Project description:Background/aimsPost-operative ileus (POI) is a common complication of abdominal surgery. DA-9701, an extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that also alleviates visceral pain. The aim of this study was to investigate whether DA-9701 can ameliorate POI in rats.MethodsA total of 32 rats were divided into 4 groups: no surgery/no medication (NSNM), no surgery/medication (NSM), surgery/no medication (SNM), and surgery/medication (SM). Gastrointestinal transit (GIT), which is assessed by migration of charcoal, and cumulative stool weight were measured at 24 hours after surgery.ResultsGIT was significantly more delayed in the SNM group than in the other groups (SNM vs NSNM, P < 0.001; SNM vs NSM, P < 0.001; SNM vs SM, P = 0.005). Cumulative stool weight in that group was also lower than in the no surgery groups (SNM vs NSNM, P = 0.007; SNM vs NSM, P = 0.033), and there was no significant difference between the SM group and the no surgery groups (SM vs NSM, P = 0.703; SM vs NSNM, P = 0.347).ConclusionDA-9701 can ameliorate POI by reducing delayed GIT and improving defecation in a rat model of POI.
Project description:Background/aimsThe effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Westerncountries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD.MethodsIn this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. Theprimary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks.ResultsThe global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptomimprovement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups.Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes anddyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups.ConclusionsDA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacyof DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 andpantoprazole in patients with FD.
Project description:BackgroundImproving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI).MethodsForty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal.ResultsChanges in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures).ConclusionOur results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted.Trial registrationClinicalTrials.gov NCT02091635.
Project description:ImportanceStrabismus is a binocular vision disorder characterized by the partial or complete inability to maintain eye alignment on the object that is the target of fixation, usually accompanied by suppression of the deviating eye and consequent 2-dimensional monocular vision. This cue has been used to infer the presence of strabismus in a substantial number of famous artists.ObjectiveTo provide evidence that Leonardo da Vinci had strabismus.Design, setting, and participantsIn exotropia, the divergent eye alignment is typically manifested as an outward shift in the locations of the pupils within the eyelid aperture. The condition was assessed by fitting circles and ellipses to the pupils, irises, and eyelid apertures images identified as portraits of Leonardo da Vinci and measuring their relative positions.Main outcomes and measuresGeometric angle of alignment of depicted eyes.ResultsThis study assesses 6 candidate images, including 2 sculptures, 2 oil paintings, and 2 drawings. The mean relative alignments of the pupils in the eyelid apertures (where divergence is indicated by negative numbers) showed estimates of -13.2° in David, -8.6° in Salvator Mundi, -9.1° in Young John the Baptist, -12.5° in Young Warrior, 5.9° in Vitruvian Man, and -8.3° in an elderly self-portrait. These findings are consistent with exotropia (t5 = 2.69; P = .04, 2-tailed).Conclusions and relevanceThe weight of converging evidence leads to the suggestion that da Vinci had intermittent exotropia with the resulting ability to switch to monocular vision, which would perhaps explain his great facility for depicting the 3-dimensional solidity of faces and objects in the world and the distant depth-recession of mountainous scenes.
Project description:Bowel sound (BS) is receiving more attention as an indicator of gut health since it can be acquired non-invasively. Current gut health diagnostic tests require special devices that are limited to hospital settings. This study aimed to develop a prototype smartphone application that can record BS using built-in microphones and automatically analyze the sounds. Using smartphones, we collected BSs from 100 participants (age 37.6 ± 9.7). During screening and annotation, we obtained 5929 BS segments. Based on the annotated recordings, we developed and compared two BS recognition models: CNN and LSTM. Our CNN model could detect BSs with an accuracy of 88.9% andan F measure of 72.3% using cross evaluation, thus displaying better performance than the LSTM model (82.4% accuracy and 65.8% F measure using cross validation). Furthermore, the BS to sound interval, which indicates a bowel motility, predicted by the CNN model correlated to over 98% with manual labels. Using built-in smartphone microphones, we constructed a CNN model that can recognize BSs with moderate accuracy, thus providing a putative non-invasive tool for conveniently determining gut health and demonstrating the potential of automated BS research.
Project description:Tristan da Cunha is assumed to be the youngest subaerial expression of the Walvis Ridge hot spot. Based on new hydroacoustic data, we propose that the most recent hot spot volcanic activity occurs west of the island. We surveyed relatively young intraplate volcanic fields and scattered, probably monogenetic, submarine volcanoes with multibeam echosounders and sub-bottom profilers. Structural and zonal GIS analysis of bathymetric and backscatter results, based on habitat mapping algorithms to discriminate seafloor features, revealed numerous previously-unknown volcanic structures. South of Tristan da Cunha, we discovered two large seamounts. One of them, Isolde Seamount, is most likely the source of a 2004 submarine eruption known from a pumice stranding event and seismological analysis. An oceanic core complex, identified at the intersection of the Tristan da Cunha Transform and Fracture Zone System with the Mid-Atlantic Ridge, might indicate reduced magma supply and, therefore, weak plume-ridge interaction at present times.
Project description:Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.
Project description:BACKGROUND:Intestinal transplantation provokes an intense inflammatory response within the graft muscularis that causes intestinal ileus. We hypothesised that endogenously produced anti-inflammatory substances could be utilised as novel therapeutics. Therefore, we tested the protective effects of inhaled carbon monoxide (CO) and an endogenous haeme oxygenase 1 (HO-1) anti-inflammatory mediator on transplant induced inflammatory responses and intestinal ileus in the rat. METHODS:Gastrointestinal transit of non-absorbable FITC labelled dextran and in vitro jejunal circular muscle contractions were measured in controls and syngeneic orthotopic transplanted animals with and without CO inhalation (250 ppm for 25 hours). Inflammatory mRNAs for interleukin (IL)-6, IL-1beta, tumour necrosis factor alpha (TNF-alpha), intercellular adhesion molecule 1 (ICAM-1), inducible nitric oxide (iNOS), cyclooxygenase 2 (COX-2), and IL-10 were quantified by real time reverse transcriptase-polymerase chain reaction and HO-1 by northern blot. Histochemical stains characterised neutrophil infiltration and enterocyte apoptosis. RESULTS:Transplantation delayed transit and suppressed jejunal circular muscle contractility. Transplantation induced dysmotility was significantly improved by CO inhalation. Transplantation initiated a significant upregulation in IL-6, IL-1beta, TNF-alpha, ICAM-1, iNOS, COX-2, and HO-1 mRNAs with the graft muscularis. CO inhalation significantly decreased expression of IL-6, IL-1beta, iNOS, and COX-2 mRNAs. CO also significantly decreased serum nitrite levels (iNOS activity). CONCLUSIONS:CO inhalation significantly improved post-transplant motility and attenuated the inflammatory cytokine milieu in the syngeneic rat transplant model. Thus clinically providing CO, the end product of the anti-inflammatory HO-1 pathway, may prove to be an effective therapeutic adjunct for clinical small bowel transplantation.