Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort

International audienceBackground: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). Aims: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. Methods: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41 months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. Results: Only 53.5% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the 9 participating centres (27.3% to 70.0%, p= < 0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (47.6% vs 68.5%, p=< 0.0001). Independent predictors of colonoscopic surveillance were male sex, UC IBD subtype, longer disease duration, previous history of CRC, and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 70.7%, 26.6 and 30.0% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. Conclusions: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

BACKGROUND: The cellular prion protein, PrP(C), is GPI anchored and abundant in lipid rafts. The absolute requirement of PrP(C) in neurodegeneration associated to prion diseases is well established. However, the function of this ubiquitous protein is still puzzling. Our previous work using the 1C11 neuronal model, provided evidence that PrP(C) acts as a cell surface receptor. Besides a ubiquitous signaling function of PrP(C), we have described a neuronal specificity pointing to a role of PrP(C) in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C11(5-HT)) or noradrenergic (1C11(NE)) derivatives. METHODOLOGY/PRINCIPAL FINDINGS: The neuronal specificity of PrP(C) signaling prompted us to search for PrP(C) partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrP(C) with an 80 kDa protein identified by mass spectrometry as the tissue non-specific alkaline phosphatase (TNAP). This interaction occurs in lipid rafts and is restricted to 1C11-derived neuronal progenies. Our data indicate that TNAP is implemented during the differentiation programs of 1C11(5-HT) and 1C11(NE) cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C11(5-HT) and 1C11(NE) bioaminergic cells by controlling pyridoxal phosphate levels. Finally, TNAP activity is shown to modulate the phosphorylation status of laminin and thereby its interaction with PrP. CONCLUSION/SIGNIFICANCE: The identification of a novel PrP(C) partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrP(C) and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrP(C)-laminin interplay. The partnership between TNAP and PrP(C) in neuronal cells may provide new clues as to the neurospecificity of PrP(C) function

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Les patientes consultant en médecine générale sont-elles satisfaites de leur contraception ?

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

The behaviour household as regards a municipal solid waste financed by payt system

The PAYT system (pay as you throw) for financing the municipal solid waste (MSW) is a new economic tool to improve the management of MSW in Europe and tested in France. The economic analysis was applied on a local authority where the tariff is based on the number of wheeled bin emptying. We observe a decrease over 40% of the amount of residual waste, an increase of packaging collected and a development of prevention (temporal analysis). The meaning is a new behaviour of citizens regarding their waste to reach a lower payment. To explain, we intend to present the data analysis of a sample survey of the population and the results of an econometric model to evaluate the reaction of households in relation with the level of fees. We have distinguished three types of explanatory variables : sociological, economical as income households and technical linked with the frequency of collection, composting garden, civic amenity. Illegal diversions, as compaction waste in bin or burning in garden or illegal dumping, are not a reason to renounce the PAYT system. More than 90% of surveyed population approve the system

Etude de définition et d'impact de la redevance incitative au tri des emballages ménagers

Ce présent rapport de recherche étudie l'influence de la redevance incitative sur le système d`élimination des déchets ménagers, impacts sur les bilans matière et financier, et sur les comportements des citoyens. Les modélisations, côté «offre» et côté «demande» sont présentées avec leurs résultats d'application sur deux groupements de communes l'ayant mis en oeuvre. Ces applications ont donné lieu à des simulations des flux financiers et à des tests économétriques du modèle comportemental sur les données d'une enquête de terrain. Ce rapport aboutit à des recommandations destinées aux collectivités locales désireuses de mettre en place la redevance incitative comme moyen de financement du service d'élimination des déchets ménagers et de développement du tri et de la prévention des déchets

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

International audienceThe cellular prion protein, PrPC, is a glycosylphosphatidylinositol-anchored protein, abundant in lipid rafts and highly expressed in the brain. While PrPC is much studied for its involvement under its abnormal PrPSc isoform in Transmissible Spongiform Encephalopathies, its physiological role remains unclear. Here, we report that GSK3β, a multifunctional kinase whose inhibition is neuroprotective, is a downstream target of PrPC signalling in serotonergic neuronal cells. We show that the PrPC-dependent inactivation of GSK3β is relayed by a caveolin-Lyn platform located on neuronal cell bodies. Furthermore, the coupling of PrPC to GSK3β potentiates serotonergic signalling by altering the distribution and activity of the serotonin 1B receptor (5-HT1BR), a receptor that limits neurotransmitter release. In vivo, our data reveal an increased GSK3β kinase activity in PrP-deficient mouse brain, as well as sustained 5-HT1BR activity, whose inhibition promotes an anxiogenic behavioural response. Collectively, our data unveil a new facet of PrPC signalling that strengthens neurotransmission

Widening exposome exploration by means of complementary HRMS analytical platforms: use case on pesticide exposure

International audienceHuman exposure to food and environmental contaminants (such as pesticides) is generally estimated by indirect methods. Targeted bio-monitoring is a way to assess the internal exposure on a limited number of substances, needing large sample amounts for analyses as rigorous and sensitive as possible. Thus, the human health risks associated with multi-exposure to complex mixtures currently remain under-explored.In this context, the SCREENPEST project aims at providing a unified methodology for large-scale characterisation of human internal exposure to pesticides, via a "suspect profiling" approach, using urine

Widening exposome exploration by means of complementary HRMS analytical platforms: use case on pesticide exposure

International audienceHuman exposure to food and environmental contaminants (such as pesticides) is generally estimated by indirect methods. Targeted bio-monitoring is a way to assess the internal exposure on a limited number of substances, needing large sample amounts for analyses as rigorous and sensitive as possible. Thus, the human health risks associated with multi-exposure to complex mixtures currently remain under-explored.In this context, the SCREENPEST project aims at providing a unified methodology for large-scale characterisation of human internal exposure to pesticides, via a "suspect profiling" approach, using urine