No description available.

No description available.

No description available.

Genes, pathways & transcription factors involved in probiotic mediated resolution of gut inflammation in IL10-KO mice an animal model of Inflammatory Bowel Disease. An integrated Gene, Protein and Bioinformatics Approach The IL10-KO mouse is a model of human inflammatory bowel disease (IBD), used to study host microbial interactions and potential therapeutics. Affymetrix microarray and proteomics analysis on colon of WT and IL10-KO mice and cecum of IL10-KO and WT mice orally administered with and without probiotic VSL#3 was performed and identified signalling pathways and transcription factors relevant to gut inflammation and anti-inflammatory probiotics. Results were validated by Real-time PCR, immunocytochemistry, proteomics, histopathology and via pathway signature analysis of publicly available microarray data. Changes in metabolically active bacteria in response to VSL#3 were assessed with DGGE. Inflammation in IL10-KO mice was characterised by up-regulation of immune/inflammatory and down-regulation of lipid/xenobiotic metabolism and PPAR signalling. VSL#3 resolved inflammation in the cecum inducing down-regulation of genes in immune/inflammatory pathways, decrease in the number of CCL5 positive T cells and up-regulation of galectin2, known to trigger apoptosis of T cells. VSL#3 induced up-regulation of PPARα/PPAR signalling and lipid/xenobiotic metabolism, antagonistic to NFB signalling and reduced metabolically active bifidobacteria. Analysis of publicly available data showed results were relevant to human IBD, indicated that antigen processing/presentation is up-regulated early on during development of colitis in IL10-KO mice, identified the potential of PPARα/PPAR signalling to induce down-regulation of CCL5, CD3 & antigen processing/presentation, and the potential of the xenobiotic metabolism to induce down-regulation of cytokine-cytokine interaction & mitosis. As VSL#3 treatment of IL10-KO mice induced up-regulation of PPARα/PPAR signalling and xenobiotic metabolism these results provide a possible mechanistic explanation for the VSL#3 induced down-regulation of CCL5, CD3, antigen processing/presentation, cytokine-cytokine interaction and mitosis in the cecum of VSL#3 treated IL10-KO mice.

Les Maladies Inflammatoires Chroniques de l’Intestin (MICI) comprennent la maladie de Crohn (MC) et la rectocolite hémorragique (RCH). Ce sont des inflammations chroniques du tube digestif dont les causes sont inconnues. Une meilleure connaissance de leur épidémiologie pourrait orienter vers des pistes étiologiques. Jusqu’à la création du Registre EPIMAD en 1988, il n’existait en France aucune donnée d’incidence. Nous avons créé en 1988 une étude prospective d’incidence des MICI, reconnu «Registre» par l’Inserm et l’InVS en 1992. Le territoire couvert par Epimad comporte le Nord, le Pas-de-Calais, la Somme et la Seine-Maritime avec près de 6 millions d’habitants soit 9,3% de la population française. La collection des cas repose sur une collaboration multidisciplinaire incluant les gastroentérologues (GE) (libéraux, hospitaliers, adultes et pédiatres; n=262), les services d’Epidémiologie de Lille et Rouen, la plateforme d’aide méthodologique en Biostatistiques du CHRU de Lille et les Centres Hospitalo-Universitaires de Lille, Amiens et Rouen. Neuf enquêteurs se déplacent sur les lieux de consultation des GE et recueillent les informations nécessaires à la validation des diagnostics. Deux GE experts revoient chaque dossier indépendamment et posent le diagnostic final de MC ou RCH certaine, probable ou possible, de colite indéterminée, de colite aiguë ou de colite inclassée. Pour les cas atypiques et non classés, un suivi systématique est effectué pour le classement définitif (MICI ou non MICI). Un croisement des bases du Registre et des bases hospitalières est effectué une fois par an pour mesurer l’exhaustivité. 80% des cas incidents sont diagnostiqués par les GE libéraux, 13% par les GE des hôpitaux généraux et 7% par les GE universitaires. Entre 1988 et 2008, l’incidence moyenne des MICI était de 11,3/105 habitants (6,4 pour la MC, 4,4 pour la RCH et 0,5 pour IBDU). Pendant cette période, l’incidence de la MC a augmenté de 30% (100% chez l’adolescent) alors que celle de la RCH est restée stable. Le délai diagnostique médian était de 3 mois dans la MC et de 2 mois dans la RCH. Le pourcentage de patients ayant un diagnostic posé plus de 9 mois après l’apparition des symptômes a diminué avec le temps. La validité diagnostique dans les cas non classant d’emblée a été assurée par un suivi de 2 ans et a montré que seul l’âge < 40 ans était prédictif d’une évolution vers une MICI chez un patient présentant une colite aiguë. Nous avons aussi mis en évidence des présentations cliniques différentes en fonction de l’âge. Ainsi, chez l’adulte jeune, la MC est plus étendue que chez les sujets > 60 ans au diagnostic. Grâce à un nombre élevé de cas incidents, une hétérogénéité spatiale de l’incidence des MICI a été montrée dans les zones agricoles et suburbaines sans lien avec le niveau social des populations. En utilisant la méthode des statistiques de scan rajoutant la dimension temporelle à l’analyse spatiale, nous avons trouvé plusieurs clusters de sur et sous incidence constants dans le temps. Nos perspectives sont: 1) Poursuivre l’enregistrement des cas incidents et établir des données de prévalence; 2) Etudier les facteurs de risque environnementaux par des études d’épidémiologie analytique (corrélations écologiques, études cas témoins, études exposés-non exposés); 3) Etudier les facteurs de risque génétiques (fréquence des variants NOD2) dans la population du Registre; 4) Créer une étude prospective sur les paramètres prédictifs (profil génétique, profil métagénomique du microbiote intestinal, profil sérologique) de développer une MC dans une population de sujets à haut risque (sujets indemnes de MC âgés de 10 à 35 ans et appartenant à une famille multiplexe, à la descendance de formes conjugales ou à une paire de jumeaux discordants). Conclusions: EPIMAD est le plus gros Registre mondial sur les MICI en population générale, reconnu pour la qualité de ses travaux, rendu possible par la création d’un réseau-ville-hôpital unique. / Inflammatory Bowel Disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) are among the most serious and perplexing of digestive diseases. Their pathophysiology remains poorly understood. Geographic variations in the incidence of IBD could offer new clues about environmental risk factors. There were no data concerning the incidence of IBD in France. We created the first French prospective study on IBD incidence in 1988. This study became “Registre” recognized by Inserm and InVS in 1992. This prospective study was performed through all gastroenterologists (GE) (n=262) of the region of Nord, Pas-de-Calais, Somme and Seine-Maritime including near of 6 million of inhabitants corresponding to 9.3% of the whole French population. Collection of new cases is based on a close multidisciplinary collaboration including GE (whatever their practice), Epidemiology Unit of Hospital and University of Lille and Rouen, Biostatistics Unit of Lille Hospital and University and Academic Hospitals of Amiens, Lille and Rouen. Each GE referred patients consulting for the first time with clinical symptoms compatible with IBD. Data are collected by 9 interviewer practitioners present at the GE’s consulting room. Two independent experts GE assessed each case independently and made a final diagnosis of definite, probable, possible CD, UC or ulcerative proctitis (UP); Inflammatory Bowel Disease unclassifiable (IBDU); acute colitis or unspecified colitis. Possible cases of IBD, acute colitis and unspecified colitis are systematically followed-up and when a new event is recorded the chart is reviewed by the experts and a new final diagnosis is made. A control of the completeness collection is made each year by crossing data from Hospital Health databases. 80% of incident cases have been reported by private GE, 13% by general hospitals and 7% by academic centres. From 1988 to 2008 the mean annual incidence was 11.3/105 inhabitants for IBD including 6.4 for CD, 4.4 for UC and 0.5 for IBDU with a ratio CD/UC of 1.45. During this period CD incidence increased by 30% (100% in young adults) while that of UC remained stable. Valuable clinical information has been obtained; median time between onset of symptoms and diagnosis was 3 months in CD and 2 months in UC. The number of patients with a diagnosis delay > 9 months decreased over time. Age < 40 years at diagnosis was the only clinical predictor for subsequent IBD in patients with an initial diagnosis of acute colitis. Clinical presentation according to age at diagnosis may influence clinical course of IBD. In younger patients IBD had a more disabling course than in the elderly-onset IBD patients. Thanks to the large number of incident cases, we assessed spatial IBD incidence variation at the canton level and analyzed its association with a deprivation index. A spatial heterogeneity was found with a noteworthy predominance of CD in agricultural areas but no significant link with deprivation. We completed the spatial analysis using spatial scan statistics methods allowing revealing several time-constant (since 1988) clusters and other time-varying clusters. Perspectives: 1) To continue to record incident cases and establish prevalence data of IBD; 2) To study environmental risk factors using epidemiological analytic studies; 3) To study genetic risk factors establishing a geographic map of NOD2 variants in the EPIMAD’s area and 4) To assess the predictiveness of patient microbiota and host factors in a prospective, longitudinal study enrolling yet-healthy subjects at risk to develop CD (healthy patients aged 10-35 years and belonging to discordant twins, to offspring of IBD affected couples and to IBD multiplex families). In conclusion, since 1988, the EPIMAD registry has been recognized as a valuable tool for studies on genetic and environmental risk factors. It has also made it possible to reinforce networking between private practices, general and university hospitals at a regional level.

BACKGROUND: Inflammatory bowel disease (IBD) is a group of conditions characterized by chronic inflammation of the gastrointestinal (GI) tract. A new diagnosis of IBD in children and adolescents can have significant psychosocial effects on both the patient and the family. Child and parental coping strategies play a crucial role in the adjustment to IBD, especially within the first year of the diagnosis. AIMS: The primary aim of the study was to assess the stability of coping measures over time in children and parents following a new pediatric IBD diagnosis. The study also aimed to assess the impact of parental coping on parental healthcare resource utilization for children with newly diagnosed IBD, as well as the impact of parental coping on anxiety, depression, and quality of life in children with newly diagnosed IBD. METHODS: This was a prospective, longitudinal cohort study at Boston Children’s Hospital (BCH) that focused on children and adolescents with newly diagnosed IBD, as well as their parents. Patients and their parents were approached at the time they enrolled in the study and then again about 12 months later as part of a one-year follow-up. At both time points, they were asked to fill out various questionnaires about psychological functioning and answer other questions about medical care. RESULTS: The study identified and encountered 465 IBD patients, of which 126 were eligible for recruitment. There were 70 patients and families who signed a consent form for enrollment, 55 who fully or partially completed the questionnaires at baseline, and only 5 who also completed the questionnaires at follow-up. Due to the limited number of participants who completed the questionnaires at follow-up, no definitive conclusions could be drawn about the stability of coping measures over time. Parental anxiety, parental depression, frequent parental stress, and difficult parental stress were all found to be positively correlated with healthcare utilization and negatively correlated with the child’s quality of life. Parental anxiety, frequent parental stress, and difficult parental stress were all found to be positively correlated with the child’s anxiety. Parental depression, frequent parental stress, and difficult parental stress were all found to be positively correlated with the child’s depression. CONCLUSION: Preliminary findings suggest that poor parental coping leads to decreased child quality of life and increased healthcare utilization, child anxiety, and child depression. A larger sample size is needed to accurately evaluate the stability of coping measures over time. The next steps for this study involve further examination of the impact of parental coping and enrollment of more patients and families.

No description available.

Murine small intestinal CD103+ dendritic cells (DCs) produce retinoic acid (RA) through retinaldehyde dehydrogenase (RALDH) activity, thereby inducing ‘gut-homing’ α4β7 and CCR9 on T cells they activate, enhancing TGF-β-mediated induction of Foxp3+ regulatory T cells and suppressing induction of pro-inflammatory TH17 cells. RALDH activity of CD103+ DCs is reduced in mouse models of inflammatory bowel disease (IBD) but the role of RALDH activity in human intestinal DCs in the pathogenesis of IBD is undefined. This project aimed to determine the influence of inflammation on RALDH activity of antigen presenting cell (APC) subsets including CD103+ DCs within human distal intestinal mucosa. RALDH activity was identified by Aldefluor assay in intestinal DCs (CD103+ and CD103- subsets) alongside ALDH1A2 expression in healthy controls. In contrast with mouse models, RALDH activity was not reduced in CD103+ DCs from IBD patients. An increased frequency of CD14+ macrophages (MФ) of IBD patients displayed ALDH1A1-associated RALDH activity compared with healthy controls. Blood CD14+ monocytes, putative precursors of intestinal CD14+ MФ, of healthy controls and IBD patients displayed ALDH1A1-associated RALDH activity indicating RALDH is systemically acquired by monocytes and upregulated within the mucosa of IBD patients, or alternatively that RALDH+ monocytes are selectively recruited in IBD. In vitro, inhibition of RA receptor-α signalling blocked GM-CSF-mediated differentiation of TNFα-producing pro-inflammatory RALDH+ CD14+ MФ from monocytes, consistent with enhanced RALDH activity of intestinal CD14+ MФ in IBD supporting a pro-inflammatory phenotype. Soluble intestinal mediators including prostaglandin E2 suppressed RALDH activity of MoDCs in vitro, whilst mediators from inflamed IBD mucosa conditioned MoDCs to imprint enhanced levels of α4β7 expression on naive CD4+ T cells independent of RALDH activity. This study provides the first systematic analysis of RALDH activity in human intestinal APCs and indicates important distinctions between mouse models and human IBD.

Background and Aims Sacral nerve stimulation (SNS) is an established therapy for faecal incontinence (FI). Percutaneous tibial nerve stimulation (PTNS) is a newer, less-invasive treatment. The effectiveness, cost and acceptability of these treatments have not been systematically compared. Methods A systematic review of neuromodulation interventions for FI and an investigator-blinded, randomised pilot trial of PTNS vs. SNS including parallel quantitative (clinical outcomes and cost) and qualitative studies. Results The systematic review determined on intention-to-treat, the median success rates for SNS were 63% (range 33-66%), 58% (range 52-81%) and 54% (range 50-58%) in the short, medium and long terms respectively. The success rate for PTNS was 59% at 12 months. In the pilot trial: 40 patients (39 female; mean age 59 years) met eligibility criteria. As designed, 23 were randomised to receive SNS and 17 PTNS. 15 patients progressed to permanent SNS implantation and 16 patients received a full course of PTNS. Within group effect sizes were marginally greater for SNS than PTNS on available case analysis. FI episodes per week at baseline, 3 months and 6 months follow-up: SNS median 5.75 (IQR 5.75-15.5 ) [mean 11.4 (SD 12.0)], 2.5 (2-4.5) [4.0 (4.0)], 1.75 (1.5-5) [4.9 (6.9)], vs. PTNS median 6.5 (IQR 2.5- 16.5) [mean 10.6 (SD 11.2)], 3.5 (0.75-7.25) [5.8 (6.9)], 2.5 (0.75-10.75) [6.3 (6.9)]. At least 50% improvement in FI episodes per week at 6 months: SNS 61% vs. PTNS 47%. Effect estimates for SNS with chronic implanted stimulation were larger (67% at 6 months). Clinical FI scores and quality of life improvements complemented these results. Qualitative analysis demonstrated a very high acceptability and safety profile for both treatments. Total costs were £2,906 (SD £122) per patient for PTNS and £12,748 (SD £4,175) for SNS. Conclusions Definitive trial data between SNS or PTNS is lacking. This RCT pilot study determined that in the short-term, SNS confers a small clinical benefit over PTNS for FI but is much more expensive.

Introduktion: Irritable bowel syndrome [IBS] är den vanligaste kroniska sjukdomen som uppträder i gastrointestinal-kanalen. Sjukdomen förekommer hos 10–20% av världsbefolkningen och kan upptäckas hos både barn och vuxna. Etiologin för IBS är mycket komplex och ännu inte helt klarlagd då det saknas fullständig förståelse för den patofysiologiska processen. IBS kännetecknas ofta av buksmärtor, magkramper, uppblåsthet, förstoppning och diarré. Definitionen av coping är en konstant kognitiv och beteendemässig förändring i syfte om att kunna hantera yttre och inre påfrestningar, som överstiger personens förmåga att hantera dem. Där det finns olika copingstrategier att tillämpa för att hantera en viss situation. Syfte: Syftet med litteraturstudien var att belysa copingstrategier vid IBS.   Metod: Litteraturstudie genomfördes i enlighet med Polit och Becks (2017) nio steg. Litteraturstudiens resultat grundas på tio vetenskapliga artiklar. Resultat: Resultatet delades in i kategorier, första kategorin var Copingstrategier i sociala sammanhang där underkategorierna som identifierades var Söka stöd och information som copingstrategi och Utforska personliga copingstrategier. Den andra kategorin var Copingstrategier för att anpassa sig till det dagliga livet, där underkategorierna som identifierades var Rutiner och vanor som copingstrategi, Kosthantering som copingstrategi och Fysisk aktivitet som copingstrategi. Den sista kategorin var Psykologiska copingstrategier, där underkategorierna som identifierades var Inställning och kontroll som copingstrategi och Undvikande och anpassade copingstrategier i sociala sammanhang. Slutsats: Personer med IBS upplever att copingstrategier är nödvändiga för att kunna hantera sjukdomen. Det är därför viktigt att personen utforskar strategier som passar personen bäst, genom att prova olika strategier och se vilka som fungerar kort- och långsiktigt. En förutsättning för att kunna tillämpa copingstrategierna är att ha kunskap om vikten av individualiserade copingstrategier, samt att en kombination av flera strategier är nödvändigt för att kunna kontrollera situationen.