145 results on '"Emmanuel Mas"'
Search Results
2. Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life
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Caroline Carlé, Delphine Boucher, Luisa Morelli, Camille Larue, Ekaterina Ovtchinnikova, Louise Battut, Kawthar Boumessid, Melvin Airaud, Muriel Quaranta-Nicaise, Jean-Luc Ravanat, Gilles Dietrich, Sandrine Menard, Gérard Eberl, Nicolas Barnich, Emmanuel Mas, Marie Carriere, Ziad Al Nabhani, and Frédérick Barreau
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Perinatal period ,Foodborne TiO2 ,Intestinal barrier function ,Intestinal stem cells ,Microbiota ,Colitis ,Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background Perinatal exposure to titanium dioxide (TiO2), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO2 exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO2 until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days). Epigenetic marks was studied by DNA methylation profile measuring the level of 5-methyl-2′-deoxycytosine (5-Me-dC) in DNA from colic epithelial cells. The susceptibility to develop IBD has been monitored using dextran-sulfate sodium (DSS)-induced colitis model. Germ-free mice were used to define whether microbial transfer influence the mucosal homeostasis and subsequent exacerbation of DSS-induced colitis. Results In pregnant and lactating mice, foodborne TiO2 was able to translocate across the host barriers including gut, placenta and mammary gland to reach embryos and pups, respectively. This passage modified the chemical element composition of foetus, and spleen and liver of mothers and their offspring. We showed that perinatal exposure to TiO2 early in life alters the gut microbiota composition, increases the intestinal epithelial permeability and enhances the colonic cytokines and myosin light chain kinase expression. Moreover, perinatal exposure to TiO2 also modifies the abilities of intestinal stem cells to survive, grow and generate a functional epithelium. Maternal TiO2 exposure increases the susceptibility of offspring mice to develop severe DSS-induced colitis later in life. Finally, transfer of TiO2-induced microbiota dysbiosis to pregnant germ-free mice affects the homeostasis of the intestinal mucosal barrier early in life and confers an increased susceptibility to develop colitis in adult offspring. Conclusions Our findings indicate that foodborne TiO2 consumption during the perinatal period has negative long-lasting consequences on the development of the intestinal mucosal barrier toward higher colitis susceptibility. This demonstrates to which extent environmental factors influence the microbial-host interplay and impact the long-term mucosal homeostasis.
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- 2023
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3. Accuracy of Serological Screening for the Diagnosis of Celiac Disease in Type 1 Diabetes Children
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Chloé Girard, Aurélie De Percin, Carole Morin, Maeva Talvard, Françoise Fortenfant, Nicolas Congy-Jolivet, Claire Le Tallec, Jean-Pierre Olives, and Emmanuel Mas
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diabetes mellitus ,type 1 ,celiac disease ,HLA antigens ,antibodies ,children ,Medicine (General) ,R5-920 - Abstract
Background and Objectives: Patients with type 1 diabetes (T1D) are considered at high-risk for developing celiac disease (CD). The purpose of our study was to determine the prevalence of CD among children who were followed in our unit for T1D using the latest ESPGHAN guidelines, and avoiding intestinal biopsies in some of the children. Materials and Methods: We performed a prospective monocentric study, which included 663 T1D children between June 2014 and June 2016. We considered CD according to serological (tissue transglutaminase (TGAs) and endomysium antibodies) results. Children were included either at the time of T1D diagnosis or during their follow up. We looked for clinical and biochemical signs of CD, and for T1D characteristics. Results: The children’s ages ranged from 11 months to 18 years. CD was confirmed in 32 out of 663 patients with T1D, with a prevalence of 4.8%. CD was excluded in 619 children and remained uncertain for 12 children, who had positive TGAs without the required criteria. We found that 95% of T1D children express HLA-DQ2 and/or -DQ8, which was 2.4 times higher than in the general population. Conclusions: An intestinal biopsy could be avoided to confirm CD in the majority of T1D children. Silent forms of CD are frequent and screening is recommended for all patients. Importantly, repeated TGA assessment is required in HLA genetically predisposed T1D patients, while it is unnecessary in the 5% who are HLA-DQ2 and -DQ8 negative.
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- 2023
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4. Pediatric endoscopy training across Europe: a survey of the ESPGHAN National Societies Network 2016–2019
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Alexandra Papadopoulou, Carmen Ribes-Koninckx, Alastair Baker, Maria Noni, Eleni Koutri, Maria-Vasiliki Karagianni, Sue Protheroe, Alfredo Guarino, Emmanuel Mas, Michael Wilschanski, Enriqueta Roman, Johanna Escher, Raoul I. Furlano, Carsten Posovszky, Ilse Hoffman, Jiri Bronsky, Almuthe Christine Hauer, Duska Tjesic-Drinkovic, Maria Fotoulaki, Rok Orel, Vaidotas Urbonas, Aydan Kansu, Miglena Georgieva, and Mike Thomson
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and study aims The ability to perform endoscopy procedures safely and effectively is a key aspect of quality clinical care in Pediatric Gastroenterology, Hepatology and Nutrition (PGHN). The aim of this survey, which was part of a global survey on PGHN training in Europe, was to assess endoscopy training opportunities provided across Europe. Methods Responses to standardized questions related to endoscopy training were collected from training centers across Europe through the presidents/representatives of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition National Societies from June 2016 to December 2019. Results A total of 100 training centers from 19 countries participated in the survey. In 57 centers, the endoscopy suit was attached to the PGHN center, while in 23, pediatric endoscopies were performed in adult endoscopy facilities. Ninety percent of centers reported the availability of specialized endoscopy nurses and 96 % of pediatric anesthetists. Pediatric endoscopies were performed by PGHN specialists in 55 centers, while 31 centers reported the involvement of an adult endoscopist and 14 of a pediatric surgeon. Dividing the number of procedures performed at the training center by the number of trainees, ≤ 20 upper, lower, or therapeutic endoscopies per trainee per year were reported by 0 %, 23 %, and 56 % of centers, respectively, whereas ≤ 5 wireless capsule endoscopies per trainee per year by 75 %. Only one country (United Kingdom) required separate certification of competency in endoscopy. Conclusions Differences and deficiencies in infrastructure, staffing, and procedural volume, as well as in endoscopy competency assessment and certification, were identified among European PGHN training centers limiting training opportunities in pediatric endoscopy.
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- 2022
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5. Long-Term Outcomes in Real Life of Lumacaftor–Ivacaftor Treatment in Adolescents With Cystic Fibrosis
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Stéphanie Bui, Alexandra Masson, Raphaël Enaud, Léa Roditis, Gaël Dournes, François Galode, Cyrielle Collet, Emmanuel Mas, Jeanne Languepin, Michael Fayon, Fabien Beaufils, and Marie Mittaine
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cystic fibrosis ,child ,CFTR potentiator ,CFTR corrector ,lung function testing ,nutritional status ,Pediatrics ,RJ1-570 - Abstract
Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment.Materials and Methods: In this tri-center, non-interventional, and observational cohort study, children (12–18 years old) were assessed prospectively during the 2 years of therapy, and retrospectively during the 2 years preceding treatment. Data collected and analyzed for the study were exclusively extracted from the medical electronic system records of the patients.Results: Forty adolescents aged 12.0–17.4 years at LUM/IVA initiation were included. The lung function decreased significantly during and prior to treatment and increased after LUM/IVA initiation, becoming significant after 2 years of treatment. LUM/IVA significantly improved the BMI Z-score and sweat chloride concentration. By contrast, there was no significant change in exacerbation rates, antibiotic use, or CT scan scores. Age at LUM/IVA initiation was lower in good responders and associated with greater ppFEV1 change during the 2 years of treatment. LUM/IVA was well-tolerated.Conclusion: In F508del homozygote adolescents, real-life long-term LUM/IVA improved the ppFEV1 trajectory, particularly in the youngest patients, nutritional status, and sweat chloride concentration but not exacerbation rates or radiological scores. LUM/IVA was generally well-tolerated and safe.
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- 2021
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6. Cytolethal Distending Toxin Promotes Replicative Stress Leading to Genetic Instability Transmitted to Daughter Cells
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William Tremblay, Florence Mompart, Elisa Lopez, Muriel Quaranta, Valérie Bergoglio, Saleha Hashim, Delphine Bonnet, Laurent Alric, Emmanuel Mas, Didier Trouche, Julien Vignard, Audrey Ferrand, Gladys Mirey, and Anne Fernandez-Vidal
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cytolethal distending toxin ,replicative stress ,genetic instability ,DNA bridge ,DNA damage ,human colorectal organoid ,Biology (General) ,QH301-705.5 - Abstract
The cytolethal distending toxin (CDT) is produced by several Gram-negative pathogenic bacteria. In addition to inflammation, experimental evidences are in favor of a protumoral role of CDT-harboring bacteria such as Escherichia coli, Campylobacter jejuni, or Helicobacter hepaticus. CDT may contribute to cell transformation in vitro and carcinogenesis in mice models, through the genotoxic action of CdtB catalytic subunit. Here, we investigate the mechanism of action by which CDT leads to genetic instability in human cell lines and colorectal organoids from healthy patients’ biopsies. We demonstrate that CDT holotoxin induces a replicative stress dependent on CdtB. The slowing down of DNA replication occurs mainly in late S phase, resulting in the expression of fragile sites and important chromosomic aberrations. These DNA abnormalities induced after CDT treatment are responsible for anaphase bridge formation in mitosis and interphase DNA bridge between daughter cells in G1 phase. Moreover, CDT-genotoxic potential preferentially affects human cycling cells compared to quiescent cells. Finally, the toxin induces nuclear distension associated to DNA damage in proliferating cells of human colorectal organoids, resulting in decreased growth. Our findings thus identify CDT as a bacterial virulence factor targeting proliferating cells, such as human colorectal progenitors or stem cells, inducing replicative stress and genetic instability transmitted to daughter cells that may therefore contribute to carcinogenesis. As some CDT-carrying bacterial strains were detected in patients with colorectal cancer, targeting these bacteria could be a promising therapeutic strategy.
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- 2021
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7. NOD2 Expression in Intestinal Epithelial Cells Protects Toward the Development of Inflammation and Associated CarcinogenesisSummary
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Audrey Ferrand, Ziad Al Nabhani, Núria Solà Tapias, Emmanuel Mas, Jean-Pierre Hugot, and Frédérick Barreau
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan-conserved motifs in cytosol and stimulates host immune response including epithelial and immune cells. The association of NOD2 mutations with a number of inflammatory pathologies including Crohn’s disease (CD), graft-versus-host diseases, or Blau syndrome, highlights its pivotal role in inflammatory response and the associated-carcinogenesis development. Since its identification in 2001 and its association with CD, the role of NOD2 in epithelial cells and immune cells has been investigated extensively but the precise mechanism by which NOD2 mutations lead to CD and the associated carcinogenesis development is largely unknown. In this review, we present and discuss recent developments about the role of NOD2 inside epithelial cells on the control of the inflammatory process and its linked carcinogenesis development. Keywords: Nod2, Cancer, Colitis, Gut, Epithelial cells
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- 2019
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8. Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients
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Emilie d’Aldebert, Muriel Quaranta, Morgane Sébert, Delphine Bonnet, Sylvain Kirzin, Guillaume Portier, Jean-Pierre Duffas, Sophie Chabot, Philippe Lluel, Sophie Allart, Audrey Ferrand, Laurent Alric, Claire Racaud-Sultan, Emmanuel Mas, Céline Deraison, and Nathalie Vergnolle
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inflammation ,Crohn’s disease ,ulcerative colitis ,organoid ,intestine ,Biology (General) ,QH301-705.5 - Abstract
Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders, where epithelial defects drive, at least in part, some of the pathology. We reconstituted human intestinal epithelial organ, by using three-dimension culture of human colon organoids. Our aim was to characterize morphological and functional phenotypes of control (non-IBD) organoids, compared to inflamed organoids from IBD patients. The results generated describe the epithelial defects associated with IBD in primary organoid cultures, and evaluate the use of this model for pharmacological testing of anti-inflammatory approaches. Human colonic tissues were obtained from either surgical resections or biopsies, all harvested in non-inflammatory zones. Crypts were isolated from controls (non-IBD) and IBD patients and were cultured up to 12-days. Morphological (size, budding formation, polarization, luminal content), cell composition (proliferation, differentiation, immaturity markers expression), and functional (chemokine and tight junction protein expression) parameters were measured by immunohistochemistry, RT-qPCR or western-blot. The effects of inflammatory cocktail or anti-inflammatory treatments were studied in controls and IBD organoid cultures respectively. Organoid cultures from controls or IBD patients had the same cell composition after 10 to 12-days of culture, but IBD organoid cultures showed an inflammatory phenotype with decreased size and budding capacity, increased cell death, luminal debris, and inverted polarization. Tight junction proteins were also significantly decreased in IBD organoid cultures. Inflammatory cytokine cocktail reproduced this inflammatory phenotype in non-IBD organoids. Clinically used treatments (5-ASA, glucocorticoids, anti-TNF) reduced some, but not all parameters. Inflammatory phenotype is associated with IBD epithelium, and can be studied in organoid cultures. This model constitutes a reliable human pre-clinical model to investigate new strategies targeting epithelial repair.
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- 2020
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9. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, Prognostic and Therapeutic Tools?
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Vickie Lacroix, Alexis Cassard, Emmanuel Mas, and Frederick Barreau
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inflammatory bowel disease ,Crohn’s disease ,ulcerative colitis ,microbiota ,omics ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Inflammatory bowel diseases (IBDs), which include Crohn’s disease and ulcerative colitis, are multifactorial diseases that involve in particular a modification of the gut microbiota, known as dysbiosis. The initial sets of metataxonomic and metagenomic data first made it possible to approximate the microbiota profile in IBD. In addition, today the new ‘omics’ techniques have enabled us to draw up a functional and integrative map of the microbiota. The key concern in IBD is to develop biomarkers that allow us to assess the activity of the disease and predict the complications and progression, while also guiding the therapeutic care so as to develop personalized medicine. In this review, we present all of the latest discoveries on the microbiota provided by “omics” and we outline the benefits of these techniques in developing new diagnostic, prognostic and therapeutic tools.
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- 2021
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10. Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer
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Morgane Sébert, Nuria Sola-Tapias, Emmanuel Mas, Frédérick Barreau, and Audrey Ferrand
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protease-activated receptors (PARs) ,small intestine ,colon ,gut ,inflammation ,cancer ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Protease-activated receptors (PARs) belong to the G protein-coupled receptor (GPCR) family. Compared to other GPCRs, the specificity of the four PARs is the lack of physiologically soluble ligands able to induce their activation. Indeed, PARs are physiologically activated after proteolytic cleavage of their N-terminal domain by proteases. The resulting N-terminal end becomes a tethered activation ligand that interact with the extracellular loop 2 domain and thus induce PAR signal. PARs expression is ubiquitous and these receptors have been largely described in chronic inflammatory diseases and cancer. In this review, after describing their discovery, structure, mechanisms of activation, we then focus on the roles of PARs in the intestine and the two main diseases affecting the organ, namely inflammatory bowel diseases and cancer.
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- 2019
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11. How Can a Polymeric Formula Induce Remission in Crohn’s Disease Patients?
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Kawthar Boumessid, Frederick Barreau, and Emmanuel Mas
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Crohn’s disease ,inflammatory bowel disease ,exclusive enteral nutrition ,mucosal healing ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Crohn’s disease is an inflammatory bowel disease whose prevalence is increasing worldwide. Among medical strategies, dietary therapy with exclusive enteral nutrition is recommended as a first-line option, at least for children, because it induces clinical remission and mucosal healing. Modulen®, a polymeric TGF-β2 enriched formula, has good palatability and is widely used. For the first time in the literature, this review outlines and discusses the clinical outcomes obtained with this therapy, as well as the potential mechanisms of action of its compounds. It can be explained by its TGF-β2 content, but also by its protein and lipid composition. Further well-designed studies are required to improve our knowledge and to optimize therapeutic strategies.
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- 2021
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12. Increased Fecal Calprotectin Is Associated with Worse Gastrointestinal Symptoms and Quality of Life Scores in Children with Cystic Fibrosis
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Fabien Beaufils, Emmanuel Mas, Marie Mittaine, Martin Addra, Michael Fayon, Laurence Delhaes, Haude Clouzeau, François Galode, Thierry Lamireau, Stéphanie Bui, and Raphaël Enaud
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intestinal inflammation ,reflux ,nausea ,gas ,pancreatic insufficiency ,Medicine - Abstract
In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children’s stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQLTM and the Quality of Life Pediatric Inventory 4.0-PedsQLTM. Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 µg/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, “Heart Burn Reflux”, “Nausea and Vomiting”, and “Gas and Bloating”). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores.
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- 2020
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13. Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis harra through GSK3β regulation in intestinal cells
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Imen Nasri, Rachid Chawech, Cynthia Girardi, Emmanuel Mas, Audrey Ferrand, Nathalie Vergnolle, Nicolas Fabre, Raoudha Mezghani-Jarraya, and Claire Racaud-Sultan
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flavonoids ,intestine ,inflammation ,cancer ,glycogen synthase kinase 3β ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Context and objective: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 β (GSK3β) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3β and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3β. Materials and methods: Methanol extracts from D. harra flowers were prepared and the bio-guided fractionation of their active compounds was performed using inflammatory [protease-activated receptor 2 (PAR2)-stimulated IEC6 cells] and cancer (human Caco-2 cell line) intestinal cells. 50–100 μg/mL of fractions or compounds purified by HPLC were incubated with cells whose inhibited form of GSK3β (Pser9 GSK3β) and survival were analyzed by Western blot at 1 h and colorimetric assay at 24 h, respectively. LC-UV-MS profiles and MS-MS spectra were used for the characterization of extracts and flavonoids-enriched fractions, and the identification of pure flavonoids was achieved by MS and NMR analysis. Results: The methanol extract from D. harra flowers and its flavonoid-enriched fraction inhibit GSK3β in PAR2-stimulated IEC6 cells. GSK3β inhibition by the flavonoid-enriched D. harra fraction was dependent on PKC activation. The flavonoid-enriched D. harra fraction and its purified compound isorhamnetin-3,7-di-O-glucoside induced a 20% decrease of PAR2-stimulated IEC6 and Caco-2 cell survival. Importantly, normal cells (non-stimulated IEC6 cells) were spared by these treatments. Conclusion: This work indicates that flavonoids from D. harra display cytotoxic activity against inflammatory and cancer intestinal cells which could depend on GSK3β inhibition.
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- 2017
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14. French Recommendations for Sugar Intake in Adults: A Novel Approach Chosen by ANSES
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Luc Tappy, Béatrice Morio, Dalila Azzout-Marniche, Martine Champ, Mariette Gerber, Sabine Houdart, Emmanuel Mas, Salwa Rizkalla, Gérard Slama, François Mariotti, and Irène Margaritis
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dietary guidelines ,cardiovascular diseases ,obesity ,type 2 diabetes ,non-alcoholic fatty liver disease ,non-communicable diseases ,Nutrition. Foods and food supply ,TX341-641 - Abstract
This article presents a systematic review of the scientific evidence linking sugar consumption and health in the adult population performed by a group of experts, mandated by the French Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement, et du travail (ANSES). A literature search was performed by crossing search terms for overweight/obesity, diabetes/insulin resistance, dyslipidemia/cardiovascular diseases, non-alcoholic fatty liver diseases (NAFLD), and uric acid concentrations on one hand and for intake of sugars on the other. Controlled mechanistic studies, prospective cohort studies, and randomized clinical trials were extracted and assessed. A literature analysis supported links between sugar intake and both total energy intake and body weight gain, and between sugar intake and blood triglycerides independently of total energy intake. The effects of sugar on blood triglycerides were shown to be mediated by the fructose component of sucrose and were observed with an intake of fructose >50 g/day. In addition, prospective cohort studies showed associations between sugar intake and the risk of diabetes/insulin resistance, cardiovascular diseases, NAFLD, and hyperuricemia. Based on these observations, ANSES proposed to set a maximum limit to the intake of total sugars containing fructose (sucrose, glucose–fructose syrups, honey or other syrups, and natural concentrates, etc.) of 100 g/day.
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- 2018
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15. Predictive Factors of Lamivudine Treatment Success in a Hepatitis B Virus-Infected Pediatric Cohort: A 10-Year Study
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Yasmine Yousef, Kathie Béland, Emmanuel Mas, Pascal Lapierre, Dorothée Bouron Dal Soglio, and Fernando Alvarez
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
BACKGROUND: Hepatitis B virus (HBV) infections are responsible for the development of chronic hepatitis in 400 million people worldwide. Currently, no consensus exists as to when treatment should be initiated for pediatric patients.
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- 2012
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16. IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis.
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Emmanuel Mas, Marie Danjoux, Virginie Garcia, Stéphane Carpentier, Bruno Ségui, and Thierry Levade
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Medicine ,Science - Abstract
BACKGROUND:The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH. MATERIALS AND METHODS:Steatohepatitis was induced by feeding wild-type or IL-6(-/-) mice for 5 weeks with a methionine and choline-deficient (MCD) diet. RESULTS:Whereas MCD diet-induced weight loss and decreases in serum glucose, cholesterol and triglyceride levels were similar in both genotypes, serum alanine aminotransferase was less elevated in IL-6(-/-) mice than in wild-type animals. Despite having a comparable liver steatosis score, IL-6-deficient mice exhibited less lobular inflammation than their wild-type littermates. Liver gene expression of TGF-beta and MCP-1 was also strongly attenuated in mutant mice; a more modest reduction was observed for PPAR-gamma and F4/80 transcripts as well as proteins. Chromatographic analysis of liver lipids demonstrated that MCD diet induced in normal and mutant mice a similar decrease in the ratio of phosphatidylcholine to phosphatidylethanolamine. However, the diet-induced increase in the levels of sphingomyelin and ceramide was less important in IL-6(-/-) mice. CONCLUSION:Altogether, these results indicate that IL-6 deficiency does not block the development of NASH; yet, IL-6 plays a critical role in the accompanying liver inflammation.
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- 2009
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17. Impact of the HAS 2019 French guidelines on the frequency of hospital undernutrition in children
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Margaux Richou, Olivier L. Mantha, Noël Peretti, Béatrice Dubern, Emmanuel Mas, Régis Hankard, and Arnaud De Luca
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Hospitalization ,Nutrition Assessment ,Nutritional Support ,Malnutrition ,Pediatrics, Perinatology and Child Health ,Humans ,Nutritional Status ,Child ,Hospitals - Abstract
In 2019, the French National Authority for Health (Haute Autorité de Santé, HAS) published guidelines on the diagnosis of undernutrition. The present article focuses on the impact of switching from the 2012 guidelines of the Nutrition Committee of the French Paediatric Society (CNSFP) to the HAS guidelines on the frequency of hospital undernutrition in children. We selected for the period 2010-2019 from the ePINUT database: (1) all children aged more than 2 years with (2) clinically confirmed nutritional status in (3) French sites. The frequency of undernutrition was 15.4% vs. 28.8% using the CNSFP and HAS criteria, respectively (p 0.01; n = 6304). When compared to non-malnourished children regardless of the criteria used, malnourished children: (1) stayed longer in hospital (CNSFP: 9.0 ± 11.8 vs. 6.5 ± 8.7 days, p 0.01; HAS: 7.8 ± 10.1 vs. 6.4 ± 8.4 days, p 0.01), (2) gained more weight during hospitalization (% of weight at admission) (CNSFP: +1.4 ± 4.1 vs. -0.3 ± 3.5%, p 0.01; HAS: +2.3 ± 4.7 vs. -0.1 ± 3.4%, p 0.01), and (3) received nutritional support more frequently during hospitalization (CNSFP: 20% vs. 5%, p 0.01; HAS: 13% vs. 4%, p 0.01). Switching to the HAS guidelines resulted in an almost twofold higher frequency of undernutrition in hospitalized children. Initiation of nutritional care remained low considering the nutritional status. The present study warrants interventional studies to determine which children may benefit more from nutritional therapy to improve their outcome.
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- 2023
18. Drugs in focus: Domperidone
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Maria Giovanna Puoti, Amit Assa, Marc Benninga, Ilse Julia Broekaert, Francisco Javier Martin Carpi, Marco Deganello Saccomani, Jernej Dolinsek, Matjaz Homan, Emmanuel Mas, Erasmo Miele, Christos Tzivinikos, Mike Thompson, and Osvaldo Borrelli
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Pediatrics, Perinatology and Child Health ,Gastroenterology - Published
- 2023
19. Helicobacter pylori-negative Chronic Gastritis in Children
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Amit Assa, Osvaldo Borrelli, Ilse Broekaert, Marco Deganello Saccomani, Jernej Dolinsek, Javier Martin-de-Carpi, Emmanuel Mas, Erasmo Miele, Sara Sila, Mike Thomson, Christos Tzivinikos, Marc A. Benninga, Pediatric surgery, Paediatric Gastroenterology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Assa, Amit, Borrelli, Osvaldo, Broekaert, Ilse, Saccomani, Marco Deganello, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Sila, Sara, Thomson, Mike, Tzivinikos, Christo, and Benninga, Marc A
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Adult ,Cross-Sectional Studies ,Helicobacter pylori ,Gastritis ,Pediatrics, Perinatology and Child Health ,Eosinophilia ,Gastroenterology ,Humans ,Child ,Enteritis ,Helicobacter Infections - Abstract
OBJECTIVES: To systematically review the current evidence on Helicobacter pylori-negative chronic gastritis including natural history, available therapies and outcomes. METHODS: Articles providing data on the prevalence, treatment or outcomes of Helicobacter pylori-negative gastritis were identified through a systematic search in the MEDLINE and EMBASE databases. All original research articles from human studies until October 31, 2021, were included. RESULTS: A total of 54 studies were included consisted of eosinophilic gastritis (n = 9), autoimmune gastritis (n = 11), collagenous gastritis (n = 16), focally enhanced gastritis (n = 6), lymphocytic gastritis (n = 5) and other causes including idiopathic gastritis and chronic renal failure related (n = 7). Most of the included studies were either cross-sectional or longitudinal cohorts except for collagenous gastritis, which mainly included case reports and case series. The prevalence of paediatric eosinophilic gastritis ranges between 5 and 7/100,000 and patients have generally favourable outcome with 50% to 70% clinical and histological response to either corticosteroids or elimination diets. Autoimmune gastritis and collagenous gastritis are extremely rare entities, commonly present with refractory iron deficiency anaemia, while lymphocytic gastritis is relatively common (10%-45%) in children with coeliac disease. Data on treatments and outcomes of autoimmune, collagenous, and focally enhanced gastritis are lacking with limited data implying poor response to therapy in the former 2 diagnoses. CONCLUSIONS: Helicobacter pylori-negative gastritis is uncommonly reported, mainly in small cohorts, mixed adult-paediatric cohorts or as sporadic case reports. As common symptoms are not specific, thus not always result in an endoscopic evaluation, the true prevalence of these distinct disorders may be underestimated, and thus under reported.
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- 2022
20. Training in Paediatric Clinical Nutrition Across Europe
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Alexandra Papadopoulou, Carmen Ribes-Koninckx, Alastair Baker, Maria Noni, Eleni Koutri, Maria-Vasiliki Karagianni, Sue Protheroe, Alfredo Guarino, Emmanuel Mas, Michael Wilschanski, Enriqueta Roman, Johanna Escher, Raoul I. Furlano, Carsten Posovszky, Ilse Hoffman, Gabor Veres, Jiri Bronsky, Almuthe Christine Hauer, Duska Tjesic-Drinkovic, Maria Fotoulaki, Rok Orel, Vaidotas Urbonas, Aydan Kansu, Miglena Georgieva, Berthold Koletzko, Papadopoulou, Alexandra, Ribes-Koninckx, Carmen, Baker, Alastair, Noni, Maria, Koutri, Eleni, Karagianni, Maria-Vasiliki, Protheroe, Sue, Guarino, Alfredo, Mas, Emmanuel, Wilschanski, Michael, Roman, Enriqueta, Escher, Johanna, Furlano, Raoul I, Posovszky, Carsten, Hoffman, Ilse, Veres, Gabor, Bronsky, Jiri, Hauer, Almuthe Christine, Tjesic-Drinkovic, Duska, Fotoulaki, Maria, Orel, Rok, Urbonas, Vaidota, Kansu, Aydan, Georgieva, Miglena, Koletzko, Berthold, and Pediatrics
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Europe ,children ,clinical nutrition training ,training in paediatric gastroenterology ,hepatology and nutrition ,Surveys and Questionnaires ,Pediatrics, Perinatology and Child Health ,Gastroenterology ,Humans ,Child ,Child Nutritional Physiological Phenomena ,Societies, Medical - Abstract
OBJECTIVES/BACKGROUND: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres. METHODS: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019. RESULTS: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) and home parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of
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- 2022
21. [Infant gastroesophageal reflux disease: physiological or pathological ?]
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Aurélie, Bourchany and Emmanuel, Mas
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Gastroesophageal Reflux ,Humans ,Proton Pump Inhibitors ,Milk Hypersensitivity ,Esophagitis, Peptic - Abstract
PHYSIOLOGICAL OR PATHOLOGICAL ? Gastroesophageal reflux (GER) is defined by the rise of gastric contents into the esophagus, with or without externalization. GER is very common in young infants, with a peak around 4 months, and most often physiological due to high milk intakes and inappropriate relaxation of the lower esophageal sphincter. Evoking a GER disease (GERD) is not always obvious due to signs of poor specificity (crying, irritability, regurgitation). On the other hand, one should not miss warning signs evocative of GERD complicated by esophagitis or of recurrent upper respiratory or ENT infections, or even differential diagnoses (cow milk protein allergy, eosinophilic esophagitis, congenital malformations or brain tumours, etc.). The diagnosis of GERD is clinical but investigations can sometimes be discussed like esophagogastroduodenal endoscopy, 24- hour pH-metry, esophagogastroduodenal follow through. The mechanisms of GERD should be clearly explained to parents and physiological GER should be treated with non-drug measures (adaptation of milk intakes/volumes, thickeners). In the absence of improvement, avoidance of cow's milk proteins for 2 to 4 weeks can be proposed, or even treatment with proton pump inhibitors.PHYSIOLOGIQUE OU PATHOLOGIQUE ? Le reflux gastro-oesophagien (RGO) est défini par la remontée du contenu gastrique dans l’oesophage, avec ou sans extériorisation. Le RGO est très fréquent chez le nourrisson, avec un pic vers 4 mois. Il est le plus souvent physiologique, en raison d’une alimentation lactée importante et d’une relaxation inappropriée du sphincter inférieur de l’oesophage. Évoquer un RGO pathologique n’est pas toujours évident, car ses symptômes ont une mauvaise spécificité (pleurs, irritabilité, régurgitations). En revanche, il ne faut pas passer à côté de signes d’alarme évocateurs d’un RGO compliqué par une oesophagite ou par des infections respiratoires hautes ou ORL récidivantes, ni négliger les diagnostics différentiels (allergie aux protéines du lait de vache, oesophagite à éosinophiles, malformations congénitales ou tumeurs cérébrales...). Le diagnostic de RGO est clinique, mais certains examens complémentaires peuvent parfois être discutés : endoscopie oesogastroduodénale, pH-métrie des 24 heures, transit oesogastroduodénal. Il convient de bien expliquer aux parents les mécanismes du RGO et de prendre en charge sa forme physiologique par des mesures non médicamenteuses (adaptation des prises/volumes de lait, épaississants). En l’absence d’amélioration, une éviction des protéines du lait de vache peut être proposée pendant deux à quatre semaines, voire un traitement par inhibiteurs de la pompe à protons.
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- 2022
22. Systematic review and meta‐analysis: the incidence and prevalence of paediatric coeliac disease across Europe
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Osvaldo Borrelli, Christos Tzivinikos, Corina Pienar, Carmen Ribes-Koninckx, John Williams, Kym Thorne, Ilse Broekaert, Stephen E. Roberts, Javier Martín-de-Carpi, Ann John, Emmanuel Mas, Nikhil Thapar, Marc A. Benninga, Rut Anne Thomassen, Mike Thomson, Jernej Dolinsek, Sian Morrison-Rees, Erasmo Miele, Roberts, Stephen E, Morrison-Rees, Sian, Thapar, Nikhil, Benninga, Marc A, Borrelli, Osvaldo, Broekaert, Ilse, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Ribes-Koninckx, Carmen, Thomassen, Rut A, Thomson, Mike, Tzivinikos, Christo, Thorne, Kymberley, John, Ann, Williams, John G, Swansea University, Great Ormond Street Hospital for Children [London] (GOSH), University College of London [London] (UCL), Children’s Health Queensland [Brisbane] (CHQ), University of Amsterdam [Amsterdam] (UvA), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], University of Sheffield [Sheffield], Al Jalila Children's Specialty Hospital, and European Society for Paediatric Gastroenterology Hepatology and Nutrition
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Pediatrics ,medicine.medical_specialty ,MEDLINE ,Age at diagnosis ,Cochrane Library ,Asymptomatic ,Coeliac disease ,Serology ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Prevalence ,medicine ,Humans ,Pharmacology (medical) ,Child ,Aged ,Autoantibodies ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Hepatology ,business.industry ,Incidence ,Incidence (epidemiology) ,Gastroenterology ,Infant ,medicine.disease ,3. Good health ,Europe ,Celiac Disease ,Child, Preschool ,Meta-analysis ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background: Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. Aim: To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. Methods: Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. Results: The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages
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- 2021
23. Cell Centred Finite Element Model for Intestinal Organoids Shape Analysis: From tissue architecture to mechanics
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julien laussu, deborah michel, stephane segonds, steven marguet, frederick barreau, dimitri hamel, emmanuel mas, audrey ferrand, and florian bugarin
- Abstract
Organoids, established from stem cells owing to their self-renewal and differentiation capacities, are self-organised three-dimensional tissue culture recapitulating the original cell populations and their associated functions, as well as tissue architecture. The intestinal organoids established from adult stem cells isolated from the intestinal crypts, recreate 3D epithelial mini-intestines. They represent an excellent tool to study intestinal stem cell capacities and their ability to reconstitute a fully polarised and functional epithelium. These 3D cultures recapitulate \textit{in vitro} the tissue characteristics, including architecture, either in physiological or disease conditions whether they are established from healthy or pathological tissue samples respectively. In this regard, their use for potential treatments screening carries the hopes for a future personalized medicine for which image-analysis such as HCS are increasingly being developed. Numerous numerical models have been developed to study the effects of organoid development on their shape. Most of them remain mainly restricted in their physical description due to the complex inter-relationship between cell physics, phenotypes and behaviors, exploding the number of variables in modeling formulation. Finite Element Method (FEM) is a numerical analysis method employed in mechanics to model deformation and evaluate residual stress of complex structures making it difficult to obtain analytical solutions. Considering epithelial architecture as a homogeneous material where each cell is an elemental equivalent part of the problem, FEM allows a direct link between tissue architecture deformations and local mechanical constraints. Here we formalise a new organoid cell centred FEM with a physical description borrowed from the engineering world. This model can allow a better understanding of the individual contribution of physical/mechanical properties of individual cells on general tissue architecture.
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- 2022
24. Diagnostic de la dénutrition de l’enfant : recommandation de bonne pratique HAS-FFN 2019
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Jacques Delarue, Francisca Joly, Emmanuel Mas, Eric Fontaine, Béatrice Dubern, Marie-Paule Vasson, Alexandre Pitard, and Jean-Claude Desport
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0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,Nutrition and Dietetics ,030309 nutrition & dietetics ,030212 general & internal medicine - Abstract
La denutrition chez l’enfant se traduit par un retard de croissance et une perte de poids involontaire. Elle compromet le developpement psychomoteur du jeune enfant. Elle majore le risque d’infection et augmente le risque de complications medicales et chirurgicales. L’objectif de cette recommandation de bonne pratique est de definir la denutrition chez l’enfant (< 18 ans) et de proposer des criteres afin d’ameliorer son diagnostic a l’aide d’outils adaptes.
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- 2020
25. Optimization of biologics to reduce treatment failure in inflammatory bowel diseases
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Anne Breton, Frédérick Barreau, Emmanuel Mas, Cyrielle Gilletta De Saint-Joseph, Aurélie Bourchany, Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, Département de Gastroentérologie, Hôpital Rangueil, CHU de Toulouse, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CCSD, Accord Elsevier, Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Gastroentérologie et pancréatologie [CHU Toulouse], and Pôle Maladies de l'appareil digestif [CHU Toulouse]
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0301 basic medicine ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Drug Resistance ,Drug resistance ,Antibodies, Monoclonal, Humanized ,030226 pharmacology & pharmacy ,Inflammatory bowel disease ,law.invention ,Efficacy ,03 medical and health sciences ,0302 clinical medicine ,Gastrointestinal Agents ,Randomized controlled trial ,law ,Drug Discovery ,medicine ,Humans ,Treatment Failure ,Intensive care medicine ,media_common ,Pharmacology ,Biological Products ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,Inflammatory Bowel Diseases ,medicine.disease ,3. Good health ,030104 developmental biology ,Therapeutic drug monitoring ,Monoclonal ,Trough level ,Ustekinumab ,Drug Monitoring ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Moderate to severe inflammatory bowel disease patients can fail to respond to conventional therapy and/or to biologic treatment. In the era of TNFα antagonists and other non-anti-TNF biologic drugs, it is important to review the literature on biologic treatment failure, which could be defined as primary non-response, secondary loss of response and intolerance. Therapeutic drug monitoring (TDM), that is, drug trough level and antidrug antibodies, should enable to determine the mechanisms of treatment failure and to optimize drug efficacy. There is a consensus on reactive TDM at the time of loss of response. Proactive TDM could be of interest during induction and/or maintenance, but randomized controlled trials are required.
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- 2020
26. Safety of Thiopurine Use in Paediatric Gastrointestinal Disease
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Jernej Dolinsek, Christos Tzivinikos, Rut Ann Thomassen, Erasmo Miele, Carmen Ribes-Koninckx, Nikhil Thapar, Rok Orel, Corina Pienar, Ilse Broekaert, Mike Thomson, Emmanuel Mas, Marc A. Benninga, 'Federico II' University of Naples Medical School, University of Amsterdam [Amsterdam] (UvA), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], NHS Foundation Trust [London], The Royal Marsden, Al Jalila Children's Specialty Hospital, University College of London [London] (UCL), Queensland Paediatric Infectious Diseases Laboratory [Australia], University of Queensland [Brisbane]-Children's Health Research Centre, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Miele, E., Benninga, M. A., Broekaert, I., Dolinsek, J., Mas, E., Orel, R., Pienar, C., Ribes-Koninckx, C., Thomassen, R. A., Thomson, M., Tzivinikos, C., and Thapar, N.
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Infliximab therapy ,medicine.medical_specialty ,Autoimmune hepatitis ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Gastrointestinal Agents ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,Recurrence ,inflammatory bowel disease ,030225 pediatrics ,Steroid sparing ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,Immunologic Factors ,6-mercaptopurine ,Adverse effect ,Intensive care medicine ,Child ,azathioprine ,Thiopurine methyltransferase ,biology ,autoimmune hepatitis ,Crohn disease ,business.industry ,Mercaptopurine ,thiopurines ,Gastroenterology ,medicine.disease ,Inflammatory Bowel Diseases ,3. Good health ,Gastrointestinal disease ,Pediatrics, Perinatology and Child Health ,biology.protein ,adverse effects ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn disease recurrence where there is moderate risk of this occurring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. The routine clinical use of thiopurines has, however, been questioned due to a number of potential adverse effects. The aim of this article is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.
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- 2020
27. Diagnostic de la dénutrition de l’adulte de moins de 70 ans : recommandation de bonne pratique HAS-FFN 2019
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Emmanuel Mas, Francisca Joly, Jean-Claude Desport, Marie-Paule Vasson, Béatrice Dubern, Jacques Delarue, Eric Fontaine, Alexandre Pitard, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Federation Francaise de Nutrition (FFN), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Toulouse [Toulouse]
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0303 health sciences ,03 medical and health sciences ,Dénutrition ,0302 clinical medicine ,Nutrition and Dietetics ,030309 nutrition & dietetics ,[SDV]Life Sciences [q-bio] ,030209 endocrinology & metabolism ,Adulte ,Aide au diagnostic médical - Abstract
International audience; La dénutrition est un problème majeur de santé publique qui concerne plus de 2 millions de personnes en France. Elle se traduit par une perte de poids involontaire. Elle majore le risque d’infection et réduit la force musculaire et la mobilité. Elle augmente le risque de complications médicales et chirurgicales. L’objectif de cette recommandation de bonne pratique est de définir la dénutrition chez l’adulte (
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- 2020
28. Régime végétalien chez l’enfant et l’adolescent. Recommandations du Groupe francophone d’hépatologie, gastroentérologie et nutrition pédiatriques (GFHGNP)
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gastroentérologie et nutrition pédiatriques Groupe francophone d’hépatologie, J. Lemale, Marc Bellaiche, Emmanuel Mas, Patrick Tounian, and C. Jung
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0301 basic medicine ,03 medical and health sciences ,030109 nutrition & dietetics ,0302 clinical medicine ,030225 pediatrics ,General Medicine - Abstract
Resume L’engouement actuel pour les regimes vegetaliens n’epargne pas la population pediatrique. Ce type de regime, n’assurant pas tous les besoins en micronutriments, expose les enfants a des carences nutritionnelles. Celles-ci peuvent avoir des consequences graves, particulierement lorsque ce regime est mis en place des le plus jeune âge, periode de croissance importante et de developpement neurologique. Meme si les carences ont moins de retentissement chez l’enfant plus âge et l’adolescent, elles ne sont pas rares et doivent donc aussi etre prevenues. Un suivi dietetique regulier est indispensable, une supplementation en vitamine B12 et vitamine D est toujours necessaire, alors que le fer, le calcium, l’acide docosahexaenoique et le zinc doivent faire l’objet d’une supplementation au cas par cas.
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- 2020
29. New European Recommendations for the Diagnosis of Celiac Disease in Children: Did the Experts Make it Simple?
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Jean-Pierre, Olives, primary, Salma, Burayzat, additional, and Emmanuel, Mas, additional
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- 2016
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30. Diagnosing undernutrition children and adults: new French criteria. Why, for what and for whom? A joint statement of the French National Authority for Health and French Federation of Nutrition - Corrigendum
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Jacques, Delarue, Jean-Claude, Desport, Béatrice, Dubern, Francisca, Joly, Emmanuel, Mas, Alexandre, Pitard, and Eric, Fontaine
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- 2021
31. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, Prognostic and Therapeutic Tools?
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Frédérick Barreau, Emmanuel Mas, Alexis Cassard, Vickie Lacroix, CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Toulouse [Toulouse], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DGOS (Reference Center of Rare Digestive Diseases of Toulouse University Hospital), the patient association François Aupetit, Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and SEGUIN, Nathalie
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Crohn’s disease ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Review ,Disease ,Gut flora ,Bioinformatics ,Inflammatory bowel disease ,0302 clinical medicine ,A ,E ,Precision Medicine ,Biology (General) ,Phylogeny ,Spectroscopy ,0303 health sciences ,Crohn's disease ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,biology ,Microbiota ,General Medicine ,Ulcerative colitis ,3. Good health ,Computer Science Applications ,Chemistry ,Mas ,Disease Progression ,030211 gastroenterology & hepatology ,F. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic ,QH301-705.5 ,Omics ,digestive system ,eulcerative colitis ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Barreau ,030304 developmental biology ,Bacteria ,business.industry ,V ,Organic Chemistry ,Cassard ,Lacroix ,Inflammatory Bowel Diseases ,medicine.disease ,biology.organism_classification ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,digestive system diseases ,Prognostic inflammatory bowel disease ,[SDV.BIO] Life Sciences [q-bio]/Biotechnology ,Gastrointestinal Microbiome ,Crohn's diseas ,Metagenomics ,Personalized medicine ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,business ,Dysbiosis ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Inflammatory bowel diseases (IBDs), which include Crohn’s disease and ulcerative colitis, are multifactorial diseases that involve in particular a modification of the gut microbiota, known as dysbiosis. The initial sets of metataxonomic and metagenomic data first made it possible to approximate the microbiota profile in IBD. In addition, today the new ‘omics’ techniques have enabled us to draw up a functional and integrative map of the microbiota. The key concern in IBD is to develop biomarkers that allow us to assess the activity of the disease and predict the complications and progression, while also guiding the therapeutic care so as to develop personalized medicine. In this review, we present all of the latest discoveries on the microbiota provided by “omics” and we outline the benefits of these techniques in developing new diagnostic, prognostic and therapeutic tools.
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- 2021
32. Drugs in Focus: Octreotide Use in Children With Gastrointestinal Disorders
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Osvaldo Borrelli, Erasmo Miele, C Ribes Koninckx, Rut Ann Thomassen, J Martin de-Carpi, Marc A. Benninga, Ilse Broekaert, Jernej Dolinsek, Christo Tzivinikos, Corina Pienar, Emmanuel Mas, Mike Thomson, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Great Ormond Street Hospital for Children [London] (GOSH), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), University of Amsterdam [Amsterdam] (UvA), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, and VU University Medical Center [Amsterdam]
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medicine.medical_specialty ,Gastrointestinal bleeding ,Gastrointestinal Diseases ,Octreotide ,Lymphangiectasia ,somatostatin ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Gastrointestinal Agents ,children ,Chylous ascites ,Internal medicine ,chylous ascites ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,Child ,business.industry ,Chylothorax ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,medicine.disease ,bleeding ,3. Good health ,Clinical trial ,diarrhoea ,Pancreatitis ,Pharmaceutical Preparations ,ocreotide ,030220 oncology & carcinogenesis ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Acute Disease ,Pediatrics, Perinatology and Child Health ,Acute pancreatitis ,030211 gastroenterology & hepatology ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,medicine.drug - Abstract
International audience; Octreotide, a somatostatin analogue, has been used for more than 20 years in children with gastrointestinal bleeding, chylothorax or chylous ascites, intestinal lymphangiectasia, pancreatitis, intestinal dysmotility, and severe diarrhoea; however, until now, there is a lack of randomised clinical trials evaluating the efficacy of this compound in childhood. Hence, we aimed to review the literature in order to determine the evidence of its use and safety in children, using PubMed from 2000 to 2021 with the search terms "octreotide" and "children" and "bleeding or chylous ascites or chylothorax or acute pancreatitis or lymphangiectasia or diarrhoea or intestinal dysmotility".
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- 2021
33. Scanner thoracique chez l’enfant atteint de mucoviscidose : intérêt d’un protocole en expiration séquentielle pour réduire la dose d’irradiation
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Emmanuel Mas, M. Michelet, C. Baunin, J. Vial, S. Simon, L. Roditis, and M. Mittaine
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Pulmonary and Respiratory Medicine ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,medicine.diagnostic_test ,business.industry ,medicine ,Computed tomography ,030212 general & internal medicine ,Nuclear medicine ,business - Abstract
Resume Introduction Le scanner thoracique est essentiel pour le suivi respiratoire des enfants atteints de mucoviscidose, mais sa repetition expose a la toxicite potentielle des radiations ionisantes. L’objectif de cette etude etait de comparer un protocole scanographique complet (acquisition en inspiration helicoidale puis expiration sequentielle) a un protocole ne comprenant que les coupes expirees, en termes d’analyse d’image et de dose delivree de radiations ionisantes. Methodes Sur une cohorte monocentrique de 57 enfants âges de 5 a 18 ans, 78 examens ont ete scores par deux radio-pediatres sur le protocole complet puis uniquement sur les coupes expirees. Resultats La correlation entre les scores radiologiques globaux obtenus selon les deux protocoles etait tres bonne (r = 0,90 pour les deux radiologues) ainsi que pour les scores de bronchectasies (r = 0,72 et 0,86), impactions mucoides (r = 0,87 et 0,83) et trappage expiratoire (r = 0,96 et 0,92). Les parametres d’irradiation etaient reduits, avec un produit dose longueur (DLP) passant de 103,31 mGy.cm (protocole complet) a 3,06 mGy.cm (protocole expiration seule) (p Conclusion Afin d’espacer la realisation de scanners complets plus irradiants, l’utilisation d’un protocole avec seulement des coupes expirees permettrait un diagnostic tomodensitometrique de qualite tout en reduisant l’irradiation chez les enfants atteints de mucoviscidose.
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- 2020
34. An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology
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Rut Ann Thomassen, Jernej Dolinsek, Carmen Ribes-Koninckx, Erasmo Miele, Christos Tzivinikos, Corina Pienar, Javier Martín-de-Carpi, Emmanuel Mas, Marc A. Benninga, Osvaldo Borrelli, Ilse Broekaert, Mike Thomson, University Hospital of Cologne [Cologne], Great Ormond Street Hospital for Children [London] (GOSH), University medical centre Maribor (UKC Maribor), Hospital Sant Joan de Déu [Barcelona], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oslo University Hospital [Oslo], Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, VU University Medical Center [Amsterdam], SEGUIN, Nathalie, Broekaert, Ilse Julia, Borrelli, Osvaldo, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Ribes-Koninckx, Carmen, Thomassen, Rut, Thomson, Mike, Tzivinikos, Christo, Benninga, Marc, and Hospital Universitari i Politècnic La Fe
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medicine.medical_specialty ,Malabsorption ,Consensus ,Carbohydrate malabsorption ,030309 nutrition & dietetics ,MEDLINE ,carbohydrate malabsorption ,small intestinal bacterial overgrowth ,Helicobacter pylori infection ,Helicobacter Infections ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,children ,Internal medicine ,Small intestinal bacterial overgrowth ,medicine ,breath testing ,Humans ,Intensive care medicine ,Exocrine pancreatic insufficiency ,Child ,Children ,0303 health sciences ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,Gastroenterology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Hepatology ,medicine.disease ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,3. Good health ,Fat malabsorption ,Breath testing ,Systematic review ,Breath Tests ,Pediatrics, Perinatology and Child Health ,Position paper ,030211 gastroenterology & hepatology ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Systematic Reviews as Topic - Abstract
International audience; Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.
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- 2021
35. MTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion
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Henry Taylor, Marta C. Cohen, Stephan Buderus, Charis Eng, Isabel Rojas, Kevin Sweet, Peter Dale, Natalia Nedelkopoulou, Victor L. Fox, Claudia Phen, Inés Loverdos, Holm H. Uhlig, Tim G. J. de Meij, Jürgen Heise, Isabel Spier, Dilay Yerlioglu, Stefan Aretz, Emmanuel Mas, Veronica Busoni, Mike Thomson, Antje Ballauff, Imperial College London, Istanbul University, University of Texas Southwestern Medical Center [Dallas], Helios Klinikum Krefeld - Helios Klinikum Krefeld, Sheffield Children's NHS Foundation Trust, University Hospital Bonn, University of Barcelona, Italian Hospital of Buenos Aires, Helios Klinikum [Erfurt], Royal Gwent Hospital, Vrije Universiteit Amsterdam [Amsterdam] (VU), Ohio State University [Columbus] (OSU), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Case Western Reserve University [Cleveland], Cleveland Clinic, Gemeinnützige Gesellschaft der Franziskanerinnen zu Olpe mbH (GFO), University of Oxford [Oxford], NIHR Oxford Biomedical Research Centre, Pediatric surgery, Amsterdam Gastroenterology Endocrinology Metabolism, and Amsterdam Reproduction & Development (AR&D)
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AcademicSubjects/SCI01140 ,03 medical and health sciences ,0302 clinical medicine ,Neoplastic Syndromes, Hereditary ,Genetics ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,PTEN ,Humans ,Enteropathy ,Juvenile polyposis syndrome ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Molecular Biology ,Genetics (clinical) ,PI3K/AKT/mTOR pathway ,Bone Morphogenetic Protein Receptors, Type I ,Colectomy ,030304 developmental biology ,0303 health sciences ,Everolimus ,biology ,Intestinal Polyposis ,TOR Serine-Threonine Kinases ,PTEN Phosphohydrolase ,General Medicine ,MTOR Inhibitors ,medicine.disease ,BMPR1A ,3. Good health ,030220 oncology & carcinogenesis ,Sirolimus ,biology.protein ,Cancer research ,General Article ,Haploinsufficiency ,Gastrointestinal Hemorrhage ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,medicine.drug - Abstract
Ultra-rare genetic disorders can provide proof of concept for efficacy of targeted therapeutics and reveal pathogenic mechanisms relevant to more common conditions. Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A). Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate. No effective pharmacological therapy exists. A multi-center cohort analysis was performed to characterize phenotype and investigate the therapeutic effect of mammalian target of rapamycin (mTOR) inhibition (adverse events, disease progression, time to colectomy and mortality) in patients with JPI. Among 25 JPI patients identified (mean age of onset 13 months), seven received mTOR inhibitors (everolimus, n = 2; or sirolimus, n = 5). Treatment with an mTOR inhibitor reduced the risk of colectomy (hazard ratio = 0.27, 95% confidence interval = 0.07–0.954, P = 0.042) and resulted in significant improvements in the serum albumin level (mean increase = 16.3 g/l, P = 0.0003) and hemoglobin (mean increase = 2.68 g/dl, P = 0.0077). Long-term mTOR inhibitor treatment was well tolerated over an accumulated follow-up time of 29.8 patient years. No serious adverse events were reported. Early therapy with mTOR inhibitors offers effective, pathway-specific and personalized treatment for patients with JPI. Inhibition of the phosphoinositol-3-kinase–AKT–mTOR pathway mitigates the detrimental synergistic effects of combined PTEN–BMPR1A deletion. This is the first effective pharmacological treatment identified for a hamartomatous polyposis syndrome., Graphical Abstract Graphical Abstract
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- 2021
36. Diagnosis, Management, and Prevention of Button Battery Ingestion in Childhood: A European Society for Paediatric Gastroenterology Hepatology and Nutrition Position Paper
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Matjaž Homan, Nikhil Thapar, Mike Thomson, Christos Tzivinikos, Lissy de Ridder, Amani Mubarak, Emmanuel Mas, Marc A. Benninga, Ilse Broekaert, Corina Pienar, Jernej Dolinsek, Erasmo Miele, University Medical Center [Utrecht], Emma Children’s Hospital, University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Great Ormond Street Hospital for Children [London] (GOSH), Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, Eramus MC-Sophia Children’s Hospital, Partenaires INRAE, Nestle SA, Danone Nutricia, Mubarak, Amani, Benninga, Marc A, Broekaert, Ilse, Dolinsek, Jernej, Homan, Matjaž, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Thapar, Nikhil, Thomson, Mike, Tzivinikos, Christo, de Ridder, Lissy, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, SEGUIN, Nathalie, and Pediatrics
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medicine.medical_specialty ,MEDLINE ,[SPI.MAT] Engineering Sciences [physics]/Materials ,Asymptomatic ,[SPI.MAT]Engineering Sciences [physics]/Materials ,Eating ,03 medical and health sciences ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Electric Power Supplies ,Esophagus ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,endoscopy ,Child ,Intensive care medicine ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,medicine.diagnostic_test ,Impaction ,business.industry ,Gastroenterology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Guideline ,Hepatology ,Foreign Bodies ,foreign body ,esophageal perforation ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,3. Good health ,Endoscopy ,caustic ingestion ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,medicine.anatomical_structure ,pediatric ,Pediatrics, Perinatology and Child Health ,Position paper ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
International audience; Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably 12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (
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- 2021
37. Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation
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Karine Duroure, Estelle Colin, Thomas Edouard, Ludovic Martin, Linda Grimaud, Lyndon Gallacher, George McGillivray, Guy Lenaers, Valérie Desquiret-Dumas, Clarisse Billon, Anne Breton, Mohammed Zarhrate, Emmanuel Mas, Dominique Bonneau, Lynn Pais, Daniel Henrion, Thomas Haaf, Reza Maroofian, Marianna Parlato, Frank M. Ruemmele, Anne-Laure Guihot, Anaïs Philippe, Ehsan Ghayoor Karimiani, Pauline E. Schneeberger, Stanislas Lyonnet, Bernadette Bègue, Bruno Moulin, Rémi Duclaux-Loras, Nicolas Cagnard, Michael Frank, Laurence Faivre, Ruben Attali, Yves Alembik, Filippo Del Bene, Kerstin Kutsche, Céline Revenu, Fabienne Charbit-Henrion, Katta M. Girisha, Aboulfazl Rad, Eyal Reinstein, Shalini S. Nayak, Barbara Vona, Nadine Cerf-Bensussan, Caroline Lekszas, Shay Tzur, Alban Ziegler, Susan M. White, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ingénierie Radioprotection Sûreté Démantèlement (IRSD), Centre National de la Recherche Scientifique (CNRS), Geroscience and rejuvenation research center (RESTORE), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Embryology and genetics of human malformation, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de Hautepierre [Strasbourg], Nouvel Hôpital Civil de Strasbourg, Tel Aviv University (TAU), Emedgene Technologies [Tel Aviv], Murdoch Children's Research Institute (MCRI), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Kasturba Medical College, Manipal, Massachusetts Institute of Technology (MIT), University College of London [London] (UCL), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, St George's, University of London, University of Würzburg = Universität Würzburg, Fondation Princesse Grace, Fondation Maladies Rares, Harbig Family Foundation, Royal Children's Hospital Foundation, University of Tubingen (2545-1-0), Federal Ministry of Education and Research (01DQ17003 to K.K.), Indian Council of Medical Research (file no. 5/7/1508/2016 to K.M.G), National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute grant UM1 HG008900, National Human Genome Research Institute grant R01 HG009141, Victorian Government's Operational Infrastructure Support Program, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-IAHU-0001,FOReSIGHT,Enabling Vision Restoration(2018), European Project: 661527,H2020,H2020-MSCA-IF-2014,NMJALS(2015), European Project: 339407,EC:FP7:ERC,ERC-2013-ADG,IMMUNOBIOTA(2014), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Embryology and genetics of human malformation (Equipe Inserm U1163), SEGUIN, Nathalie, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Enabling Vision Restoration - - FOReSIGHT2018 - ANR-18-IAHU-0001 - IAHU - VALID, In vivo analysis of neuromuscular junction stability in zebrafish models of amyotrophic lateral sclerosis - NMJALS - - H20202015-11-16 - 2017-11-15 - 661527 - VALID, Host-microbiota interactions across the gut immune system:lessons from early onset inflammatory bowel diseases and from gnotobiotic mice - IMMUNOBIOTA - - EC:FP7:ERC2014-03-01 - 2019-02-28 - 339407 - VALID, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Male ,Connective Tissue Disorder ,Loss of Heterozygosity ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,medicine.disease_cause ,IPO8 ,TGF-β signaling ,Pathogenesis ,0302 clinical medicine ,Loss of Function Mutation ,Transforming Growth Factor beta ,connective tissue disorder ,Child ,Connective Tissue Diseases ,Zebrafish ,Genetics (clinical) ,Karyopherin ,chemistry.chemical_classification ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Immunity, Cellular ,0303 health sciences ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Middle Aged ,beta Karyopherins ,Pedigree ,arterial dilatation ,Cell biology ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Phenotype ,medicine.anatomical_structure ,Cardiovascular Diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Female ,Bone Diseases ,Signal Transduction ,Adult ,Adolescent ,Connective tissue ,Biology ,Importin 8 ,Young Adult ,03 medical and health sciences ,[SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Report ,Genetics ,medicine ,Animals ,Humans ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Infant ,Immune dysregulation ,Loeys-Dietz syndrome ,biology.organism_classification ,joint hyperlaxity ,chemistry ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Transforming growth factor - Abstract
International audience; Dysregulated transforming growth factor TGF-beta signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-beta-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-beta signaling, ipo8(-/-) zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8(-/-) zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-beta signaling during development and reinforces the existing link between TGF-beta signaling and connective tissue defects.
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- 2021
38. Vegan diet in children and adolescents. Recommendations from the French-speaking Pediatric Hepatology, Gastroenterology and Nutrition Group (GFHGNP)
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J. Lemale, Patrick Tounian, Emmanuel Mas, Marc Bellaiche, and Camille Jung
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Diet, Vegan ,medicine.medical_specialty ,Pediatrics ,Adolescent ,03 medical and health sciences ,0302 clinical medicine ,Dietary monitoring ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,Vitamin B12 ,Child ,business.industry ,Malnutrition ,Vegan Diet ,Hepatology ,Micronutrient ,medicine.disease ,Docosahexaenoic acid ,Dietary Supplements ,Pediatrics, Perinatology and Child Health ,France ,business ,Pediatric population - Abstract
The current craze for vegan diets has an effect on the pediatric population. This type of diet, which does not provide all the micronutrient requirements, exposes children to nutritional deficiencies. These can have serious consequences, especially when this diet is introduced at an early age, a period of significant growth and neurological development. Even if deficiencies have less impact on older children and adolescents, they are not uncommon and consequently should also be prevented. Regular dietary monitoring is essential, vitamin B12 and vitamin D supplementation is always necessary, while iron, calcium, docosahexaenoic acid, and zinc should be supplemented on a case-by-case basis.
- Published
- 2019
39. Diagnosing undernutrition children and adults: new French criteria. Why, for what and for whom? A joint statement of the French National Authority for Health and French Federation of Nutrition
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Emmanuel Mas, Béatrice Dubern, Jean-Claude Desport, Jacques Delarue, Francisca Joly, Alexandre Pitard, Eric Fontaine, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)
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Adult ,Pediatrics ,medicine.medical_specialty ,030309 nutrition & dietetics ,Population ,Medicine (miscellaneous) ,Nutritional Status ,Guidelines as Topic ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Weight loss ,Weight Loss ,medicine ,Humans ,030212 general & internal medicine ,Obesity ,education ,Child ,Body mass index ,2. Zero hunger ,0303 health sciences ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Malnutrition ,Undernutrition ,medicine.disease ,Nutritional assessment ,3. Good health ,Systematic review ,Etiology ,medicine.symptom ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Muscle function assessment - Abstract
The objective was to establish new diagnostic criteria for undernutrition for the French population, concordant for children aged
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- 2021
40. Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation
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Perrine Rousset, Laurent Alric, Anissa Edir, Chrystelle Bonnart, Jean-Paul Motta, Céline Deraison, David Sagnat, Elena F. Verdu, Derek M. McKay, Corinne Rolland, Emmanuel Mas, Laura Guiraud, Delphine Bonnet, Nathalie Vergnolle, Muriel Quaranta-Nicaise, Etienne Buscail, Ana Carolina Rodrigues Florence, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], McMaster University [Hamilton, Ontario], University of Calgary, ANR JCJC-11JSV1 001 01, AOL-MICILIP project, ANR-12-BSV1-0030,ELAPROB-IBD,Mecanismes d'action des probiotiques recombinants pour l'Elafine: Leur utilisation possible pour traiter les maladies inflammatoires chroniques de l'intestin?(2012), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), European Project: 627487,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IOF,EPIMACASE(2014), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), SEGUIN, Nathalie, BLANC - Mecanismes d'action des probiotiques recombinants pour l'Elafine: Leur utilisation possible pour traiter les maladies inflammatoires chroniques de l'intestin? - - ELAPROB-IBD2012 - ANR-12-BSV1-0030 - BLANC - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, THE ROLE OF ELASTASE/ELASTASE INHIBITOR IN DIALOG BETWEEN INTESTINAL EPITHELIAL CELLS AND MACROPHAGES IN INFLAMMATORY BOWEL DISEASES CONTEXT - EPIMACASE - - EC:FP7:PEOPLE2014-08-06 - 2016-08-05 - 627487 - VALID, and Physiology of the Intestine: Proteases from the Epithelium - PIPE - - EC:FP7:ERC2013-04-01 - 2018-03-31 - 310973 - VALID
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0301 basic medicine ,Adult ,Male ,Proteases ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Colon ,medicine.medical_treatment ,Immunology ,Inflammation ,Disease ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Inflammatory bowel disease ,Article ,Tight Junctions ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Immunology and Allergy ,Medicine ,Humans ,Intestinal Mucosa ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Immunity, Mucosal ,Barrier function ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,Elastase ,Middle Aged ,medicine.disease ,Inflammatory Bowel Diseases ,Pathophysiology ,digestive system diseases ,3. Good health ,Up-Regulation ,030104 developmental biology ,Cytokine ,Cytokines ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,Inflammation Mediators ,business ,Leukocyte Elastase ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Imbalance between proteases and their inhibitors plays a crucial role in the development of Inflammatory Bowel Diseases (IBD). Increased elastolytic activity is observed in the colon of patients suffering from IBD. Here, we aimed at identifying the players involved in elastolytic hyperactivity associated with IBD and their contribution to the disease. We revealed that epithelial cells are a major source of elastolytic activity in healthy human colonic tissues and this activity is greatly increased in IBD patients, both in diseased and distant sites of inflammation. This study identified a previously unrevealed production of elastase 2A (ELA2A) by colonic epithelial cells, which was enhanced in IBD patients. We demonstrated that ELA2A hyperactivity is sufficient to lead to a leaky epithelial barrier. Epithelial ELA2A hyperactivity also modified the cytokine gene expression profile with an increase of pro-inflammatory cytokine transcripts, while reducing the expression of pro-resolving and repair factor genes. ELA2A thus appears as a novel actor produced by intestinal epithelial cells, which can drive inflammation and loss of barrier function, two essentials pathophysiological hallmarks of IBD. Targeting ELA2A hyperactivity should thus be considered as a potential target for IBD treatment.
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- 2021
41. Sa1535: EXCLUSIVE ENTERAL NUTRITION ENRICHED WITH TGF-β RESTORES INTESTINAL HOMEOSTASIS IN A MOUSE MODEL OF CROHN'S DISEASE
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Kawthar Boumessid, Emmanuel Mas, and Frédérick Barreau
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Hepatology ,Gastroenterology - Published
- 2022
42. Colitis Linked to Endoplasmic Reticulum Stress Induces Trypsin Activity Affecting Epithelial Functions
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Delphine Bonnet, Nathalie Vergnolle, Sylvain Kirzin, Corinne Rolland, Muriel Quaranta-Nicaise, Alexandre Denadai-Souza, Anissa Edir, Laurent Alric, Nuria Sola Tapias, Emmanuel Mas, Gilles Dietrich, Marlène Marcellin, Frédérick Barreau, Carla Cirillo, Céline Deraison, Claire Rolland-Fourcade, Odile Burlet-Schiltz, Chrystelle Bonnart, Catherine Blanpied, Guillaume Portier, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), CHU Toulouse [Toulouse], University of Calgary, ANR-11-JSV1-0001,IBD-ase,Identification des protéases impliquées dans les maladies inflammatoires chroniques de l'intestin et analyse moléculaire des conséquences de leur hyperactivité(2011), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
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0301 basic medicine ,Chemokine ,Thapsigargin ,Cell Culture Techniques ,Inflammation ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Inflammatory bowel disease ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,trypsin-like proteases ,0302 clinical medicine ,Crohn Disease ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,Trypsin ,Interleukin 8 ,sendoplasmic reticulum stress ,Barrier function ,biology ,business.industry ,Endoplasmic reticulum ,Gastroenterology ,intestinal epithelial cell ,General Medicine ,Endoplasmic Reticulum Stress ,3. Good health ,Cell biology ,Organoids ,Enterocytes ,030104 developmental biology ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Intestinal Absorption ,chemistry ,Unfolded protein response ,biology.protein ,Colitis, Ulcerative ,030211 gastroenterology & hepatology ,medicine.symptom ,permeability ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,medicine.drug - Abstract
Background and Aims Intestinal epithelial cells [IECs] from inflammatory bowel disease [IBD] patients exhibit an excessive induction of endoplasmic reticulum stress [ER stress] linked to altered intestinal barrier function and inflammation. Colonic tissues and the luminal content of IBD patients are also characterized by increased serine protease activity. The possible link between ER stress and serine protease activity in colitis-associated epithelial dysfunctions is unknown. We aimed to study the association between ER stress and serine protease activity in enterocytes and its impact on intestinal functions Methods The impact of ER stress induced by Thapsigargin on serine protease secretion was studied using either human intestinal cell lines or organoids. Moreover, treating human intestinal cells with protease-activated receptor antagonists allowed us to investigate ER stress-resulting molecular mechanisms that induce proteolytic activity and alter intestinal epithelial cell biology. Results Colonic biopsies from IBD patients exhibited increased epithelial trypsin-like activity associated with elevated ER stress. Induction of ER stress in human intestinal epithelial cells displayed enhanced apical trypsin-like activity. ER stress-induced increased trypsin activity destabilized intestinal barrier function by increasing permeability and by controlling inflammatory mediators such as C-X-C chemokine ligand 8 [CXCL8]. The deleterious impact of ER stress-associated trypsin activity was specifically dependent on the activation of protease-activated receptors 2 and 4. Conclusions Excessive ER stress in IECs caused an increased release of trypsin activity that, in turn, altered intestinal barrier function, promoting the development of inflammatory process.
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- 2021
43. Gastrointestinal Perspective of Coronavirus Disease 2019 in Children-An Updated Review
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Christos Tzivinikos, Javier Martín de Carpi, Emmanuel Mas, Jernej Dolinsek, Mike Thomson, Marco Deganello Saccomani, Ilse Broekaert, Erasmo Miele, Amit Assa, Osvaldo Borrelli, Marc A. Benninga, Assa, Amit, Benninga, Marc A, Borrelli, Osvaldo, Broekaert, Ilse, de Carpi, Javier Martin, Saccomani, Marco Deganello, Dolinsek, Jernej, Mas, Emmanuel, Miele, Erasmo, Thomson, Mike, Tzivinikos, Christos, Ben-Gurion University of the Negev (BGU), University of Amsterdam [Amsterdam] (UvA), Great Ormond Street Hospital for Children [London] (GOSH), University Hospital of Cologne [Cologne], University of Barcelona, University of Verona (UNIVR), University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, Università degli studi di Verona = University of Verona (UNIVR), and SEGUIN, Nathalie
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Diarrhea ,Abdominal pain ,paediatric ,Gastrointestinal Diseases ,medicine.medical_treatment ,coronavirus ,Peritonitis ,Review Article ,Liver transplantation ,Inflammatory bowel disease ,gastrointestinal manifestations ,03 medical and health sciences ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,0302 clinical medicine ,Immune system ,030225 pediatrics ,Medicine ,Humans ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,SARS-CoV-2 ,Gastroenterology ,COVID-19 ,medicine.disease ,Systemic Inflammatory Response Syndrome ,3. Good health ,Systemic inflammatory response syndrome ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Pediatrics, Perinatology and Child Health ,Immunology ,multisystem inflammatory disease ,Pancreatitis ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Gastrointestinal symptoms are common findings in children with severe acute respiratory syndrome coronavirus 2 infection, including vomiting, diarrhoea, abdominal pain, and difficulty in feeding, although these symptoms tend to be mild. The hepato-biliary system and the pancreas may also be involved, usually with a mild elevation of transaminases and, rarely, pancreatitis. In contrast, a late hyper-inflammatory phenomenon, termed multisystem inflammatory syndrome (MIS-C), is characterized by more frequent gastrointestinal manifestations with greater severity, sometimes presenting as peritonitis. Gastrointestinal and hepato-biliary manifestations are probably related to a loss in enterocyte absorption capability and microscopic mucosal damage caused by a viral infection of intestinal epithelial cells, hepatocytes and other cells through the angiotensin conversion enzyme 2 receptor resulting in immune cells activation with subsequent release of inflammatory cytokines. Specific conditions such as inflammatory bowel disease (IBD) and liver transplantation may pose a risk for the more severe presentation of coronavirus disease 2019 (COVID-19) but as adult data accumulate, paediatric data is still limited. The aim of this review is to summarize the current evidence about the effect of COVID-19 on the gastrointestinal system in children, with emphasis on the emerging MIS-C and specific considerations such as patients with IBD and liver transplant recipients.
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- 2021
44. Drugs in Focus: The Use of Racecadotril in Paediatric Gastrointestinal Disease
- Author
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Emmanuel Mas, Ilse Broekaert, Erasmo Miele, Christos Tzivinikos, Jernej Dolinsek, Carmen Ribes-Koninckx, Marc A. Benninga, Corina Pienar, Rut Anne Thomassen, Nikhil Thapar, Rok Orel, Mike Thomson, Victor Babeş University of Medicine and Pharmacy (UMFT), Emma Children’s Hospital Academic Medical Centre, University Hospital of Cologne, University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli studi di Napoli Federico II, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Hospital Universitario y Politécnico La Fe, Oslo University Hospital [Oslo], NHS Foundation Trust, Al Jalila Children's Specialty Hospital, UCL Great Ormond Street Institute of Child Health [London, UK], Great Ormond Street Hospital, Partenaires INRAE, Queensland Children's Hospital, Pienar, Corina, Benninga, Marc A, Broekaert, Ilse J, Dolinsek, Jernej, Mas, Emmanuel, Miele, Erasmo, Orel, Rok, Ribes-Koninckx, Carmen, Thomassen, Rut-Anne, Thomson, Mike, Tzivinikos, Christo, Thapar, Nikhil, Paediatric Gastroenterology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, Amsterdam Reproduction & Development (AR&D), ProdInra, Migration, University of Naples Federico II = Università degli studi di Napoli Federico II, and Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
- Subjects
Diarrhea ,Drug ,Thiorphan ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Gastrointestinal Diseases ,medicine.drug_class ,media_common.quotation_subject ,medicine.medical_treatment ,Pharmacology ,Racecadotril ,03 medical and health sciences ,0302 clinical medicine ,adjuvant ,030225 pediatrics ,Antidiarrhoeal ,medicine ,Humans ,Antidiarrheals ,Child ,Adverse effect ,Neprilysin ,media_common ,racecadotril ,business.industry ,digestive, oral, and skin physiology ,Gastroenterology ,medicine.disease ,Small intestine ,[SDV.BIO] Life Sciences [q-bio]/Biotechnology ,3. Good health ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,medicine.anatomical_structure ,Pharmaceutical Preparations ,Gastrointestinal disease ,Pediatrics, Perinatology and Child Health ,030211 gastroenterology & hepatology ,business ,gastroenteritis ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Adjuvant ,medicine.drug - Abstract
International audience; Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant anti-diarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant anti-diarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.
- Published
- 2020
45. Using wavelet transform and hybrid CNN – LSTM models on VOC & ultrasound IoT sensor data for non-visual maize disease detection
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Theofrida Julius Maginga, Emmanuel Masabo, Pierre Bakunzibake, Kwang Soo Kim, and Jimmy Nsenga
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CNN ,LSTM ,Wavelet ,VOC ,Ultrasound ,Maize ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Early detection of plant diseases is crucial for safeguarding crop yield, especially in regions vulnerable to food insecurity, such as Sub-Saharan Africa. One of the significant contributors to maize crop yield loss is the Northern Leaf Blight (NLB), which traditionally takes 14–21 days to visually manifest on maize. This study introduces a novel approach for detecting NLB as early as 4–5 days using Internet of Things (IoT) sensors, which can identify the disease before any visual symptoms appear. Utilizing Convolutional Neural Networks (CNN) and Long Short Term Memory (LSTM) models, nonvisual measurements of Total Volatile Organic Compounds (VOCs) and ultrasound emissions from maize plants were captured and analyzed. A controlled experiment was conducted on four maize varieties, and the data obtained were used to develop and validate a hybrid CNN-LSTM model for VOC classification and an LSTM model for ultrasound anomaly detection. The hybrid CNN-LSTM model, enhanced with wavelet data preprocessing, achieved an F1 score of 0.96 and an Area under the ROC Curve (AUC) of 1.00. In contrast, the LSTM model exhibited an impressive 99.98% accuracy in identifying anomalies in ultrasound emissions. Our findings underscore the potential of IoT sensors in early disease detection, paving the way for innovative disease prevention strategies in agriculture. Future work will focus on optimizing the models for IoT device deployment, incorporating chatbot technology, and more sensor data will be incorporated for improved accuracy and evaluation of the models in a field environment.
- Published
- 2024
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46. Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate
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Alexiane PRADELLE, Sabine MAINBOURG, Steeve PROVENCHER, Emmanuel MASSY, Guillaume GRENET, and Jean-Christophe LEGA
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Covid-19 ,Off-label treatment ,Safety ,Repurposing ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: During the first wave of COVID-19, hydroxychloroquine (HCQ) was used off-label despite the absence of evidence documenting its clinical benefits. Since then, a meta-analysis of randomised trials showed that HCQ use was associated with an 11% increase in the mortality rate. We aimed to estimate the number of HCQ-related deaths worldwide. Methods and findings: We estimated the worldwide in-hospital mortality attributable to HCQ use by combining the mortality rate, HCQ exposure, number of hospitalised patients, and the increased relative risk of death with HCQ. The mortality rate in hospitalised patients for each country was calculated using pooled prevalence estimated by a meta-analysis of published cohorts. The HCQ exposure was estimated using median and extreme estimates from the same systematic review. The number of hospitalised patients during the first wave was extracted from dedicated databases. The systematic review included 44 cohort studies (Belgium: k = 1, France: k = 2, Italy: k = 12, Spain: k = 6, Turkey: k = 3, USA: k = 20). HCQ prescription rates varied greatly from one country to another (range 16–84%). Overall, using median estimates of HCQ use in each country, we estimated that 16,990 HCQ-related in-hospital deaths (range 6267–19256) occurred in the countries with available data. The median number of HCQ-related deaths in Belgium, Turkey, France, Italy, Spain, and the USA was 240 (range not estimable), 95 (range 92–128), 199 (range not estimable), 1822 (range 1170–2063), 1895 (range 1475–2094) and 12739 (3244− 15570), respectively. Conclusions: Although our estimates are limited by their imprecision, these findings illustrate the hazard of drug repurposing with low-level evidence.
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- 2024
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47. Screening of esophageal varices in children using esophageal capsule endoscopy: a multicenter prospective study
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Cécile Talbotec, Marc Bellaiche, Jacques Cardey, Catherine Le Gall, Laure Bridoux-Henno, Thierry Lamireau, Jérôme Viala, Alain Dabadie, Emmanuel Mas, Alain Lachaux, Lioara Restier-Miron, Laurent Michaud, Centre Technique Interprofessionnel des Oléagineux, des Protéagineux et du Chanvre (CETIOM), CHU Pontchaillou [Rennes], CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Pôle Médico-Chirurgical de Pédiatrie et de Génétique Clinique, Aix Marseille Université (AMU), Département de pédiatrie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hôpital Necker, Terres Inovia, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Robert Debré, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospices Civils de Lyon (HCL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Adolescent ,[SDV]Life Sciences [q-bio] ,Esophageal and Gastric Varices ,Capsule Endoscopy ,Sensitivity and Specificity ,Gastroenterology ,Esophageal capsule endoscopy ,03 medical and health sciences ,0302 clinical medicine ,Esophageal varices ,Internal medicine ,Hypertension, Portal ,medicine ,Humans ,Endoscopy, Digestive System ,Child ,Prospective cohort study ,business.industry ,Reproducibility of Results ,Gastric varices ,medicine.disease ,Predictive value ,3. Good health ,030220 oncology & carcinogenesis ,Portal hypertension ,Female ,030211 gastroenterology & hepatology ,France ,business ,Varices - Abstract
Background Esophagogastroduodenoscopy (EGD) is the standard method for diagnosis of esophageal and gastric varices in children. In this prospective study we evaluated the use of PillCam esophageal capsule endoscopy (ECE) in pediatric patients. Methods Patients aged 7 to 18 years presenting with portal hypertension and/or cirrhosis underwent ECE (PillCam ESO 2, Given Imaging Ltd.) followed by EGD. Results 102 patients were screened, 81 (52 boys; mean age 13.96 ± 0.25 years) were included and 21 were excluded (16 for “candy test” failure). Esophageal varices were identified by EGD in 62 patients (77 %) and by ECE in 57 patients (70 %) using the de Franchis classification (DFC). The sensitivity of ECE for esophageal varices was 92 % and the specificity was 100 % using DFC. Based upon 57/81 patients with small, medium, and large varices on both ECE and EGD, using DFC, the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were 55 %, 92 %, 89 %, and 63 %, respectively, giving a total overall accuracy of 72 %. To improve sensitivity and specificity in classification of esophageal varices, we propose using a modified score. This score detected esophageal varices with 100 % sensitivity, 93 % specificity, 94 % PPV, and 100 % NPV, giving a total overall accuracy of 97 %. All patients preferred ECE over EGD. No capsule retention was recorded. Conclusions ECE is a well-tolerated and safe procedure in children. Using the modified score, the sensitivity of ECE is currently sufficient to detect esophageal varices and replace EGD in infants with suspicion of esophageal varices or when EGD is refused.
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- 2018
48. A systematic review and meta-analysis of paediatric inflammatory bowel disease incidence and prevalence across Europe
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John Williams, Christos Tzivinikos, Corina Pienar, Stephen E. Roberts, Ilse Broekaert, Ann John, Marc A. Benninga, Nikhil Thapar, Rok Orel, Kym Thorne, Emmanuel Mas, Mike Thomson, Erasmo Miele, Jernej Dolinsek, Sian Morrison-Rees, Carmen Ribes-Koninckx, Roberts, S. E., Thorne, K., Thapar, N., Broekaert, I., Benninga, M. A., Dolinsek, J., Mas, E., Miele, E., Orel, R., Pienar, C., Ribes-Koninckx, C., Thomson, M., Tzivinikos, C., Morrison-Rees, S., John, A., Williams, J. G., Swansea University, Great Ormond Street Hospital for Children [London] (GOSH), King Saud University [Riyadh] (KSU), Queensland Children's Hospital, Partenaires INRAE, University Children's Hospital, Emma Children's Hospital, University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Naples Federico II, University Medical Centre Slovenia, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitario y Politécnico La Fe, Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, and European Society for Paediatric Gastroenterology Hepatology and Nutrition
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Pediatrics ,medicine.medical_specialty ,Population ,Disease ,Cochrane Library ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Prevalence ,medicine ,Humans ,030212 general & internal medicine ,Child ,Prospective cohort study ,education ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Incidence ,Gastroenterology ,General Medicine ,medicine.disease ,Ulcerative colitis ,3. Good health ,Europe ,Paediatric ,Meta-analysis ,Colitis, Ulcerative ,030211 gastroenterology & hepatology ,Trends ,business ,Needs Assessment ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background and AimsInflammatory bowel disease [IBD] is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states.MethodsWe undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018.ResultsIncidence rates for both paediatric Crohn’s disease [CD] and ulcerative colitis [UC] were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30.ConclusionsThe incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north–south than an east–west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.
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- 2020
49. Corrigendum to: Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study
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Olivier Alibeu, P. Tounian, Nadia Siala, Michela Tempia-Caliera, Jean-Pierre Hugot, Sabine Rakotobe, Christelle Lenoir, Anne Breton, Caterina Strisciuglio, Víctor Manuel Navas-López, Jan Melek, Alain Fischer, Frédéric Rieux-Laucat, Marie-Claude Stolzenberg, Eric Jeziorski, Yago González-Lama, Bénédicte Pigneur, Mongi Ben Hariz, Marina Aloi, Sylvain Latour, Fabienne Mazerolles, Christian Breuer, Julie Bruneau, Clara Crémilleux, Cecile Pelatan, Vaidotas Urbonas, Alexandre Fabre, Nadine Cerf-Bensussan, Frank M. Ruemmele, Luisa Mearin, Capucine Picard, Georgia Malamut, Neslihan Gurcan, Anders Paerregaard, Isabel Pinto Pais, Dan Turner, István Máttyus, Julie Rebeuh, Jiri Bronsky, Sylvain Hanein, Peter Lewindon, Rémi Duclaux-Loras, Graziella Guariso, Anne Bourrier, Odul Egritas Gurkan, Janos Major, Stéphanie Willot, Mara Cananzi, Marianna Parlato, Claudio Romano, Alain Lachaux, Matjaz Homan, Jorge Amil Dias, Eva Lévy, A Fischer, Stéphanie Coopman, Jan Krzysztof Nowak, Fernando Magro, Clémentine Dumant-Forest, Stephan Buderus, Bernadette Bègue, Fabienne Charbit-Henrion, Olivier Goulet, Evi Karanika, Alain Dabadie, Emmanuel Mas, Marta German Diaz, Cécile Fourrage, Rosa Lima, Charbit-Henrion, Fabienne, Parlato, Marianna, Hanein, Sylvain, Duclaux-Loras, Rémi, Nowak, Jan, Begue, Bernadette, Rakotobe, Sabine, Bruneau, Julie, Fourrage, Cécile, Alibeu, Olivier, Rieux-Laucat, Frédéric, Lévy, Eva, Stolzenberg, Marie-Claude, Mazerolles, Fabienne, Latour, Sylvain, Lenoir, Christelle, Fischer, Alain, Picard, Capucine, Aloi, Marina, Dias, Jorge Amil, Hariz, Mongi Ben, Bourrier, Anne, Breuer, Christian, Breton, Anne, Bronsky, Jiri, Buderus, Stephan, Cananzi, Mara, Coopman, Stéphanie, Crémilleux, Clara, Dabadie, Alain, Dumant-Forest, Clémentine, Gurkan, Odul Egrita, Fabre, Alexandre, Fischer, Aude, Diaz, Marta German, Gonzalez-Lama, Yago, Goulet, Olivier, Guariso, Graziella, Gurcan, Neslihan, Homan, Matjaz, Hugot, Jean-Pierre, Jeziorski, Eric, Karanika, Evi, Lachaux, Alain, Lewindon, Peter, Lima, Rosa, Magro, Fernando, Major, Jano, Malamut, Georgia, Mas, Emmanuel, Mattyus, Istvan, Mearin, Luisa M, Melek, Jan, Navas-Lopez, Victor Manuel, Paerregaard, Ander, Pelatan, Cecile, Pigneur, Bénédicte, Pais, Isabel Pinto, Rebeuh, Julie, Romano, Claudio, Siala, Nadia, Strisciuglio, Caterina, Tempia-Caliera, Michela, Tounian, Patrick, Turner, Dan, Urbonas, Vaidota, Willot, Stéphanie, Ruemmele, Frank M, and Cerf-Bensussan, Nadine
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VEO-IBD ,business.industry ,Yield (finance) ,monogenic IBD ,next generation sequencing ,very early onset IBD ,Gastroenterology ,Inflammatory Bowel Diseases ,Genetics and molecular epidemiology ,Original Articles ,General Medicine ,monogenic disorders ,Bioinformatics ,Very early onset ,DNA sequencing ,paediatrics ,Editor's Choice ,Multicenter study ,TNGS ,Medicine ,genetics and molecular epidemiology ,business - Abstract
Background and Aims An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.
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- 2020
50. Mantle Deformation Processes During the Rift‐To‐Drift Transition at Magma‐Poor Margins
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Nicholas J. Montiel, Emmanuel Masini, Luc Lavier, Othmar Müntener, and Sylvain Calassou
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rifting ,seafloor spreading ,numerical modeling ,seismic study ,mantle deformation ,Ivory Coast ,Geophysics. Cosmic physics ,QC801-809 ,Geology ,QE1-996.5 - Abstract
Abstract The rift‐to‐drift transition at rifted margins is an area of active investigation due to an incomplete understanding of the spatial and temporal evolution of physical and chemical processes at the ocean‐continent transition (OCT). Deep structures that characterize modern OCTs are often difficult to identify by seismic observations, while terrestrial exposures are preserved in fragments separated by tectonic discontinuities. Numerical modeling is a powerful method for contextualizing physical processes and observations relevant to rifted margin evolution. We synthesize results from geological observations of fossil OCTs preserved in ophiolites, a recent seismic experiment on the Ivorian margin, and numerical modeling to characterize mantle deformation and melt production for magma‐poor margins. Across varied surface heat fluxes, mantle potential temperatures, and extension rates, our model results show homologies with geological observations. We propose that the development of large shear zones in the mantle, melt infiltration, grain size reduction, and anastomosing detachment faults control the structure of OCTs. We also infer that a hot, upwelling, melt‐rich asthenosphere is an important control on the local stress environment. During the exhumation phase, continentward‐dipping shear zones couple with seaward‐dipping detachment faults to exhume the subcontinental and formerly asthenospheric mantle. The mantle forms core‐complex‐like domes of peridotite at or near the surface. The faults that exhume these peridotite bodies are largely anastomosing and exhibit magmatic accretion in their footwalls. A combination of magmatic accretion and volcanic activity derived from the shallow melt region constructs the oceanic lithosphere in the footwalls of the out‐of‐sequence continentward‐dipping detachment faults in the oceanic crust and subcontinental mantle.
- Published
- 2023
- Full Text
- View/download PDF
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