Maternal Genome-Wide DNA Methylation Patterns and Congenital Heart Defects

The majority of congenital heart defects (CHDs) are thought to result from the interaction between multiple genetic, epigenetic, environmental, and lifestyle factors. Epigenetic mechanisms are attractive targets in the study of complex diseases because they may be altered by environmental factors and dietary interventions. We conducted a population based, case-control study of genome-wide maternal DNA methylation to determine if alterations in gene-specific methylation were associated with CHDs. Using the Illumina Infinium Human Methylation27 BeadChip, we assessed maternal gene-specific methylation in over 27,000 CpG sites from DNA isolated from peripheral blood lymphocytes. Our study sample included 180 mothers with non-syndromic CHD-affected pregnancies (cases) and 187 mothers with unaffected pregnancies (controls). Using a multi-factorial statistical model, we observed differential methylation between cases and controls at multiple CpG sites, although no CpG site reached the most stringent level of genome-wide statistical significance. The majority of differentially methylated CpG sites were hypermethylated in cases and located within CpG islands. Gene Set Enrichment Analysis (GSEA) revealed that the genes of interest were enriched in multiple biological processes involved in fetal development. Associations with canonical pathways previously shown to be involved in fetal organogenesis were also observed. We present preliminary evidence that alterations in maternal DNA methylation may be associated with CHDs. Our results suggest that further studies involving maternal epigenetic patterns and CHDs are warranted. Multiple candidate processes and pathways for future study have been identified

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/)

L'expérience patient : la construction des compétences des malades atteints d'hémopathies malignes par les dispositifs hospitaliers

Cette recherche s'intéresse à l'expérience des patients atteints d'hémopathies malignes. A partir d'un dispositif d'enquête qualitatif associant des observations ethnographiques et des entretiens, elle s'attache à rendre compte de la façon dont les dispositifs d'un hôpital spécialisé dans la lutte contre le cancer et les professionnels de santé vont construire des compétences autour de cette expérience de malade. Ce travail identifie d'une part les modes de coordination entre les soignants et les soignés pour saisir les différents contextes et processus par lesquels les compétences des patients sont actualisées, mises en veille, renforcées, transformées et refreinées par les dispositifs hospitaliers (consultations, programme d'ETP, dispositif de suivi téléphonique, etc.). Par la suite nous appréhendons la trajectoire de maladie (au sens de Anselm L. Strauss) des patients dans les dispositifs hospitaliers, en lien avec les processus de sélection et d'auto-régulation des soignés, qui sous-tendent leur engagement (au sens de Howard S. Becker) dans une approche éducative. Il s'agit d'apporter un regard sociologique sur la façon dont les patients s'engagent ou non dans ces dispositifs et dans ces champs de compétences. Nous nous sommes attachés à décrire les effets de la pluralité des compétences, des caractéristiques sociales (âge, sexe, catégorie socio-économique et professionnelle, situation familiale, etc.) et de la trajectoire de maladie (moment du parcours de soin et ruptures en rapport à l'évolution de la maladie, incidences sur la carrière professionnelle, sur la vie familiale, etc.) du patient qui les porte, sur ses logiques d'actions et notamment son engagement dans les dispositifs hospitaliers à plus ou moins long terme.This research focuses on the experience of patients with malignant hemopathies. Based on a qualitative survey combining ethnographic observations and interviews, it aims to describe the way mechanisms of a cancer treatment center and health professionals build skills around the experience of being ill. On the one hand, this work identifies the methods of coordination between healthcare providers and patients in order to understand the different contexts and processes according to which patients' competences are updated, put on hold, reinforced, transformed and reframed by the hospital systems (consultations, TPE program, telephone follow-up system, etc.). On the other hand, we examine the trajectory of illness (in the sense of Anselm L. Strauss) of patients in hospital mechanisms, in relation to the processes of selection and self-regulation of patients, which underlie their commitment (in the sense of Howard S. Becker) to an educational approach. The aim is to provide a sociological perspective on the way patients do or do not engage in these mechanisms and fields of competences. We wish to describe the effects of the plurality of competences, social characteristics (age, sex, socio- economic and professional category, family situation, etc.) and of the trajectory of illness (moment in the care pathway and breaks in relation to the evolution of the illness, impact on the professional career, on family life, etc.) of the patient who bears them, on his or her ways to act and in particular his or her commitment to hospital mechanisms over a longer or shorter term

Patient experience : building the competences of patients with malignant hemopathies through hospital mecanisms

Cette recherche s'intéresse à l'expérience des patients atteints d'hémopathies malignes. A partir d'un dispositif d'enquête qualitatif associant des observations ethnographiques et des entretiens, elle s'attache à rendre compte de la façon dont les dispositifs d'un hôpital spécialisé dans la lutte contre le cancer et les professionnels de santé vont construire des compétences autour de cette expérience de malade. Ce travail identifie d'une part les modes de coordination entre les soignants et les soignés pour saisir les différents contextes et processus par lesquels les compétences des patients sont actualisées, mises en veille, renforcées, transformées et refreinées par les dispositifs hospitaliers (consultations, programme d'ETP, dispositif de suivi téléphonique, etc.). Par la suite nous appréhendons la trajectoire de maladie (au sens de Anselm L. Strauss) des patients dans les dispositifs hospitaliers, en lien avec les processus de sélection et d'auto-régulation des soignés, qui sous-tendent leur engagement (au sens de Howard S. Becker) dans une approche éducative. Il s'agit d'apporter un regard sociologique sur la façon dont les patients s'engagent ou non dans ces dispositifs et dans ces champs de compétences. Nous nous sommes attachés à décrire les effets de la pluralité des compétences, des caractéristiques sociales (âge, sexe, catégorie socio-économique et professionnelle, situation familiale, etc.) et de la trajectoire de maladie (moment du parcours de soin et ruptures en rapport à l'évolution de la maladie, incidences sur la carrière professionnelle, sur la vie familiale, etc.) du patient qui les porte, sur ses logiques d'actions et notamment son engagement dans les dispositifs hospitaliers à plus ou moins long terme.This research focuses on the experience of patients with malignant hemopathies. Based on a qualitative survey combining ethnographic observations and interviews, it aims to describe the way mechanisms of a cancer treatment center and health professionals build skills around the experience of being ill. On the one hand, this work identifies the methods of coordination between healthcare providers and patients in order to understand the different contexts and processes according to which patients' competences are updated, put on hold, reinforced, transformed and reframed by the hospital systems (consultations, TPE program, telephone follow-up system, etc.). On the other hand, we examine the trajectory of illness (in the sense of Anselm L. Strauss) of patients in hospital mechanisms, in relation to the processes of selection and self-regulation of patients, which underlie their commitment (in the sense of Howard S. Becker) to an educational approach. The aim is to provide a sociological perspective on the way patients do or do not engage in these mechanisms and fields of competences. We wish to describe the effects of the plurality of competences, social characteristics (age, sex, socio- economic and professional category, family situation, etc.) and of the trajectory of illness (moment in the care pathway and breaks in relation to the evolution of the illness, impact on the professional career, on family life, etc.) of the patient who bears them, on his or her ways to act and in particular his or her commitment to hospital mechanisms over a longer or shorter term

Le suivi en maison de naissance : une liberté de choix pour les femmes ? Une approche sociologique

France has legalized the experimentation of birth centres in 2013, after 20 years of negotiations about the existence of these structures, while in several European countries or in North America they have been existing for forty years now. This late legalization happens in a context of debate and questioning over birth concentration in nursing hospital structures. In this context, women's choices for their low-risk pregnancy's follow-up and delivery are restricted to types I, II and III maternity units. Despite that, a minority of women has opted for birth centres, a still undeveloped alternative structure in France. The objective of this study is to determine the motivations which led women to make this choice by a sociological approach. Fifteen semi-directed interviews were then conducted with women at Ile-de-France region's two birth centres: the CALM birth centre and Pontoise's birth centre. We then showed that these women, regardless of the birth centre where they were being followed, were looking for a de-medicalization of their pregnancy follow-up and delivery and for care by one single midwife. However it seemed obvious that women were mostly looking for emancipation against medical power and demanding respect for their desires and their freedom of choice. But, is this choice really free if it’s made out of spite or if it is underpinned by economic arguments?La France a légalisé l’expérimentation des maisons de naissance en 2013 après une vingtaine d’années de négociations autour de ces structures, alors même que dans plusieurs pays européens ou nord-américains elles existent depuis quarante ans déjà. Cette légalisation tardive arrive dans un contexte où la concentration de la naissance dans des structures hospitalières médicalisées est contestée et où le choix des femmes pour le suivi de leur grossesse à bas risque et l’accouchement est restreint aux maternités de type I, II et III. Malgré cela, une minorité de femmes ont fait le choix des maisons de naissance, structure alternative encore peu développée en France. L’objectif de cette étude, qui s’inscrit dans une perspective sociologique, est de déterminer les motivations des femmes qui les ont menées à faire ce choix. Quinze entretiens semi-directifs ont été réalisés auprès de femmes inscrites dans les deux maisons de naissance de la région Ile-de-France : la maison de naissance du CALM et la maison de naissance de Pontoise. Nous avons alors montré que ces femmes, quelle que soit la maison de naissance où elles étaient suivies, étaient à la recherche d’une démédicalisation de leur suivi et de leur accouchement et d’un accompagnement par une même sage-femme d’une part. Cependant, cette étude montre que les femmes étaient surtout à la recherche d’une émancipation face au pouvoir médical, à la revendication d’un respect de leurs désirs et d’une liberté de choix. Mais ce choix est-il vraiment libre lorsqu’il est fait par dépit ou s’il est sous-tendu par des arguments économiques contraignants

Xavier Bioy (dir.), La régulation publique des centres de ressources biologiques : le cas des tumorothèques

Cet ouvrage collectif appréhende la régulation publique des tumorothèques. Ces biobanques constituent un ensemble intégrant des collections d’échantillons biologiques de pathologies cancéreuses et de tissus sains, des données personnelles associées, le savoir-faire des professionnels qui manipulent les échantillons et des bases de données permettant le traitement et le stockage de l’ensemble de ces informations. Depuis le règlement général sur la protection des données (RGPD) du 25 mai 2018, ..

(Re)production des inégalités intériorisées en oncologie

International audienceGABORIT(1), Charlotte BRUNEAU(2), Jean-paul GÉNOLINI(3), Philippe TERRAL(4) deployed by some patients to the detriment of others. Moreover, these same patients become spokespersons for a system that is beneficial to them.Cet article vise à rapprocher les problématiques de littératie en santé de celles concernant les inégalités sociales et territoriales sous l’angle des inégalités épistémiques. À partir de l’étude d’un programme d’éducation thérapeutique pour des patients sous anticancéreux oraux, nous analysons les conditions de participation des patients et de visibilité de leurs savoirs. Les entretiens individuels et les ateliers collectifs du programme, tout comme son format pédagogique, sont autant d’espaces d’interactions qui valorisent ou occultent des expériences de patients. À ce titre, deux ans d’observation des ateliers et 23 entretiens nous permettent de mettre en relation l’activité des participants et le contexte institutionnel dans lequel se déroulent les interactions. Certains profils de patients porteurs de compétences bien spécifiques en matière de littératie sont plus engagés/à l'aise que d’autres et plus valorisés/visibilisés dans ce dispositif d’ETP du fait de la dynamique des interactions entre soignants et patients et entre patients. Outre des conditions de recrutement au sein du programme, nous observons des formes d’auto-sélection dans les ateliers. Les soignants participent à la valorisation des compétences en littératie déployées par certains patients au détriment d’autres. En outre, ces mêmes patients se font porte-parole d’un dispositif qui leur est favorable

Packing simulation and analysis applied to a thermoplastic composite recycling process

International audienceA numerical model of packing applied to rigid objects is presented. It aims at describing a random stack of polymer composite chips in order to model the packing step of an existing recycling technique. The geometric properties of the stack play a major role in the mechanical properties of the recycled products. Short, simple and effective geometric descriptors of the stack are proposed. Their ability to differentiate random stacks is illustrated with an example. Then, a validation is proposed based on experimental data obtained from a bench specially designed for this work. The tests consist in the free fall of square chips. Finally, the developed model is compared to other models (free fall and packing of fibers) in order to enforce its relevance in the simulation of packing of rigid objects

Determinants of physical activity commitment in adolescents and young adults with cancer: sociological protocol for a hospital-based mixed methods study (ETAPE-AJA)

International audienceIntroduction Adolescents and young adults (AYA) with cancer undergo physical transformations due to disease and treatments occurring alongside puberty and adolescence. Although physical activity is recommended for its benefits, its practice among AYA with cancer remains insufficient. The aim of the Éducation Thérapeutique et Activité Physique: Engagement des Adolescents et Jeunes Adultes atteints de cancer study is to identify the evolution of AYA with cancer medical knowledge and powers (power to act, to express oneself) over life and cancer care, and their role in commitment in adapted physical activity (APA) and therapeutic patient education during and after oncological treatments. Methods and analysis This prospective mixed methods monocentre study will be conducted in a French comprehensive cancer centre. Observations will be conducted two times a week during medical consultations, APA interventions and therapeutic education sessions for AYA with cancer. Semidirective interviews will involve 70 participants, including AYA with cancer aged 15–25, health professionals, APA teachers and parents. Quantitative data will be collected on AYA’s social characteristics and participation in physical activity intervention and therapeutic education sessions. A correspondence factor analysis will supplement inductive analysis of ethnographic qualitative data, involving patient coresearchers. The results will help to improve the understanding of AYAs’ medical knowledge and powers, their commitment in physical activity and to develop strategies to increase their participation. Ethics and dissemination This study complies with reference methodology MR004 of the French National Data Protection Authority and was registered by the Data Protection Officer of the Leon Berard Cancer Center on the activity registry of the institution (Ref. N°R201-004-259; 5 July 2022). Ethics approval has been obtained from the Centre Léon Bérard ethics board (Ref. N°2022–006; 20 July 2022). Oral informed consent will be obtained from all participants before data collection. The results of this study will be published in peer-reviewed scientific journals, national and international conferences

Arabinoxylans and inulin modulate the luminal and mucosa-associated bacteria in vitro and in vivo

There is increasing interest in gastro-intestinal microbiology to improve the balance between putative beneficial and harmful commensal microbiota. Mucosal microbes make closer contact with the host than luminal ones and could therefore more strongly affect host health. A short term in vitro adhesion assay was used to examine initial mucin colonisation by bacteria derived from the mixed microbial community of the ascending colon of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Further, long term prebiotic effects on the luminal and mucosa-associated microbial community (MAMC) were assessed in vitro and in vivo with respectively the SHIME and gnotobiotic rats. During the short term experiment, adhesion capacity differed substantially between bacteria and decreased from lactobacilli over faecal coliforms, bifidobacteria and clostridia to total anaerobes. In addition, intestinal water lowered adhesion compared to phosphate buffered saline. By processing the data to an Adhesion Related Prebiotic Index (AR-PI), it was found that intestinal water stimulated adherence of positive commensals. Arabinoxylans (AX) decreased the bacterial adhesion capacity (matrix independently), whereas inulin had less or no influence. During the long term experiment, group-specific DGGE analysis showed that although inoculated with the same human faecal microbiota, the in vivo and in vitro model both harbour distinct microbial communities. Both carbohydrates were shown to exert long term prebiotic effects on the luminal and mucosal microbial community. Interestingly, AX induced a shift towards a specific Bifidobacterium sp, both in the in vitro and in vivo model. The developed methodologies could be useful for the characterisation of the relevant but barely investigated mucosa-associated microbial community in health and disease (e.g. IBD) as well as for its modulation with functional foods like prebiotics