances the gastric accommodation in normal individuals.
METHODS: Fourteen male healthy volunteers completed this study. Single administration of mosapride or placebo was performed randomly with more than 1-week interval. Subjects swallowed a triple-lumen polyvinyl tube with a polyethylene bag. The bag was positioned in the proximal stomach and the minimal distending pressure (MDP) was determined. The ramp distension starting from the MDP was then performed and subjects were instructed to score their perception using ordinate scales. Next the intra-bag pressure was set at MDP + 2 mmHg and a liquid meal was administered 30 min later, and the intra-bag volume was recorded for 60 min. We compared the MDP, perception scores, and the intra-bag volume changes by administering placebo and mosapride.
RESULTS: Minimal distending pressure was not significantly different in subjects receiving mosapride or placebo. Treatment with mosapride had no effect on intra-bag pressures or volumes inducing first sensation or discomfort. Gastric accommodation, expressed as the difference between pre- and postmeal intra-bag volumes, and the percent change of the intra-bag volumes by the meal was significantly enhanced by mosapride compared with placebo.
CONCLUSIONS: This is the first study clearly demonstrating that single administration of 5-HT4 agonist can enhance gastric accommodation in humans. (Umin.ac.jp, number UMIN000014063).

OBJECTIVE: To investigate the anal sphincter and rectal factors that may be involved in fecal incontinence that develops following fistulotomy (FIAF).
METHODS: Eleven patients with FIAF were compared with 11 patients with idiopathic fecal incontinence and with 11 asymptomatic healthy subjects (HS). All of the study participants underwent anorectal manometry and a barostat study (rectal sensitivity, tone, compliance and capacity). The mean time since surgery was 28 ± 26 mo. The postoperative continence score was 14 ± 2.5 (95%CI: 12.4-15.5, St Mark\'s fecal incontinence grading system).
RESULTS: Compared with the HS, the FIAF patients showed increased rectal tone (42.63 ± 27.69 vs 103.5 ± 51.13, P = 0.002) and less rectal compliance (4.95 ± 3.43 vs 11.77 ± 6.9, P = 0.009). No significant differences were found between the FIAF patients and the HS with respect to the rectal capacity; thresholds for the non-noxious stimuli of first sensation, gas sensation and urge-to-defecate sensation or the noxious stimulus of pain; anal resting pressure or squeeze pressure; or the frequency or percentage of relaxation of the rectoanal inhibitory reflex. No significant differences were found between the FIAF patients and the patients with idiopathic fecal incontinence.
CONCLUSIONS: In patients with FIAF, normal motor anal sphincter function and rectal sensitivity are preserved, but rectal tone and compliance are impaired. The results suggest that FIAF is not due to alterations in rectal sensitivity and that the rectum is more involved than the anal sphincters in the genesis of FIAF.