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STUDY QUESTION Are persistent organic pollutants (POPs) associated with a diminished ovarian reserve (DOR) in women of reproductive age? SUMMARY ANSWER Amongst 17 POPs detected in over 20% of serum samples, only p,p′-DDE was significantly associated with an increased risk of DOR, and β-hexachlorocyclohexane (β-HCH) was significantly associated with a decreased risk of DOR whilst mixture analyses yielded non-significant associations and did not detect any interactions between POPs. WHAT IS KNOWN ALREADY Animal studies have shown that several POPs can alter folliculogenesis and increase follicle depletion. However, only a few studies have been conducted in humans, with small sample sizes and inconsistent results. STUDY DESIGN, SIZE, DURATION Our study included 138 cases and 151 controls from the AROPE case–control study. Study participants were women between 18 and 40 years of age recruited amongst couples consulting for infertility in four fertility centres in western France between 2016 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Cases of DOR were defined as women with anti-Müllerian hormone (AMH) levels ≤1.1 ng/ml and/or antral follicle count (AFC) MAIN RESULTS AND THE ROLE OF CHANCE Of the 43 POPs, 17 were detected in over 20% of the serum samples. In the single-exposure multivariate logistic regressions, p,p′-DDE (median 165.0 IQR 161.0 ng/l in controls) as a continuous exposure was significantly associated with an increased risk of DOR (odds ratio (OR) 1.39, 95% CI 1.10–1.77) and non-significantly associated with an increased risk of DOR for the second and third terciles (OR 1.46, 95% CI 0.74–2.87, and OR 1.72, 95% CI 0.88–3.37, respectively). β-HCH (median 24.2 IQR 21.5 ng/l in controls) was significantly associated with a decreased risk of DOR when β-HCH was treated as a continuous exposure (OR 0.63, 95% CI 0.44–0.89) and for the third tercile of exposure (OR 0.43, 95% CI 0.21–0.84) and non-significantly associated with a decreased risk of DOR for the second tercile (OR 0.77, 95% CI 0.42–1.42). All sensitivity analyses confirmed our results. BKMR showed similar associations for single exposures but found no significant associations for the total mixture effect. In addition, the BKMR results did not suggest any interactions between POPs. LIMITATIONS, REASONS FOR CAUTION Controls were recruited amongst infertile couples and thus may not be representative of all women of reproductive age. However, their POP concentrations were in the same range as in the general French population. WIDER IMPLICATIONS OF THE FINDINGS This study is the first to examine the associations between serum POPs and DOR. The well-recognized anti-androgenic properties of p,p′-DDE and estrogenic properties of β-HCH could explain these associations of opposite direction. If these results are replicated elsewhere, this could have an impact on fertility prevention messages and help in understanding the impact of POPs on the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Fondation de France (grant numbers 2014-50537 and 00110196) and the French Biomedicine Agency (2016). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

International audience; The aim was to describe out-of-hospital cardiac arrest (OHCA) occurring in the workplace of a large emergency network, and compare the evolution of their management in the last 15 years. A retrospective study based on data from the Northern Alps Emergency Network compared characteristics of OHCA between cases in and out the workplace, and between cases occurring from January 2004 to December 2010 and from January 2011 to December 2017. Among the 15,320 OHCA cases included, 320 occurred in the workplace (2.1%). They were more often in younger men, and happened more frequently in an area with access to public defibrillation, had more often a shockable rhythm, had a cardiopulmonary resus-citation started by a bystander more frequently, and had a better outcome. Cardiopulmonary resusci-tation started by a bystander was the only chain of survival link that improved for cases occurring after December 2010. Workplace OHCA seems to be managed more effectively than others; however, only a slight survival improvement was observed, suggesting that progress is still needed. (c) 2023 Occupational Safety and Health Research Institute, Published by Elsevier Korea LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

International audience; Introduction: With recent higher awareness of the necessity of improving healthcare workers' well-being, we aimed to overview systematic reviews dealing with interventions on well-being, occupa-tional health, and aging of healthcare workers. Methods: From three databases (PubMed, Embase, and Web of Science), a scoping review of systematic reviews was carried out to determine current knowledge on interventions focused on the well-being or aging of healthcare workers. Only systematic reviews were considered, with appropriate extraction and quality evaluation. Results: Of the total of 445 references identified, 10 systematic reviews were included, mostly published since 2019. Nurses were the most frequent targets of interventions, and mental health was the main outcome described. The overall level of quality was also heterogenous, with high to low-quality reviews. Conclusions: Workers' mental health well-being was the major outcome targeted by intervention, with varying level of evidence. Further studies are needed with integrative approaches on global health and life course perspectives, with a focus on the plurality of settings, worker types, and women. (c) 2022 THE AUTHORS. Published by Elsevier BV on behalf of Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency. This is an open access article under the CC BY -NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Purpose Upstream social marketers advocate implementing effective public policies to protect vulnerable populations from the impacts of advertising harmful products. This study aims to explore how alcohol ad content restrictions (as practised in some countries where ads may only convey factual information and objective properties of alcohol products) versus non-regulated advertising affect consumers’ product perceptions, attitude towards the ad and desire to drink. This study also examines how such restrictions influence the noticeability of text health warnings in ads (signalling alcohol-related risks) depending on their prominence. Design/methodology/approach A multi-method study was used to increase the validity of results. An online quantitative survey (n = 348) and an eye-tracking study (n = 184) were conducted on young French people (15–30). The eye-tracking method is particularly relevant for objectively measuring visual attention. Findings Results show that content restrictions on alcohol advertising reduce ad appeal and desire to drink. A more prominent format enhanced attentional processing of the text warning, whereas none of the tested ad contents influenced its noticeability. Practical implications This study assesses scientific evidence of the effect on alcohol ad content regulations adopted by some countries and provides arguments for upstream social marketers to inform and influence policymakers. Originality/value To the best of the authors’ knowledge, this is the first multi-method study that assesses the effect of regulated vs non-regulated alcohol ads in terms of persuasion and of text warning visibility.

International audience; BACKGROUND: Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient’s drug metabolism capacity. OBJECTIVES: Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm. PATIENTS AND METHODS: Sixty-one patients treated with VRC were prospectively included in the study, and VRC and NOX levels were assayed by LC-MS/MS. A mixed logistic model on repeated measures was implemented to analyze risk factors for the patient’s concentration to be outside the therapeutic range. RESULTS: Based on 225 measurements, the median and interquartile range were 2.4 μg/mL (1.2; 4.2), 2.1 μg/mL (1.5; 3.0), and 1.0 (0.6; 1.9) for VRC, NOX, and the MR, respectively. VRC C(min) 1.15 and

International audience; BACKGROUND: Prenatal lead exposure is known to have neurotoxic effects on the developing fetus, while some viral infections may have a tropism for the central nervous system. Our objective was to study whether the effects of prenatal lead exposure on infant development and behaviors at 18 months of age are modified by the occurrence of a maternal infection to Zika virus (ZIKV) during pregnancy. METHODS: During the ZIKV epidemic in Guadeloupe in 2016 a cohort of pregnant women was set up. Blood samples (pregnancy, childbirth and cord) (n = 297) enabled us to measure blood lead levels aimed to determine prenatal lead exposure and the likelihood of maternal infection during pregnancy (ZIKV status + vs -). The 18 months "Ages and Stages Questionnaire" (ASQ) was used to generate scores for global development, fine and gross motor skills, communication, problem solving, and personal-social skills. The questions from a longitudinal cohort study conducted in Canada (Québec) were used to generate hyperactivity, opposition, inattention and physical aggression scores. Associations were tested by multivariate linear regressions. RESULTS: Prenatal lead exposure was associated with delays in neurodevelopment at 18 months, reflected by lower scores in ASQ totals, and in the fine motor and problem-solving domains. Some of these associations appeared to be sex-specific, observed almost exclusively in boys (ASQ total, fine motor and personal-social scores). Prenatal lead exposure was not associated with behavioral scores. ZIKV infection during pregnancy was associated with a lower fine motor ASQ score, and higher scores for hyperactivity, opposition and physical aggression. Significant interaction between prenatal lead exposure and ZIKV status was observed with a lower personal-social score in ZIKV (-) only, and for hyperactivity and inattention scores, though some of these interactions (ASQ personal-social score, inattention score) were no longer significant when children with microcephaly were excluded from the analyses. DISCUSSION/CONCLUSION: Our study confirms previous findings of associations between prenatal exposure to lead at low levels and adverse neurodevelopmental outcomes during infancy and the particular vulnerability of boys. It suggests associations between ZIKV infection during pregnancy and adverse effects on a number of neurodevelopmental functions (fine motor function) and behaviors (opposition, hyperactivity), that need to be confirmed at later age. There is no strong evidence of interaction between ZIKV infection and lead exposure but both prenatal risk factors may affect fine motor function.

Background: Scientific evidence and public health reports keep highlighting the continuous and alarming worldwide progression of physical inactivity and sedentary behaviors in children and adolescents. The present paper summarizes findings from the 2022 French Report Card (RC) on physical activity for children and youth and compares them to the 2016, 2018, and 2020 RCs. Methods: The 2022 edition of the French RC follows the standardized methodology established by the Active Healthy Kids Global Matrix. Ten physical activity indicators have been evaluated and graded based on the best available evidence coming from national surveys, peer-reviewed literature, government and nongovernment reports, and online information. The evaluation was also performed in children and adolescents with disabilities. Indicators were graded from A (high level of evidence) to F (very low level of evidence) or INC for incomplete. Results: The evaluated indicators received the following grades: overall physical activity: D−; organized sport participation and physical activity: C; active play: F; active transportation: C; sedentary behaviors: D−; family and peers: D; physical fitness: C; school: C−; community and the built environment: F; government: B. Conclusions: While this 2022 French RC shows progression for 7 out of the 10 indicators considered, it also underlines the continuous need for actions at the local, regional, and national levels to develop better surveillance systems and favor a long-term improvement of youth movement behaviors.

International audience; Introduction: Primary spontaneous pneumothorax (PSP) is the presence of air in the pleural space, occurring in the absence of trauma and known lung disease. Standardized expert guidelines on PSP are needed due to the variety of diagnostic methods, therapeutic strategies and medical and surgical disciplines involved in its management. Methods: Literature review, analysis of literature according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology; proposals for guidelines rated by experts, patients, and organizers to reach a consensus. Only expert opinions with strong agreement were selected. Results: A large PSP is defined as presence of a visible rim along the entire axillary line between the lung margin and the chest wall and superior or equal to 2 cm at the hilum level on frontal chest x-ray. The therapeutic strategy depends on the clinical presentation: emergency needle aspiration for tension PSP; in the absence of signs of severity: conservative management (small PSP), needle aspiration or chest tube drainage (large PSP). Outpatient treatment is possible if a dedicated outpatient care system is previously organized. Indications, surgical procedures and perioperative analgesia are detailed. Associated measures, including smoking cessation, are described. Conclusion: These guidelines are a step towards PSP treatment and follow-up strategy optimization in France.; Introduction : Le pneumothorax spontané primaire (PSP) est un épanchement gazeux dans la cavité pleurale, survenant hors traumatisme et pathologie respiratoire connue. Des recommandations formalisées d'experts sur le sujet sont justifiées par les pluralités de moyens diagnostiques, stratégies thérapeutiques et disciplines médicochirurgicales intervenant dans leur prise en charge. Méthodes : Revue bibliographique, analyse de la littérature selon méthodologie GRADE (Grading of Recommendation Assessment, Development and Evaluation) ; propositions de recommandations cotées par experts, patients et organisateurs pour obtenir un consensus. Seuls les avis d'experts avec accord fort ont été retenus. Résultats : Un décollement sur toute la hauteur de la ligne axillaire et supérieur ou égal à 2 cm au niveau du hile à la radiographie thoracique de face définit la grande abondance. La stratégie thérapeutique dépend de la présentation clinique : exsufflation en urgence pour PSP suffocant ; en l'absence de signe de gravité : prise en charge conservatrice (faible abondance), exsufflation ou drainage (grande abondance). Le traitement ambulatoire est possible si organisation en amont de la filière. Les indications, procédures chirurgicales et l'analgésie périopératoire sont détaillées. Les mesures associées, notamment le sevrage tabagique, sont décrites. Conclusion : Ces recommandations sont une étape de l'optimisation des stratégies de traitement et de suivi des PSP en France.

International audience; BackgroundComplementary therapy in oncology aims to help patients better cope with the illness and side effects (SEs) of cancer treatments that affect their quality of life (QOL). This study aimed to assess the benefits of homeopathic treatment on the health-related QOL (HRQOL) of patients with non-metastatic breast cancer (BC) prescribed in post-surgical complementary therapy.Patients and methodsAn extraction from the French nationwide healthcare database targeted all patients who underwent mastectomy for newly diagnosed BC between 2012 and 2013. HRQOL was proxied by the quantity of medication used to palliate the SEs of cancer treatments.ResultsA total of 98,009 patients were included (mean age: 61 ± 13 years). Homeopathy was used in 11%, 26% and 22% of patients respectively during the 7–12 months before surgery, the 6 months before, and 6 months after. Thereafter, the use remained stable at 15% for 4 years. Six months after surgery, there was a significant overall decrease (RR = 0.88, confidence interval (CI)95 = 0.87–0.89) in the dispensing of medication associated with SEs in patients treated with ≥ 3 dispensing of homeopathy compared to none. The decrease appeared to be greater for immunostimulants (RR = 0.79, (CI)95 = 0.74–0.84), corticosteroids (RR = 0.82, (CI)95 = 0.79–0.85), and antidiarrheals (RR = 0.83, (CI)95 = 0.77–0.88).ConclusionThe study showed an increasing use of homeopathy in patients with BC following diagnosis. This use was maintained after surgery and seemed to play a role in helping patients to better tolerate the SEs of cancer treatments.Micro-abstractThis study evaluated the benefits of homeopathy on the quality of life (QOL) of patients with non-metastatic breast cancer (BC). There is an increasing use of homeopathy in patients with BC after diagnosis, leading to an overall decrease in medications that palliate the side effects of cancer treatment. This may indicate that QOL is improved in patients with BC who use homeopathy.

International audience; Aims: To evaluate the effectiveness of a French mass-media campaign in raising knowledge of both long-term alcohol-related harms (LTH) and low-risk drinking guidelines (LRDG), as well as in lowering alcohol consumption.Design: An 8-month longitudinal survey from February to October 2019, with three waves of on-line data collection (T0 before the campaign, T1 just after it ended and T2 6 months after it ended).Setting: France.Participants: A total of 2538 adult drinkers (aged 18-75 years).Measurements: The main outcomes' variables were LTH knowledge (cancer, hypertension, brain haemorrhage), LRDG knowledge (two guidelines: 'maximum of two drinks a day' and 'minimum of 2 days without alcohol per week'), intention to reduce alcohol consumption and self-declared consumption with respect to the French LRDG. At T1, exposure to the campaign was measured using self-reported campaign recall.Findings: In T1, we observed significant positive interactions between exposure group based on campaign recall and survey waves on knowledge of (i) the 'maximum two drinks a day' guideline [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.08-1.62, P = 0.008], (ii) brain haemorrhage (aOR = 1.80, 95% CI = 1.44-2.25, P < 0.001) and (iii) hypertension (aOR = 1.41, 95% CI = 1.09-1.81, P = 0.008) risks. Campaign exposure was also associated with a significant decrease in at-risk drinking in women (aOR = 0.67, 95% CI = 0.50-0.88, P = 0.004). No significant interaction was observed at T1 for the knowledge of the 'minimum of 2 days without alcohol a week' guideline, or of cancer risk. At T2, no significant interaction was observed for the main outcomes' variables.Conclusions: There appears to be an association between exposure to a 2019 French mass-media campaign to raise knowledge of long-term alcohol-related harms and low-risk drinking guidelines and reduce alcohol consumption and (i) improved knowledge of the 'maximum two drinks per day guideline', (ii) knowledge of the risks of hypertension and brain haemorrhage and (iii) a reduction in the proportion of people exceeding low-risk drinking guidelines (in the general population only). These associations were only observed over the short term and, in some cases, only for certain segments of the population.

National audience; Objective: The aim of this article is to review the current state of knowledge on the effect of psychosocial factors (PSF) on the occurrence of occupational accidents (OA). Methods: Three data sources (Pubmed, Science direct and Web of science) were used to identify articles published over the period 2000–2021, reporting the results of longitudinal or cross-sectional epidemiological studies. Results: Since the 2000s and especially since 2010, the number of studies on the effect of PSF on the occurrence of OA has been steadily increasing. The most explored psychosocial dimensions are poor social relationships at work and work intensity, and to a lesser extent autonomy and emotional demands. The literature seems to confirm the role of these dimensions on the occurrence of OA. On the other hand, the job insecurity and conflicts of values as determinant of OA are the purpose of only a few epidemiological studies. Similarly, the effects of joint exposure to PSF and physical factors on the risk of OA are rarely studied. Conclusion: Psychosocial factors, in particular those relating to poor social relationships and work intensity, are essential factors to be taken into account in the occurrence of OA. However, the relationships between the other psychosocial dimensions and OA remain to be explored. There is a real need for longitudinal epidemiological studies on the subject. In addition, the effects of co-exposure between physical and psychosocial risk factors on the occurrence of OA should be considered more closely for better targeted prevention. © 2022 Elsevier Masson SASObjectif: Cet article a pour objectif de faire un état des lieux des connaissances sur l'effet des facteurs psychosociaux (FPS) sur la survenue d'accident du travail (AT). Méthodes: Trois sources de données (Pubmed, Science direct et Web of science) ont été interrogées pour identifier les articles publiés sur la période 2000–2021, relatant les résultats d’études épidémiologiques longitudinales ou transversales. Résultats: Depuis les années 2000 et surtout depuis 2010, le nombre d’études portant sur l'effet des FPS sur la survenue d'AT est en constante augmentation. Les dimensions psychosociales les plus explorées quant à leur rôle dans la survenue d'AT sont les rapports sociaux dégradés au travail et l'intensité du travail, puis dans une moindre mesure l'autonomie et les exigences émotionnelles. La littérature semble confirmer le rôle de ces dimensions dans la survenue d'AT. En revanche, l'insécurité de la situation du travail et les conflits de valeurs comme déterminants d'AT ne font l'objet que de rares études épidémiologiques. De même, les effets des expositions conjointes des FPS et des facteurs physiques sur le risque d'AT ne sont que rarement étudiés. Conclusion: Les facteurs psychosociaux, en particulier ceux relatifs aux rapports sociaux dégradés et à l'intensité du travail, sont des facteurs essentiels à prendre en compte dans la survenue des AT. Les relations entre certaines autres dimensions psychosociales et les AT restent cependant à explorer. Il y a un réel besoin d’études épidémiologiques longitudinales sur le sujet. De plus, les effets des co-expositions entre les facteurs de risque physiques et psychosociaux sur la survenue d'AT devraient être davantage considérés, afin de permettre une prévention mieux adaptée. © 2022 Elsevier Masson SAS

International audience; The anti-Müllerian hormone (AMH) is a heterodimeric glycoprotein belonging to the TGFb superfamily implicated in human embryonic development. This hormone was first described as allowing regression of the epithelial embryonic Müllerian structures in males, which would otherwise differentiate into the uterus and fallopian tubes. It activates a signaling pathway mediated by two transmembrane receptors. Binding of AMH to its receptor induces morphological changes leading to the degeneration of Müllerian ducts. Recently, new data has shown the role played by this hormone on structures other than the genital tract. If testicular AMH expression decreases in humans over the course of a lifetime, synthesis may persist in other tissues in adulthood. The mechanisms underlying its production have been unveiled. The aim of this review is to describe the different pathways in which AMH has been identified and plays a pivotal role.

International audience; BackgroundLocal governments are well-positioned to promote healthy behaviours and environments. In France, since 2009, this role can be reinforced by signature of a Local Health Contract with the Regional Health Agency. This multi-year scheme includes an action plan which may cover four areas: health promotion, disease prevention, health care and long-term care. Although approximately 400 Local Health Contracts had been signed by 2018, we found only sparse evidence on the context in which they were formulated and the contents of their action plans. Based on the international literature, the CLoterreS study aimed to develop an instrument characterizing the contracts’ action plans, with a specific focus on prevention and health promotion. This paper presents an assessment and application of the CLoterreS instrument.MethodsThe instrument was developed and applied in five steps: 1) development of the contextual and thematic variables; 2) pre-testing of a coding chart and its coding guide; 3) consultation with practitioners; 4) assessment of inter-rater agreement; and 5) application of the instrument to a nationally-stratified random sample of 53 contracts.ResultsWhile inter-rater agreement by type of variables was satisfactory (κ > 0.7), some variables had to be discarded due to lack of information or insufficient agreement. The analysis indicates that most of the 53 contracts studied were signed in urban areas, on the scale of a single town or a syndicate of municipalities. The action plans are clearly focused on life circumstances, health promotion and protection or primary prevention of diseases, insofar as, on average, 73% of the contracts’ action forms address at least one of these topics. The proportion of action forms dealing with at least one topic in secondary or tertiary prevention, long-term care or the organisation of health care and services is nevertheless substantial (43%). Illustrations of actions are presented.ConclusionBuilding on internationally recognized evidence-based practice, the CLoterreS instrument has proven useful in characterizing health promotion action plans at the local level. Its use by practitioners could foster a broader vision of the scope of actions that can be implemented through a Local Health Contract and in conjunction with other local prevention and access-to-care schemes.; ContexteLes collectivités locales sont bien placées pour promouvoir des comportements et des environnements favorables à la santé. En France, depuis 2009, ce rôle peut être renforcé par la signature d'un Contrat local de santé (CLS) avec l'Agence régionale de santé. Ce dispositif pluriannuel inclut un plan d'action pouvant aborder quatre domaines : promotion de la santé, prévention des maladies, soins, accompagnement médico-social. Malgré environ 400 CLS recensés en 2018, les connaissances sur leur contexte d’élaboration et le contenu de leurs plans d'action restent limitées. En s'appuyant sur la littérature internationale, l’étude CLoterreS visait à développer un outil permettant de caractériser les CLS selon leurs plans d'action, notamment en matière de prévention et de promotion de la santé. Dans cet article nous présentons une évaluation et une application de l'outil CLoterreS.MéthodeL'outil a été développé et appliqué en cinq étapes : 1) le développement de variables contextuelles et thématiques ; 2) le prétest de la grille de codage et de son guide ; 3) la consultation de professionnels ; 4) un test d'accord inter-juges ; et 5) l'application et l'utilisation de l'outil à partir d'un échantillon aléatoire stratifié à l’échelle nationale de 53 CLS.RésultatsLe test d'accord inter-juges par type de variable était satisfaisant (κ > 0,7), mais certaines variables ont dû être écartées par manque d'information ou faute d'accord suffisant. L'analyse indique que la plupart des 53 CLS étudiés ont été signés en milieu urbain, à l’échelle d'une municipalité ou d'une intercommunalité. Les plans d'action sont clairement orientés vers les circonstances de vie, la promotion et la protection de la santé ou la prévention primaire des maladies, dans la mesure où, en moyenne, 73 % des fiches action abordent au moins un thème relevant de ce domaine. La proportion de fiches action abordant au moins un thème relevant de la prévention secondaire ou tertiaire, de l'accompagnement médico-social ou de l'organisation de soins et services de santé est néanmoins substantielle (43 %). Des exemples d'action sont présentés.ConclusionS'appuyant sur des pratiques probantes reconnues à l’échelle internationale, l'outil CLoterreS s'est avéré utile pour caractériser des plans d'action en promotion de la santé au niveau local. Son utilisation par des professionnels pourrait encourager une vision plus large de la diversité d'actions pouvant être mises en œuvre dans un CLS et en lien avec d'autres dispositifs locaux de prévention et d'accès aux soins.

Background: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson’s disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. Objective: Our objective was to develop a predictive model combining clinical scores and imaging. Methods: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual values Results: Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p

International audience; Like in many countries, the French health authorities are pinning their hopes on vaccination to stop the spread of the COVID-19 pandemic. However, this requires the public to get the vaccine. Based on six COCONEL surveys carried out during and after the lockdown among the general French adult population, which aimed to explore life conditions during this period and individual perceptions of the situation, this paper aims to investigate the acceptability of a putative vaccine against COVID-19 among the French population, and more specifically to compare attitudes among the elderly, who are more vulnerable to the disease, with those of younger people. Out of the 8,036 respondents, 27.5% declared that they would refuse the vaccine if it were available. Among the age groups of particular interest, 29.2% of people aged 18–64 said they would refuse the vaccine, compared to 12.4% of respondents aged 65 or over. For both groups, this refusal rate fluctuated depending on the date of the survey, gender, household composition, level of household income, and uptake of the last flu vaccine. In conclusion, more attention should be paid to elderly people, as they were more likely to report hostility toward vaccination in general. Finally, considering that several vaccines are now available, further studies should be done to study vaccine uptake in relation to the vaccine offered.; La campagne vaccinale contre la COVID-19 est une priorité sanitaire. Toutefois, l’adhésion de la population française à cette vaccination est un élément clé de sa réussite. À la lumière de six enquêtes COCONEL réalisées en population générale adulte pendant et après le confinement dans l’objectif de documenter les conditions de vie des Français pendant cette période ainsi que leur perception des mesures mises en place par les autorités, cet article propose d’analyser l’intention de se faire vacciner des Français à l’égard d’une vaccination contre la COVID-19, selon l’âge. Plus spécifiquement, l’intention des personnes âgées de 65 ans et plus, particulièrement vulnérables face à cette maladie, comparativement aux personnes plus jeunes. Parmi les 8 036 répondants, 27,5 % refuseraient ce vaccin s’il était disponible ; 29,2 % des 18-64 ans contre 12,4 % des 65 ans et plus. Quel que soit l’âge, ce refus de vaccination varie selon la date d’enquête, mais aussi selon le genre, la composition du foyer, le niveau de revenus, ainsi que la pratique vaccinale antérieure contre la grippe saisonnière. En conclusion, une attention particulière devra être portée aux personnes âgées de 65 ans et plus qui sont plus enclines à manifester une hostilité à la vaccination en général. Enfin, la mise sur le marché de différents vaccins devrait encourager à poursuivre les analyses de l’adhésion vaccinale au regard du vaccin proposé.

Many health care professionals are dealing with the issue of transgender people in their medical practice. In the field of reproduction, Trans people can benefit from fertility preservation before the introduction of hormonal treatment or surgery altering their fertility. This article, which is the result of a collaborative work of several reproductive professionals involved in the health of Trans people, provides an overview of the possibilities of fertility preservation and medically assisted reproduction techniques in France for Trans people., Un nombre croissant de personnes en transition sollicitent les centres autorisés à la préservation de la fertilité en vue de conserver leurs gamètes. Il est actuellement recommandé d’informer les personnes Trans sur leur fertilité actuelle et future, et de leur proposer une congélation de gamètes si leur fertilité est à risque d’être altérée par la prise d’un traitement hormonal ou la réalisation d’une chirurgie sur les gonades. Cet article est issu du travail collaboratif de plusieurs professionnels de la Reproduction impliqués dans la prise en charge des personnes Trans. Il propose un état des lieux des possibilités actuelles en préservation de fertilité et de l’utilisation des gamètes congelés/décongelés en France pour les personnes Trans.

International audience

International audience; Data sharing is gradually becoming a requirement across all fields of science, owing to its key benefits in verifying the reproducibility of findings and reusing existent data for new purposes. Although meta-research studies are complex, time-consuming and hinge on the availability of data produced and curated by others, there has been little focus on how they make their own data available. This is in stark contrast with the heightened attention data sharing has received in clinical research. Yet, as secondary data users par excellence, meta-researchers are ethically bound to both improving and evaluating data sharing practices, as well as correctly sharing their own data. We contrast particularities of data sharing in meta-research and clinical research, such as benefits, barriers, inadequate and potentially pervasive sharing practices. We conclude with an array of concrete and tailored recommendations for improvement.

International audience; In female mammals, the oviduct and uterus are essential sites for female and male gamete transport, fertilization, implantation, and maintenance of a successful pregnancy. To delineate the reproductive function of Mothers against decapentaplegic homolog 4 (Smad4), we specifically inactivated Smad4 in ovarian granulosa cells and, oviduct and uterine mesenchymal cells using the Amhr2-cre mouse line. Deletion of exon 8 of Smad4 results in the production of an MH2-truncated SMAD4 protein. These mutant mice are infertile due to the development of oviductal diverticula and defects during the implantation process. The ovaries are fully functional as demonstrated in an ovary transfer experiment. The development of oviductal diverticula occurs shortly after puberty and is dependent on estradiol. The diverticula interfere with sperm migration and embryo transit to the uterus, reducing the number of implantation sites. Analysis of the uterus shows that, even if implantation occurs, decidualization and vascularization are defective resulting in embryo resorption as early as the seventh day of pregnancy. Thus, Smad4 plays an important function in female reproduction by controlling the structural and functional integrity of the oviduct and uterus.

International audience; BACKGROUND: Combined effect of both prenatal and early postnatal exposure to ambient air pollution on child cognition has rarely been investigated and sensitive periods of sensitivity are unknown. This study explores the temporal relationship between pre- and postnatal exposure to PM(10), PM(2.5), NO(2) and child cognitive function. METHODS: Using validated spatiotemporally resolved exposure models, pre- and postnatal daily PM(2.5), PM(10) (satellite based, 1 km resolution) and NO(2) (chemistry-transport model, 4 km resolution) concentrations at the mother’s residence were estimated for 1271 mother-child pairs from the French EDEN and PELAGIE cohorts. Scores representative of children’s General, Verbal and Non-Verbal abilities at 5-6 years were constructed based on subscale scores from the WPPSI-III, WISC-IV or NEPSY-II batteries, using confirmatory factor analysis (CFA). Associations of both prenatal (first 35 gestational weeks) and postnatal (60 months after birth) exposure to air pollutants with child cognition were explored using Distributed Lag Non-linear Models adjusted for confounders. RESULTS: Median exposure from conception until the 60th month of life was 19.3 μg/m(3) for PM(10), 12.4 μg/m(3) for PM(2.5) and 16.9 μg/m(3) for NO(2). Increased maternal exposure to both PM(10) and PM(2.5) between the 5th and the 11th gestational weeks was related to higher General, Verbal and Non-verbal abilities among males. On the contrary, increased maternal exposure to PM(10) between the 22nd and 29th gestational weeks was associated with lower General and Non-verbal abilities among males. Similar trends were observed for PM(2.5). No significant sensitive exposure windows were detected for postnatal exposure, NO(2) or among females. DISCUSSION: These results suggest poorer cognitive development among males at 5-6 years following increased maternal exposure to PM(10) during mid-pregnancy. Apparent protective associations observed for early prenatal exposure to PM(10) and PM(2.5) are unlikely to be causal and might be due to live birth selection bias.

International audience; Qualifiée d’« urgence de santé publique de portée internationale » par l’OMS en août 2014, l’épidémie à virus Ebola, en raison de sa diffusion rapide longtemps hors de contrôle et d’un potentiel létal élevé, a généré un désastre sanitaire de grande ampleur. L’épidémie a comptabilisé plus de 11 000 décès pour 28 421 cas déclarés, et entraîné d’autres décès, indirects et non comptabilisés, du fait du chaos dans lequel les structures de santé étaient plongées. En première ligne, le corps des professionnels de santé a été durement affecté, avec plus de 400 décès. L’épidémie a particulièrement sévi en Guinée, au Libéria et en Sierra Léone, pays parmi les plus pauvres d’Afrique de l’Ouest et fortement déstabilisés par des crises politiques récentes. Dans une moindre mesure, elle a affecté le Nigéria, le Mali et plus marginalement le Sénégal. (Intro.)

International audience; BACKGROUND: An important issue for young men affected by testicular germ cell tumor (TGCT) is how TGCT and its treatment will affect, transiently or permanently, their future reproductive health. Previous studies have reported that xenobiotics can induce changes on human sperm epigenome and have the potential to promote epigenetic alterations in the offspring. OBJECTIVES: Here, we report the first longitudinal DNA methylation profiling of frozen sperm from a TGCT patient before and up to 2 years after a bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: A TGCT was diagnosed in a 30-year-old patient. A cryopreservation of spermatozoa was proposed before adjuvant BEP treatment. Semen samples were collected before and after chemotherapy at 6, 9, 12, and 24 months. The DNA methylation status was determined by RRBS to detect DNA differentially methylated regions (DMRs). RESULTS: The analysis revealed that among the 74 DMRs showing modified methylation status 6 months after therapy, 17 remained altered 24 months after treatment. We next associated DMRs with differentially methylated genes (DMGs), which were subsequently intersected with loci known to be important or expressed during early development. DISCUSSION AND CONCLUSION: The consequences of the cancer treatment on the sperm epigenome during the recovery periods are topical issues of increasing significance as epigenetic modifications to the paternal genome may have deleterious effects on the offspring. The altered methylated status of these DMGs important for early development might modify their expression pattern and thus affect their function during key stages of embryogenesis, potentially leading to developmental disorders or miscarriages.

International audience; OBJECTIVES: Influenza vaccination is recommended for healthcare workers (HCWs). However, in a 1500-bed tertiary care university hospital in France, influenza vaccine coverage among HCWs was 23% in 2017. PATIENTS AND METHODS: We performed a cross-sectional study between 05/09/2018 and 25/09/2018 among HCWs, randomly selected independent of their vaccination status, to estimate influenza vaccination coverage rate during the 2017-2018 season, and explore factors influencing vaccination, using a questionnaire. Multivariable regression analysis to assess factors associated with vaccine uptake and hierarchical clustering on principal components to identify HCW profiles regarding factors influencing vaccine uptake, were performed after multiple imputation. RESULTS: 977 HCWs were included (68% participation rate), primarily females (84%), nurses (38%) of 18-39 years old. Influenza vaccination coverage rate reached 33[30-36]%. Frequent vaccination (aOR 39.27[21.52-74.51]) and personal/family medical history of influenza (aOR 3.33[1.16-10.02]) were independently associated with vaccination. In HCWs’ patterns of influenza vaccination status, three clusters were identified: 1) (n = 438) mostly vaccinated (70%); 2) (n = 507) most unvaccinated (97%); and 3) (n = 32) unvaccinated HCWs lacking knowledge on influenza and influenza vaccine. Among the 148 (15%) HCWs reluctant to receive the vaccine the following year, 23 (16%) received it for the 2017-2018 season, while 125 (84%) did not, mostly stating they had doubts about the vaccine (82%). CONCLUSION: This work identifies determinants of vaccine uptake and highlights HCWs profiles associated with factors influencing vaccination and a subgroup of HCWs flexible about having the vaccine during the upcoming seasonal campaign. This result opens up perspectives toward improved vaccination coverage among HCWs.

International audience; Si quelques problématiques spécifiques au bâtiment sont très anciennes (peintures au plomb, amiante), la pollution intérieure ou, de façon plus positive, la qualité des environnements intérieurs s’est invitée dans l’arène scientifique puis le débat public depuis les années 1970. Du fait notamment de la prise de conscience du temps passé dans des environnements intérieurs et donc de l’importance de ces environnements en termes d’exposition, de nombreux travaux ont été menés pour améliorer les connaissances et définir des mesures de gestion et de prévention.

International audience; L’évaluation des risques décrite dans ce chapitre, au sens de Risk Assessment défini en 1983 par le National Research Council (NRC, 1983) est une analyse scientifique basée sur le recueil de données et la modélisation. Ses résultats sont des expressions qualitatives ou quantitatives de l’intensité et de la vraisemblance de dommages, causés par une exposition. L’évaluation s’effectue au niveau populationnel, car il ne s’agit pas de prédictions individuelles. Elle est la première composante de l’analyse des risques, qui comprend également la gestion et la communication des risques (OMS, 2021). Cet outil mobilise et organise les connaissances existantes pour aider à la décision publique, répondre à une question spécifique, guider la mise en œuvre de politiques publiques, ou la mise en place de réglementations protectrices de la santé.Si ce chapitre traite des composés chimiques, les concepts, principes et étapes de la démarche s’appliquent aussi aux risques physiques et biologiques. Après une présentation de ses objectifs, ce chapitre abordera les raisons d’être et les concepts de la démarche d’évaluation des risques sanitaires, puis en détaillera les étapes : formulation du problème, identification des dangers, établissement de la relation dose-réponse, évaluation des expositions et enfin caractérisation des risques et des incertitudes.

International audience; BACKGROUND: Several studies have reported that prenatal exposure to some persistent organic pollutants (POPs) is associated with higher adiposity in childhood. Few studies have assessed whether this finding persists into adolescence, and few have considered exposure to POPs as a mixture. This study aims to assess the association between prenatal exposure to multiple POPs and adiposity markers and blood pressure in preadolescents. METHODS: This study included 1667 mother-child pairs enrolled in the PELAGIE (France) and the INMA (Spain) mother-child cohorts. Three polychlorobiphenyls (PCB 138, 153 and 180, treated as a sum of PCBs) and three organochlorine pesticides (p,p’-Dichlorodiphenyldichloroethylene [p,p’-DDE], β-hexachlorocyclohexane [β-HCH], and hexachlorobenzene [HCB]) were assessed in maternal or cord serum. Body mass index z-score (zBMI), abdominal obesity (waist-to-height ratio > 0.5), percentage of fat mass, and blood pressure (mmHg) were measured at around 12 years of age. Single-exposure associations were studied using linear or logistic regressions, and the POP mixture effect was evaluated using quantile G-computation (qgComp) and Bayesian Kernel Machine Regression (BKMR). All models were adjusted for potential confounders and performed for boys and girls together and separately. RESULTS: Prenatal exposure to the POP mixture was associated with higher zBMI (beta [95 % CI] of the qgComp = 0.15 [0.07; 0.24]) and percentage of fat mass (0.83 [0.31; 1.35]), with no evidence of sex-specific association. These mixture effects were also statistically significant using BKMR. These associations were driven mainly by exposure to HCB and, to a lesser extent, to β-HCH. In addition, the single-exposure models showed an association between β-HCH and p,p’-DDE and higher systolic blood pressure, especially in girls (p,p’-DDE for girls = 1.00 [0.15; 1.86]). No significant associations were found for PCBs. CONCLUSION: This study suggests that prenatal exposure to POPs, particularly organochlorine pesticides, remains associated with unfavorable cardiometabolic health up to the age of 12.

International audience; L’épisode de choléra à Londres en 1849 lors duquel John Snow fut le premier à mettre en évidence un agrégat de cas autour d’un point d’eau contaminé est l’un des premiers jalons de la surveillance en hygiène environnementale (Astagneau et Ancelle, 2011). L’histoire de la surveillance s’inscrit d’abord dans la gestion des contacts des personnes ayant des maladies transmissibles graves (peste, typhus, variole, fièvre jaune, etc.) (Thacker et Birkhead, 2008). Ces maladies étaient associées à des éclosions rapides et à des taux de mortalité élevés. L’un des objectifs de la surveillance était alors de détecter précocement les cas pour les isoler et prévenir la propagation des maladies. À partir des années 1940, le docteur Langmuir et ses collègues ont développé une nouvelle vision de la surveillance en s’intéressant à l’incidence des maladies dans une population donnée plutôt qu’aux cas (le nombre absolu sans dénominateur), permettant ainsi la formalisation du concept de « surveillance sanitaire » (Langmuir, 1963).Depuis, l’adoption d’une vision holistique de la santé incluant les déterminants de santé que sont les facteurs personnels, sociaux, économiques et environnementaux a permis l’émergence de la surveillance dans d’autres sphères que celles des maladies transmissibles, comme les maladies chroniques d’origine environnementale ou encore différents événements de santé (accidents domestiques, tentatives de suicide…). Ce chapitre fait un tour d’horizon de la surveillance en santé environnementale, en présente les principaux concepts et l’illustre par des études de cas.

International audience; 23.1. Le milieu de travail : un déterminant majeur de la santé 23.2. Lésions professionnelles et indicateurs de santé 23.3. Principaux facteurs de risque pour les travailleurs 23.3.1. Agents chimiques 23.3.2. Agents biologiques 23.3.3. Agents physiques 23.3.4. Contraintes du travail associées aux troubles musculo-squelettiques (TMS) 23.3.5. Organisation du travail 23.4. Prévention et gestion du risque professionnel 23.4.1. Interventions en santé au travail 23.4.2. Surveillance des milieux de travail 23.4.3. Surveillance médicale individuelle 23.4.4. Surveillance épidémiologique 23.5. Perspectives

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International audience; Pesticides, pollution de l’air, de l’eau et des aliments, changements climatiques, menaces biologiques, chimiques, radiologiques, épidémies et inégalités environnementales de santé… Les sujets d’inquiétude quant aux conséquences de la dégradation de l’environnement sur notre santé sont nombreux et ont besoin d’être compris et analysés à l’aide des connaissances scientifiques actuelles. Unique dans le paysage éditorial et scientifique francophone, cet ouvrage présente les méthodes et approches de la santé publique environnementale d’aujourd’hui. Cette 2e édition s’enrichit de nouvelles perspectives comme la démarche « Une seule santé », le concept d’exposome, et offre une vision globale des impacts sanitaires des changements climatiques. Présentant les grands défis écologiques et les inégalités socio-environnementales de notre temps, plus de 150 auteurs s’appuient sur les données les plus récentes, établissent des objectifs au gré d’exemples illustrés et d’études de cas en Europe, en Afrique et en Amérique du Nord. Alors que les programmes axés sur la santé publique, la santé environnementale, la santé au travail et les sciences de l’environnement connaissent un engouement sans précédent, cet ouvrage est une référence pour les étudiants, enseignants, chercheurs et professionnels de ces disciplines, ainsi que pour les organisations publiques et associatives dans toute la francophonie. (R.A.)

International audience; Objectives: Pneumococcal immunization is recommended in dialysis patients. We aimed to estimate pneumococcal vaccination coverage among patients who initiate dialysis in France, and its association with mortality. Methods: Data were extracted from two prospective national databases, merged using a deterministic linkage method: renal epidemiology and information network (REIN) registry, which includes all patients on dialysis and kidney transplants recipients in France, and the national health insurance information system (SNIIRAM) which collects individual data on health expenditure reimbursement, including vaccines. We enrolled all patients who initiated chronic dialysis in 2015. Data on health status at dialysis initiation, dialysis modalities, and pneumococcal vaccine prescribed from 2 years before to 1 year after dialysis start were collected. Univariate and multivariate Cox proportional hazard models were used to assess one-year all-cause mortality. Results: Among the 8,294 incident patients included, 1,849 (22.3 %) received at least one pneumococcal vaccine before (n = 542, 6.5 %), or after (n = 1,307, 15.8 %) dialysis start, as follows: 13-valent pneumococcal conjugated vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23), n = 938 (50.7 %); only PPSV23, n = 650 (35.1 %); or only PCV13, n = 261 (14.1 %). Vaccinated patients were younger (mean, 66.5 ± 14.8 years vs. 69.0 ± 14.9 years, P ≤ 0.001), more likely to suffer from glomerulonephritis (17.0 % vs. 11.0 %, P ≤ 0.001), and less likely to start dialysis in emergency (27.2 % vs. 31.1 %, P = 0.001). On multivariate analysis, patients who received PCV13 and PPSV23, or only PCV13 were less likely to die (respectively, HR = 0.37; 95 %CI 0.28–0.51, and HR = 0.35; 95 %CI 0.19–0.65). Conclusions: Pneumococcal immunization with PCV13 followed by PPSV23, or with PCV13 alone, but not with PPSV23 alone, is independently associated with decreased one year-mortality in patients who start dialysis.

International audience; BackgroundSuccessive epidemic waves of COVID-19 illustrated the potential of SARS-CoV-2 variants to reshape the pandemic. Detecting and characterising emerging variants is essential to evaluate their public health impact and guide implementation of adapted control measures.AimTo describe the detection of emerging variant, B.1.640, in France through genomic surveillance and present investigations performed to inform public health decisions.MethodsIdentification and monitoring of SARS-CoV-2 variant B.1.640 was achieved through the French genomic surveillance system, producing 1,009 sequences. Additional investigation of 272 B.1.640-infected cases was performed between October 2021 and January 2022 using a standardised questionnaire and comparing with Omicron variant-infected cases.ResultsB.1.640 was identified in early October 2021 in a school cluster in Bretagne, later spreading throughout France. B.1.640 was detected at low levels at the end of SARS-CoV-2 Delta variant’s dominance and progressively disappeared after the emergence of the Omicron (BA.1) variant. A high proportion of investigated B.1.640 cases were children aged under 14 (14%) and people over 60 (27%) years, because of large clusters in these age groups. B.1.640 cases reported previous SARS-CoV-2 infection (4%), anosmia (32%) and ageusia (34%), consistent with data on pre-Omicron SARS-CoV-2 variants. Eight percent of investigated B.1.640 cases were hospitalised, with an overrepresentation of individuals aged over 60 years and with risk factors.ConclusionEven though B.1.640 did not outcompete the Delta variant, its importation and continuous low-level spread raised concerns regarding its public health impact. The investigations informed public health decisions during the time that B.1.640 was circulating.

International audience; Purpose: To evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa).Methods: A prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer's perspective, with a time horizon of 48 months. Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY). We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap.Results: Total costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: - 0.016 to 0.099).Conclusions: Treating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.

International audience; Premature ovarian insufficiency (POI) is a leading form of female infertility, characterised by menstrual disturbance and elevated follicle-stimulating hormone before age 40. It is highly heterogeneous with variants in over 80 genes potentially causative, but the majority of cases having no known cause. One gene implicated in POI pathology is TP63. TP63 encodes multiple p63 isoforms, one of which has been shown to have a role in the surveillance of genetic quality in oocytes. TP63 C-terminal truncation variants and N-terminal duplication have been described in association with POI, however, functional validation has been lacking. Here we identify three novel TP63 missense variants in women with nonsyndromic POI, including one in the N-terminal activation domain, one in the C-terminal inhibition domain, and one affecting a unique and poorly understood p63 isoform, TA*p63. Via blue-native page and luciferase reporter assays we demonstrate that two of these variants disrupt p63 dimerization, leading to constitutively active p63 tetramer that significantly increases the transcription of downstream targets. This is the first evidence that TP63 missense variants can cause isolated POI and provides mechanistic insight that TP63 variants cause POI due to constitutive p63 activation and accelerated oocyte loss in the absence of DNA damage.

International audience; BACKGROUND: Therapeutic management of relapsing-remitting multiple sclerosis (RRMS) has evolved towards early treatment. The objective was to assess the impact of early treatment initiation on disability progression among RRMS first-line treated patients. METHODS: This study included all incident RRMS cases starting interferon or glatiramer acetate for the first time from 1996/01/01 to 2012/31/12 (N=5,279) from ten MS expert OFSEP centers (Observatoire Français de la Sclérose en Plaques). The delay from treatment start to attain an irreversible Expanded Disability Status Scale score of 3.0 were compared between "Early" group (N= 1,882; treated within 12 months following MS clinical onset) and "Later" group using propensity score weighted Kaplan-Meier methods, overall and stratified by age. RESULTS: Overall, the restricted mean time before reaching EDSS 3.0 (RMST) from treatment start was 11 years and two months for patients treated within the year following MS clinical onset and 10 years and seven months for patients treated later. Thus, early treated patients gained 7 months (95% CI: [4-11] months) in the time to reach EDSS 3.0 compared to patients treated later (treatment start delayed by 28 months). The difference in RMST was respectively six months (95% CI: [1-10] months) and 14 months (95% CI: [4-24] months) in the "≤40 years" age group and in the ">40 years" age group, in favour of early group. . CONCLUSIONS: Early treatment initiation resulted in a significant reduction of disability progression among patients with RRMS, and also among older patients.

Objectives Staphylococcal infective endocarditis (IE) remains a hard-to-treat infection with high mortality. Both the evaluation of new innovative therapies and research on alternative models mimicking human IE are therefore urgently needed to improve the prognosis of patients with diagnosed IE. Dalbavancin is a novel anti-staphylococcal lipoglycopeptide but there are limited data supporting its efficacy on biofilm infections. This antibiotic could be an alternative to current therapies for the medical treatment of IE but it needs to be further evaluated. Methods Here we developed an original ex vivo model of Staphylococcus aureus IE on human heart valves and assessed biofilm formation on them. After validating the model, the efficacy of two antistaphylococcal antibiotics, vancomycin and dalbavancin, was compared by measuring and visualizing their respective ability to inhibit and eradicate late-formed biofilm. Results Determination of the minimum biofilm inhibitory (MbIC) and eradicating (MbEC) concentrations in our ex vivo model identified dalbavancin as a promising drug with much lower MbIC and MBEC than vancomycin (respectively Conclusions These data highlight a strong bactericidal effect of dalbavancin, particularly on an infected heart valve compared with vancomycin. Dalbavancin could be a realistic alternative treatment for the management of staphylococcal IE.

International audience; INTRODUCTION: Dominant-negative effects have been described for 10 F11 variants in the literature. AIM: The current study aimed at identifying putative dominant-negative F11 variants. MATERIAL AND METHODS: This research consisted in a retrospective analysis of routine laboratory data. RESULTS: In a series of 170 patients with moderate/mild factor XI (FXI) deficiencies, we identified heterozygous carriers of previously reported dominant-negative variants (p.Ser243Phe, p.Cys416Tyr, and p.Gly418Val) with FXI activities inconsistent with a dominant-negative effect. Our findings also do not support a dominant-negative effect of p.Gly418Ala. We also identified a set of patients carrying heterozygous variants, among which five out of 11 are novel, with FXI activities suggesting a dominant-negative effect (p.His53Tyr, p.Cys110Gly, p.Cys140Tyr, p.Glu245Lys, p.Trp246Cys, p.Glu315Lys, p.Ile421Thr, p.Trp425Cys, p.Glu565Lys, p.Thr593Met, and p.Trp617Ter). However, for all but two of these variants, individuals with close to half normal FXI coagulant activity (FXI:C) were identified, indicating an inconstant dominant effect. CONCLUSION: Our data show that for some F11 variants recognized has having dominant-negative effects, such effects actually do not occur in many individuals. The present data suggest that for these patients, the intracellular quality control mechanisms eliminate the variant monomeric polypeptide before homodimer assembly, thereby allowing only the wild-type homodimer to assemble and resulting in half normal activities. In contrast, in patients with markedly decreased activities, some mutant polypeptides might escape this first quality control. In turn, assembly of heterodimeric molecules as well as mutant homodimers would result in activities closer to 1:4 of FXI:C normal range.

Introduction The composite coverage index (CCI) is the weighted average coverage of eight preventive and curative interventions received along the maternal and childcare continuum. This study aimed to analyse maternal and child health indicators using CCI. Methods We performed a secondary analysis of demographic and health surveys (DHS) focused on women aged 15 to 49 and their children aged 1 to 4. This study took place in Guinea. The CCI (meeting the need for planning, childbirth assisted by qualified healthcare workers, antenatal care assisted by qualified healthcare workers, vaccination against diphtheria, pertussis, tetanus, measles and Bacillus Calmette-Guérin, taking oral rehydration salts during diarrhoea and seeking care for pneumonia) is optimal if the weighted proportion of interventions is > 50%; otherwise, it is partial. We identified the factors associated with CCI using the descriptive association tests, the spatial autocorrelation statistic and multivariate logistic regression. Results The analyses involved two DHS surveys, with 3034 included in 2012 and 4212 in 2018. The optimal coverage of the CCI has increased from 43% in 2012 to 61% in 2018. In multivariate analysis, in 2012: the poor had a lower probability of having an optimal CCI than the richest; OR = 0.11 [95% CI; 0.07, 0.18]. Those who had done four antenatal care visits (ANC) were 2.78 times more likely to have an optimal CCI than those with less OR = 2.78 [95% CI;2.24, 3.45]. In 2018: the poor had a lower probability of having an optimal CCI than the richest OR = 0.27 [95% CI; 0.19, 0.38]. Women who planned their pregnancies were 28% more likely to have an optimal CCI than those who had not planned OR = 1.28 [95% CI;1.05, 1.56]. Finally, women with more than 4 ANC were 2.43 times more likely to have an optimal CCI than those with the least OR = 2.43 [95% CI; 2.03, 2.90]. The spatial analysis reveals significant disparities with an aggregation of high partial CCI in Labé between 2012 and 2018. Conclusion This study showed an increase in CCI between 2012 and 2018. Policies should improve access to care and information for poor women. Besides, strengthening ANC visits and reducing regional inequalities increases optimal CCI.

International audience; In this article, we focus on the design of a second language (L2) formative feedback system that provides linguistic complexity graph reports on the writings of English for special purposes students at the university level. The system is evaluated in light of formative instruction features pointed out in the literature. The significance of complexity metrics is also evaluated. A learner corpus of English classified according to the Common European Framework of References for Languages (CEFR) was processed using a pipeline that computes 83 complexity metrics. By way of analysis of variance (ANOVA) testing, multinomial logistic regression, and clustering methods, we identified and validated a set of nine significant metrics in terms of proficiency levels. Validation with classification gave 67.51% (A level), 60.16% (B level), and 60.47% (C level) balanced accuracy. Clustering showed between 53.10% and 67.37% homogeneity, depending on the level. As a result, these metrics were used to create graphical reports about the linguistic complexity of learner writing. These reports are designed to help language teachers diagnose their students’ writings in comparison with prerecorded cohorts of different proficiencies.

International audience; BACKGROUND: Exceptional episodes of exposure to high levels of persistent organic pollutants have already been associated with developmental defects of enamel among children, but knowledge is still scarce concerning the contribution of background levels of environmental contamination. METHODS: Children of the French PELAGIE mother-child cohort were followed from birth, with collection of medical data and cord blood samples that were used to measure polychlorinated biphenyls (PCBs), organochlorine pesticides (OCs), and perfluorinated alkyl substances (PFASs). At 12 years of age, molar-incisor hypomineralization (MIH) and other enamel defects (EDs) were recorded for 498 children. Associations were studied using logistic regression models adjusted for potential prenatal confounders. RESULTS: An increasing log-concentration of β-HCH was associated with a reduced risk of MIH and EDs (OR = 0.55; 95% CI, 0.32-0.95, and OR = 0.65; 95% CI, 0.43-0.98, respectively). Among girls, intermediate levels of p,p’-DDE were associated with a reduced risk of MIH. Among boys, we observed an increased risk of EDs in association with intermediate levels of PCB 138, PCB 153, PCB 187, and an increased risk of MIH with intermediate levels of PFOA and PFOS. CONCLUSIONS: Two OCs were associated with a reduced risk of dental defects, whereas the associations between PCBs and PFASs and EDs or MIH were generally close to null or sex-specific, with an increased risk of dental defects in boys. These results suggest that POPs could impact amelogenesis. Replication of this study is required and the possible underlying mechanisms need to be explored.

International audience; In France and in other countries, we observed a significant growth in human polyvalent immunoglobulins (PvIg) usage. PvIg is manufactured from plasma collected from numeral donors, and its production is complex. Supply tensions have been observed for several years, and it is necessary to limit their consumption. Therefore, French Health Authority (FHA) provided guidelines in June 2018 to restrict their usage. This research aims to assess the guidelines’ impact of the FHA on the use of PvIg. We analyzed data from Rennes University Hospital, where all PvIg prescriptions are reported electronically with quantity, rhythm, and indication. From the clinical data warehouses of RUH, we extracted comorbidities and lab results to evaluate the more complex guidelines. We globally noticed a reduction in the consumption of PvIg after the guidelines. Compliance with the recommended quantities and rhythms have also been observed. By combining two sources of data, we have been able to show an impact of FHA’s guidelines on the consumption of PvIg.

In recent decades, the detrimental effects of environmental contaminants on human health have become a serious public concern. Organophosphate (OP) pesticides are widely used in agriculture, and the negative impacts of OP and its metabolites on human health have been demonstrated. We hypothesized that exposure to OPs during pregnancy could impose damaging effects on the fetus by affecting various processes. We analyzed sex-specific epigenetic responses in the placenta samples obtained from the mother–child PELAGIE cohort. We assayed the telomere length and mitochondrial copy numbers using genomic DNA. We analyzed H3K4me3 by using chromatin immunoprecipitation followed by qPCR (ChIP‒qPCR) and high-throughput sequencing (ChIP-seq). The human study was confirmed with mouse placenta tissue analysis. Our study revealed a higher susceptibility of male placentas to OP exposure. Specifically, we observed telomere length shortening and an increase in γH2AX levels, a DNA damage marker. We detected lower histone H3K9me3 occupancy at telomeres in diethylphosphate (DE)-exposed male placentas than in nonexposed placentas. We found an increase in H3K4me3 occupancy at the promoters of thyroid hormone receptor alpha (THRA), 8-oxoguanine DNA glycosylase (OGG1) and insulin-like growth factor (IGF2) in DE-exposed female placentas. H3K4me3 occupancy at PPARG was increased in both male and female placentas exposed to dimethylphosphate (DM). The genome-wide sequencing of selected samples revealed sex-specific differences induced by DE exposure. Specifically, we found alterations in H3K4me3 in genes related to the immune system in female placenta samples. In DE-exposed male placentas, a decrease in H3K4me3 occupancy at development-related, collagen and angiogenesis-related genes was observed. Finally, we observed a high number of NANOG and PRDM6 binding sites in regions with altered histone occupancy, suggesting that the effects were possibly mediated via these factors. Our data suggest that in utero exposure to organophosphate metabolites affects normal placental development and could potentially impact late childhood.

International audience; The objectives of environmental health research are diverse (e.g.: identifying situations at potential risk, estimating exposures and effects, testing the effectiveness of preventive actions) and related methods are diverse as well. Opportunities for greater implication of the civil society and related challenges differ at each step of research activities. These aspects need to be better known and shared collectively.

The development of medico-administrative databases over the last few decades has led to an evolution and to a significant production of epidemiological studies on infectious diseases based on retrospective medical data and consumption of care. This new form of epidemiological research faces numerous methodological challenges, among which the assessment of the validity of targeting algorithm. We conducted a scoping review of studies that undertook an estimation of the completeness and validity of French medico-administrative databases for infectious disease epidemiological research. Nineteen validation studies and nine capture-recapture studies were identified. These studies covered 20 infectious diseases and were mostly based on the evaluation of hospital claimed data. The evaluation of their methodological qualities highlighted the difficulties associated with these types of research, particularly those linked to the assessment of their underlying hypotheses. We recall several recommendations relating to the problems addressed, which should contribute to the quality of future evaluation studies based on medico-administrative data and consequently to the quality of the epidemiological indicators produced from these information systems.

Research aim and purposeThe benefits of Electronic Patient -Reported Outcomes (e-PRO) for telemonitoring are well established, allowing early detection of illnesses and continuous monitoring of patients. The primary objective of the PROTECTY study was to assess the compliance with patient use of the telemonitoring platform Cureety. An exploratory objective was to assess if the first-month health status is a prognostic factor of progression free-survival (PFS) and overall survival (OS) for prostate cancer patient.MethodsThis prospective study was conducted at the Military Hospital Bégin on prostate cancer patients. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluates the health status of the patient based on the reported adverse events, with a classification into 2 different states: Good Health Status (GHS) and Poor Health status (PHS).ResultsSixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 74.0 (range 58.0–94.0). 78% presented a metastatic stage, and the most represented cancer was mHSPC. Overall, 2,457 questionnaires were completed by the patients, 4.0% resulted in a health classification in to monitor or critical state. 87% of patients were classified in the GHS group. The compliance was 72% in the overall population during the first month, 71% in GHS group and 75% in PHS group. The median follow-up was 8 months. PFS at 6 months was 84% in GHS group vs. 57% in PHS group, p = 0.19. OS at 6 months was 98% in GHS group vs. 83% in PHS group, p = 0.31.ConclusionsOur study showed that compliance was satisfactory. The feasibility of remote monitoring for prostate cancer patients means that they should benefit from its implementation. Our study is also the first to assess the correlation between treatment tolerance and survival. The initial results suggest that e-PRO assessment could help identify in the early stages the patients that require further health assessment and potential therapeutic changes. While further follow-up of more patients will be required, our study highlights the importance of e-PRO in cancer patient care.

Background Worldwide, a significant proportion of head and neck cancers is attributed to the Human papillomavirus (HPV). It is imperative that we acquire a solid understanding of the natural history of this virus in head and neck squamous cell carcinoma (HNSCC) development. Our objective was to investigate the role of sexual behaviour in the occurrence of HNSCC in the French West Indies. Additionally, we evaluated the association of high risk of HPV (Hr-HPV) with sexual behaviour in risk of cancer. Methods We conducted a population-based case-control study (145 cases and 405 controls). We used logistic regression models to estimate adjusted odds-ratios (OR), and their 95% confidence intervals (CI). Results Compared to persons who never practiced oral sex, those who practiced at least occasionally had a lower HNSCC risk. First sexual intercourse after the age of 18 year was associated with a 50% reduction of HNSCC risk, compared to those who began before 15 years. HNSCC risk was significantly reduced by 60% among persons who used condoms at least occasionally. The associations for ever condom use and oral sex were accentuated following the adjustment for high-risk HPV (Hr-HPV). Oral Hr-HPV was associated with several sexual behaviour variables among HNSCC cases. However, none of these variables were significantly associated with oral HPV infections in the population controls. Conclusion First intercourse after 18 years, short time interval since last intercourse and ever condom use were inversely associated with HNSCC independently of oral Hr-HPV infection. Sources of transmission other than sexual contact and the interaction between HPV and HIV could also play a role in HNSCC etiology.

International audience

International audience

International audience; Selective serotonin reuptake inhibitors (SSRIs) are the most popular antidepressant medications used to manage perinatal mood disturbances, yet our understanding of how they affect the microbiome-gut-brain axis of the mother and offspring is limited. The purpose of this study was to determine how peripartum SSRI treatment may prevent the effects of gestational stress on plasticity in the maternal hippocampus, plasticity in the neonatal brain and related changes in gut microbiota. To do this Sprague-Dawley female rats were left untreated or subjected to unpredictable stress during pregnancy. Half of the females were supplemented daily with fluoxetine. On postpartum day 2 brains were collected for measurement of plasticity (neurogenesis and microglia content) in the maternal hippocampus and in the neonatal brain. Glucocorticoid receptor density was also investigated in the maternal hippocampus. Microbiota composition was analyzed in fecal samples of dams during and after pregnancy, and colon tissue samples from offspring on postnatal day 2. Main findings show there are significant changes to the maternal microbiome-gut-brain axis that may be fundamental to mediating plasticity in the maternal hippocampus. In addition, there is significant impact of gestational stress on neonatal gut microbiota and brain microglia density, while the effects of SSRIs are limited. This is the first study to explore the impact of gestational stress and SSRIs on the microbiome-gut-brain axis in the mother and neonate. Findings from this study will help inform pathways to intervention strategies including stress reduction techniques and/or microbiota targeted nutritional approaches directed towards improving maternal gut health and outcomes for mother and neonate.