Neurogastroenterology and Motility最新文献

{"title":"Methods and Techniques for Closed-Loop Gastrointestinal Pacing.","authors":"Chaveeka Weerakoon, Leo K Cheng, Peng Du, Niranchan Paskaranandavadivel, Nipuni D Nagahawatte","doi":"10.1111/nmo.70467","DOIUrl":"10.1111/nmo.70467","url":null,"abstract":"<p><strong>Purpose: </strong>Gastrointestinal slow waves are rhythmic electrical events that contribute to the coordination of motility. Functional motility disorders such as gastroparesis are linked to abnormal slow wave activity, and current treatments do not target the underlying electrical dysfunction. Gastrointestinal electrical pacing restores normal rhythms, but open-loop pacing lacks adaptation to underlying slow wave activity, leading to reduced energy efficiency and potential overstimulation.</p><p><strong>Methods: </strong>A novel closed-loop pacing system was developed to detect gastric and intestinal slow waves and dynamically pace in response to the underlying rhythm. High-resolution electrode arrays were placed on the serosal surface of anesthetized pigs for simultaneous pacing and mapping. The control strategy comprised two steps: (i) continuous detection and classification of slow waves as normal rhythm (stomach: 15-25 s; small intestine: 3-5 s) or abnormal rhythm; and (ii) pacing delivery and entrainment assessment, with pulses (100-400 ms, 3-8 mA) triggered by abnormal rhythms or failed entrainment.</p><p><strong>Results: </strong>Detection of slow wave events achieved an accuracy of 78% for both the stomach and the small intestine. Entrainment detection yielded an accuracy of 73% for the stomach and 67% for the small intestine. Closed-loop pacing successfully restored abnormal gastric and small intestinal slow wave periods to normal physiological ranges and reduced the number of pulses delivered by 60% compared to open-loop pacing.</p><p><strong>Conclusion: </strong>Closed-loop pacing significantly reduced pulse delivery, demonstrating the feasibility of a targeted, adaptive approach that may reduce pacing burden, although effects on motility and gastric emptying warrant further investigation.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":"e70467"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of Irritable Bowel Syndrome Among Chilean Adults: Differences Across Healthcare Settings and Urban-Rural Populations.","authors":"Christian von Muhlenbrock, Nicole Pacheco, Natalia Santos, Florencia Carbone, Jan Tack, Ana María Madrid, Tim Vanuytsel","doi":"10.1111/nmo.70472","DOIUrl":"https://doi.org/10.1111/nmo.70472","url":null,"abstract":"<p><strong>Introduction: </strong>Irritable bowel syndrome (IBS) is one of the most prevalent disorders of gut-brain interaction (DGBIs), with an estimated global prevalence ranging from 4.1% to 17%. However, prevalence data remain largely unknown in many countries and across different populations.</p><p><strong>Aim: </strong>The aim of this study was to characterize IBS among Chilean adults using Spanish-validated Rome diagnostic criteria across healthcare and community-based settings, including public and private gastroenterology outpatient populations and urban and rural/Mapuche community populations.</p><p><strong>Methods: </strong>IBS was assessed using standardized, Spanish-validated Rome questionnaires, with Rome IV criteria applied to available symptom data in the outpatient cohorts (public and private) and the official Spanish-language Rome IV Diagnostic Questionnaire used in the community-based populations (urban and rural/Mapuche). Data were analyzed using chi-squared, Mann-Whitney U, and multivariable logistic regression, with analyses performed using GraphPad Prism.</p><p><strong>Results: </strong>We evaluated the proportion of gastroenterology outpatients meeting Rome IV criteria for IBS and IBS subtypes in 8717 patients, as well as IBS prevalence in 896 urban and rural/Mapuche community participants. The proportion of gastroenterology outpatients meeting Rome IV criteria for IBS was higher in the public than private hospital (36.2% vs. 23.3%; p < 0.0001) and in urban females versus males (30.5% vs. 20.5%; p = 0.0015). Rural/Mapuche and urban populations showed comparable IBS prevalence (30.9% vs. 25.7%; p = 0.26), and rural/Mapuche residence was not significantly associated with IBS after adjustment for age and sex (adjusted OR 1.18, 95% CI 0.68-2.05; p = 0.56). The rural/Mapuche population had a different subtype distribution, with a higher proportion of IBS-M.</p><p><strong>Conclusions: </strong>IBS symptoms compatible with Rome IV criteria were common across the evaluated Chilean adult populations, with differences observed according to healthcare setting and sex. Although IBS prevalence did not differ significantly between the urban and rural/Mapuche populations, this finding should be interpreted cautiously given differences in age and recruitment methods. Larger population-based studies are needed to confirm these findings in rural and Indigenous populations. These data provide novel insights into IBS epidemiology in a Latin American country with marked socioeconomic heterogeneity and may inform future population-based and mechanistic studies in diverse settings.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Padova Classification After Fundoplication: Robust Diagnostic Performance and the Need for External Validation.","authors":"Amir Mari, Nama Mubariki","doi":"10.1111/nmo.70478","DOIUrl":"https://doi.org/10.1111/nmo.70478","url":null,"abstract":"","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149239115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal Symptom Events and Motility Alterations Associated With GLP-1 Receptor Agonists.","authors":"Julio Zuniga Cisneros, Camille Lupianez-Merly, Saam Dilmaghani, Ryan J Lennon, Sara Then, Phil Fiero, Rob Blundo, Gianrico Farrugia, Michael Camilleri, Madhusudan Grover","doi":"10.1111/nmo.70458","DOIUrl":"https://doi.org/10.1111/nmo.70458","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal symptom events (GISE) are common with glucagon-like peptide-1 receptor agonists (GLP-1RA). We aimed to determine the prevalence of GISE and clinical factors associated with GISE.</p><p><strong>Methods: </strong>An integrated platform database was used to collect real-world data. Using a retrospective cohort study design, Kaplan-Meier analysis was used to estimate GISE-free survival over 60 months. To identify predictors of GISE, the cohort was randomly split 80/20 into training and testing sets. A LASSO-penalized Cox model was used to identify relevant associations, after which main-effect and interaction models were constructed. Gastric emptying scintigraphy (GES) of solids was extracted from electronic medical records, where available.</p><p><strong>Results: </strong>Among 78,277 patients, 87% reported no baseline GI symptoms. At 60 months, 53% reported at least one GISE, most commonly abdominal pain (28%) and nausea (25%). Women were at higher risk of GISE than men (Kaplan-Meier HR 1.4). In the prediction model, baseline diarrhea, constipation, abdominal pain, and nausea were associated with higher GISE risk (HRs 2.2, 2.0, 1.7, and 1.6, respectively), and male sex with lower risk (HR 0.79). Concomitant baseline use of metoclopramide (HR 1.6) was also associated with higher risk of GISE, with weaker associations for tricyclic antidepressants, GABA analogs, and opioids (HRs 1.1-1.2). Model discrimination was modest (C-index 0.64 training, 0.63 testing). Among 696 symptomatic patients clinically referred for GES after GLP-1RA initiation, 34.6% (N = 241) exhibited delayed GE. Constipation was more prevalent in those with delayed GE.</p><p><strong>Conclusion: </strong>The 5-year incidence of GISE among patients initiating GLP-1RA therapy was over 50%. While the ability to predict GISE was modest, female sex, baseline GI symptoms, and concomitant medications were associated with an increased risk. Among the small, symptom-selected subgroup referred for testing, only a third had delayed GE.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":"e70458"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Nausea Is Not Just Nausea: A Multi-Center, Cross-Sectional Study of Children and Young Adults.","authors":"Khalil El-Chammas, Lauren Hagenstein, Ashish Chogle, Neha Santucci, Kahleb Graham, Lev Dorfman, Daniel R Kelly, Jason E Dranove, Rachel Rosen, Samuel Nurko, Joseph Croffie, Keshawadhana Balakrishnan, Eric H Chiou, Pippa Simpson, Katja Karrento","doi":"10.1111/nmo.70447","DOIUrl":"https://doi.org/10.1111/nmo.70447","url":null,"abstract":"<p><strong>Background: </strong>Chronic nausea is commonly associated with disorders of gut-brain interaction (DGBI). Pediatric functional nausea (FN) is defined as predominant nausea generally unrelated to meals. It is unclear if FN is a distinct entity or clustered with pain-associated DGBI. This multi-center study aimed to investigate the burden and comorbidities of FN and compare it to other DGBI.</p><p><strong>Methods: </strong>Patients ages 8-21 years with DGBI were enrolled in a cross-sectional, multi-center observational registry across seven outpatient gastroenterology clinics and classified by Rome IV criteria. FN was compared to non-FN DGBI using validated symptom surveys: (1) Nausea Severity Scale (NSS), (2) Abdominal Pain Index (API), (3) PROMIS Global Health Scale (GHS), (4) PROMIS Pediatric Anxiety, (5) PROMIS Pediatric Depression, (6) Children's Somatization Inventory (CSI), and (7) Functional Disability Inventory (FDI).</p><p><strong>Key results: </strong>292 subjects were analyzed. Fifty (17%) met FN criteria, of which 72% were female. Eighty-four and 32% of FN patients also met criteria for functional dyspepsia (FD) post-prandial distress subtype and irritable bowel syndrome (IBS), respectively. FN versus non-FN reported greater abdominal pain (p = 0.008), anxiety (p = 0.007) and depression (p = 0.002). FN versus IBS more commonly had long-term nausea and abdominal pain (p = 0.011, p = 0.014), postural dizziness (p = 0.034), migraines (p < 0.001), lower global health (p = 0.003), along with greater anxiety (p < 0.001) and depression (p < 0.001).</p><p><strong>Conclusions and inferences: </strong>Children who meet formal FN criteria do not have isolated nausea. FN overlaps highly with pain-associated DGBI, and nearly all FN patients report abdominal pain. FN is coupled with extra-intestinal symptoms, mental health comorbidities, and poor global health.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":"e70447"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Food Avoidance Meets Compatible Diagnostic Criteria: Avoidant/Restrictive Food Intake Disorder Features in Irritable Bowel Syndrome.","authors":"Hiba Mikhael-Moussa, Alexandra Aupetit, Olivia Guérin, Charlotte Desprez, Francesco Monti, Julien Grosjean, Guillaume Gourcerol, Anne-Marie Leroi, Najate Achamrah, Chloé Melchior","doi":"10.1111/nmo.70456","DOIUrl":"https://doi.org/10.1111/nmo.70456","url":null,"abstract":"<p><strong>Background: </strong>Alone, the Nine Item Avoidant/Restrictive Food Intake Disorder (ARFID) Screen (NIAS) only allows for ARFID-like symptom detection, potentially overestimating its prevalence. We aimed to investigate the prevalence of ARFID-like symptoms and DSM-5-compatible ARFID (based on medical chart review) in irritable bowel syndrome (IBS), and to compare characteristics associated with these definitions.</p><p><strong>Methods: </strong>Adult patients with IBS according to Rome IV criteria, consulting in our tertiary care center between January 2024 and February 2025, were included. Patient data were collected using validated questionnaires, including NIAS-Fr. ARFID-like symptoms were defined as meeting the cut-off for at least one NIAS-Fr subscale (≥ 10 on \"picky\" or \"fear,\" or ≥ 9 on \"appetite\"). A medical chart review using our center's clinical data warehouse was conducted for detecting medical impairment and eating disorder (ED) diagnosis. Patients with a positive NIAS-Fr, without ED, and with at least one medical/psychosocial impairment were considered to be in the \"DSM-5 compatible ARFID\" group. Univariate and multiple logistic regression analyses were conducted.</p><p><strong>Key results: </strong>Among the 326 included patients, 47.5% had ARFID-like symptoms, and 33.4% met DSM-5-compatible criteria for ARFID. Functional dyspepsia (FD) was prevalent in 60.4% of patients. Depressive symptoms, somatic symptom severity, and FD were independently associated with having ARFID-like symptoms (Nagelkerke R² = 0.138). Depressive symptoms and IBS symptom severity were independently associated with DSM-5 compatible ARFID (Nagelkerke R² = 0.203).</p><p><strong>Conclusions and inferences: </strong>ARFID-like symptoms were more prevalent than DSM-5-compatible ARFID in our population. Applying DSM-5-compatible criteria was associated with more severe gastrointestinal and depressive symptoms. Standardized DSM-5 ARFID assessment methods remain to be established.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":"e70456"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global IBS, Local Patterns: Regional Variability in Pain, Bloating, and Impact on Daily Life Among Asian/Australian and European Patients From the Aegis Epidemiology Survey.","authors":"Christian von Muhlenbrock, Florencia Carbone, Cedric Van de Bruaene, Lukas Michaja Balsiger, Luis G Alcala-Gonzalez, Karin Herrera, Esther Colomier, Jan Tack, Tim Vanuytsel","doi":"10.1111/nmo.70453","DOIUrl":"10.1111/nmo.70453","url":null,"abstract":"<p><strong>Background: </strong>Irritable bowel syndrome (IBS) shows substantial geographic variability in symptom presentation, but regional differences in the clinical relevance of bloating remain poorly understood. We aimed to characterize regional differences in IBS phenotype, symptom burden, psychological and quality-of-life measures, and meal-related symptoms between Asian/Australian and European populations, with particular emphasis on the contribution of bloating to disease burden.</p><p><strong>Methods: </strong>We performed a cross-sectional analysis of the multinational AEGIS survey including adults fulfilling Rome IV criteria for IBS from 11 centers across Asia/Australia and Europe. Participants completed validated assessments of IBS subtype, symptom severity, quality of life, psychological burden, and dietary triggers. Regional comparisons used nonparametric and chi-square tests.</p><p><strong>Results: </strong>Among 1074 participants, 339 met Rome IV criteria for IBS. The proportion of IBS patients was lower in Asia/Australia than in Europe (20.9% vs. 40.9%, p = 0.039). IBS-D (57.1% vs. 35.9%, p < 0.001) predominated in Asia/Australia, whereas IBS-M (31.6% vs. 20.0%, p = 0.028) was more common in Europe. European patients demonstrated higher psychological burden and greater overall symptom severity despite comparable abdominal pain intensity. Bloating severity was significantly higher in European participants (p < 0.001) and showed a substantially stronger association with impaired quality of life than pain (r = -0.552, p < 0.001 vs. r = -0.260, p = 0.005). Postprandial symptoms were more common in Europe, whereas in Asia/Australia, they were associated with greater consumption of dairy products, gluten-containing foods, coffee, and carbonated beverages.</p><p><strong>Conclusions: </strong>IBS phenotype and symptom burden differ across regions. Bloating, rather than abdominal pain, was more strongly associated with impaired quality of life, supporting symptom-centered and culturally tailored IBS management.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":"e70453"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Classification of Human Gastric Enteric Neurons.","authors":"John B Furness","doi":"10.1111/nmo.70437","DOIUrl":"https://doi.org/10.1111/nmo.70437","url":null,"abstract":"","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":"e70437"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and Management of Actionable Primary Motor Esophagogastric Junction Outflow Obstruction: Clinical Practice Update of the European Society of Neurogastroenterology and Motility.","authors":"Pierfrancesco Visaggi, C Prakash Gyawali, Walter W Chan, Dustin A Carlson, Nicola de Bortoli, Adriana Lazarescu, John E Pandolfino, Sabine Roman, Stefano Siboni, Frank Zerbib, Edoardo Vincenzo Savarino","doi":"10.1111/nmo.70466","DOIUrl":"10.1111/nmo.70466","url":null,"abstract":"<p><strong>Background: </strong>Primary motor esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder identified by high-resolution manometry (HRM) in the absence of an underlying structural or mechanical cause of obstruction. The clinical significance, management, and prognosis of primary motor EGJOO remain uncertain. This clinical practice update provides expert guidance on the evaluation and management of EGJOO, with particular emphasis on determining when the condition is \"actionable\"-that is, likely to benefit from lower esophageal sphincter (LES)-directed therapies.</p><p><strong>Methods: </strong>With the endorsement of the European Society of Neurogastroenterology and Motility, an 11-member international Working Group developed recommendation statements on EGJOO, focusing on the diagnosis and management of actionable primary motor EGJOO. Statements were developed based on available literature evidence and presented at virtual meetings. Each statement was voted upon by the Working Group, and statements reaching ≥ 80% agreement were included as recommendations.</p><p><strong>Results: </strong>Twelve statements reached the agreement threshold. In summary, the Working Group agrees that actionable primary motor EGJOO should be defined by the coexistence of clinical symptoms, a characteristic HRM pattern, and non-manometric corroborative tests, including endoscopy, barium esophagogram, and functional lumen imaging probe panometry, in the absence of secondary causes. Patients with actionable primary motor EGJOO may receive medical, endoscopic, and/or surgical treatment, based on level of confidence in the diagnosis, while those without do not require LES-directed invasive intervention.</p><p><strong>Conclusions: </strong>This clinical practice update represents an evidence and expert opinion-based consensus on the most appropriate diagnostic and therapeutic workup of actionable primary motor EGJOO.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":"e70466"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Endoscopic Pyloric Dilation Beneficial in Gastroparesis? Available Data and Unresolved Issues.","authors":"William L Hasler","doi":"10.1111/nmo.70471","DOIUrl":"https://doi.org/10.1111/nmo.70471","url":null,"abstract":"","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 10","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}