9 research outputs found

    Software Analysis: A point of view of a car manufacturer

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    International audienceThis paper presents a point of view on the way and works that Renault considers as necessary to insure a good level of software quality through the application of solutions concerning static code analysis and intrusive control of the software development by quality requirements and software verification levels to the supplier

    Identification of a novel bacterial strain with potentially beneficial probiotic properties in irritable bowel syndrome

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    International audienceIrritable bowel syndrome (IBS) is a functional disorder causing recurrent abdominal pain associated with changes in bowel habits. It is the most common disorder of gut-brain interaction diagnosed in gastroenterology and has a worldwide prevalence of 9.2% [1].Its etiology involves complex interactions of factors such as altered immune and barrier functions of the mucosa, central nervous system dysregulation of gut signaling and microbial dysbiosis within the gut. Modulating the gut microbiota, as a means of alleviating symptoms may therefore be an attractive prevention and treatment option. Indeed probiotics, which are live microorganisms that, when administered in adequate amounts confer a health benefit on the host [2], were shown to be beneficial in terms of improvement of global IBS symptoms [3], however the effects are strain specific.In this context, we developed a methodology combining in vitro and in vivo tests to maximize the probability of identifying novel strains with probiotic effects in IBS. We screened a collection of 41 strains of lactic acid bacteria. Bacterial supernatants were analyzed for the production of short chain fatty acids (SCFAs) and aryl hydrocarbon receptor (AhR) agonists, using gas chromatography and HepG2 Lucia reporter cell line, respectively. The strains were also tested in vitro for cytokine production after co-incubation on TNF-α challenged HT-29 cells or non-stimulated peripheral blood mononuclear cells (PBMCs). Additionally, measurements of transepithelial electrical resistance (TEER) of TNF-α challenged Caco-2 cells co-incubated with the strains were performed to test the improvement of barrier function. We then used principal component analysis (PCA) to identify new strains with profiles similar to those of bacteria with proven probiotic effect [4], [5] [6] and found a promising strain called PI41. This strain was then tested in a rodent model of IBS induced by infection with Citrobacter rodentium[7]. After pathogen clearance (16 days post infection), mice were administered per os daily with PI41 or saline buffer for the control group. The PI41 strain was able to resolve colonic hypersensitivity as measured by colorectal distention (CRD) test. This result correlated with an increase of AhR agonists in mice feces. This strain is therefore promising as a new probiotic to prevent and treat IBS

    From In Vitro to In Vivo: A Rational Flowchart for the Selection and Characterization of Candidate Probiotic Strains in Intestinal Disorders

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    International audienceExperimental and clinical evidence has demonstrated the potential of probiotic strains in the prevention or treatment of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). However, there is little data on what the methodology leading to the identification of such strains should be. In this work, we propose a new flowchart to identify strains with probiotic potential for the management of IBS and IBD, which we tested on a collection of 39 lactic acid bacteria and Bifidobacteria strains. This flowchart included in vitro tests of immunomodulatory properties on intestinal and peripheral blood mononuclear cells (PBMCs), assessment of the barrier-strengthening effect by measuring transepithelial electric resistance (TEER) and quantification of short-chain fatty acids (SCFAs) and aryl hydrocarbon receptor (AhR) agonists produced by the strains. The in vitro results were then combined in a principal component analysis (PCA) to identify strains associated with an anti-inflammatory profile. To validate our flowchart, we tested the two most promising strains identified in the PCA in mouse models of post-infectious IBS or chemically induced colitis to mimic IBD. Our results show that this screening strategy allows the identification of strains with potential beneficial effects on colonic inflammation and colonic hypersensitivity

    New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions

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    International audiencePurposeNew multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients’ quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain.MethodsA consensus report was established by neuroradiologists and neurologists from the French Observatory of MS, which aimed at reducing the number of Gd injections required during MS patient follow-up.RecommendationsThe French Observatory of MS recommends the use of macrocyclic Gd enhancement at time of diagnosis, when a new DMT is introduced, at 6-month re-baseline, and when previous scans are unavailable for comparison. Gd administration can be performed as an option in case of relapse or suspicion of intercurrent disease such as progressive multifocal leukoencephalopathy. Other follow-up MRIs do not require contrast enhancement, provided current and previous MRI acquisitions follow the same standardized protocol including 3D FLAIR sequences

    The radiologically isolated syndrome: revised diagnostic criteria

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    International audienceThe radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the central nervous system within individuals lacking symptoms typical of multiple sclerosis. The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfill 3-4 of 4 criteria for 2005 dissemination in space [DIS] and subjects fulfilling only 1 or 2 lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. 747 subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled 1 or 2 2017 DIS criteria (designated as Group 1 and Group 2, respectively), and 496 (66.4%) fulfilled 3 or 4 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS Group and were more likely to develop new T2 lesions over time (p < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to multiple sclerosis. At five years, the cumulative probability for a clinical event was 29.0% for Groups 1-2 compared to 38.7% for 2009-RIS (p = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at five years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (p < 0.001). The 2009-RIS subjects or Group 1-2 with at least 2 of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria

    Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study

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