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Analyzing the impact of phthalate and DINCH exposure on fetal growth in a cohort with repeated urine collection
No full textInternational audienceBackground: Most previous studies investigating the associations between prenatal exposure to phthalates and fetal growth relied on measurements of phthalate metabolites at a single time point. They also focused on weight at birth without assessing growth over pregnancy, preventing the identification of potential periods of fetal vulnerability. We examined the associations between pregnancy urinary phthalate metabolites and fetal growth outcomes measured twice during pregnancy and at birth.Methods: For 484 pregnant women, we assessed 13 phthalate and two 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) metabolite concentrations from two within-subject weekly pools of up to 21 urine samples (median of 18 and 34 gestational weeks, respectively). Fetal biparietal diameter, femur length, head and abdominal circumferences were measured during two routine pregnancy follow-up ultrasonographies (median 22 and 32 gestational weeks, respectively) and estimated fetal weight (EFW) was calculated. Newborn weight, length, and head circumference were measured at birth. Associations between phthalate/DINCH metabolite and growth parameters were investigated using adjusted linear regression and Bayesian kernel machine regression models.Results: Detection rates were above 99 % for all phthalate/DINCH metabolites. While no association was observed with birth measurements, mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were positively associated with most fetal growth parameters measured at the second trimester. Specifically, MiBP was positively associated with biparietal diameter, head and abdominal circumferences, while MnBP was positively associated with EFW, head and abdominal circumferences, with stronger associations among males. Pregnancy MnBP was positively associated with biparietal diameter and femur length at third trimester. Mixture of phthalate/DINCH metabolites was positively associated with EFW at second trimester.Conclusions: In this pregnancy cohort using repeated urine samples to assess exposure, MiBP and MnBP were associated with increased fetal growth parameters. Further investigation on the effects of phthalates on child health would be relevant for expanding current knowledge on their long-term effects
Intrafamilial associations of sleep multitrajectory groups between ages of 3 and 60 months in the SEPAGES cohort
No full textInternational audienceObjectives. We investigated intra-familial sleep evolution by identifying children’s sleep multi-trajectory groups (SMTGs) between 3- and 60-months of age and their association with parental SMTGs.Methods. We included 180 children from the SEPAGES cohort (Grenoble, France) whose parents belonged to previously identified SMTGs, through group-based multi-trajectory modelling (GBMTM), between 3 and 36 months postpartum, using nighttime (NSD) and weekend daytime (DSD) sleep durations and subjective sleep loss (SSL), comprising “No”, “Subjective” and “Global” sleep problems groups. Child sleep information (NSD, DSD, SSL, night waking (NW) and sleep onset difficulties (SOD)) was collected by parental questionnaires at 3-, 12-, 36- and 60-months. We identified SMTGs using GBMTM in children and examined their associations with parental SMTGs using multinomial logistic regressions.Results. We identified three SMTGs in children: the “No/few” group (29.4%) had moderate NSD, long DSD, low SSL/NW/SOD prevalence, the “Moderate” group (60.0%) had long NSD and moderate DSD, and medium SSL/NW/SOD prevalence, and the “Global” group (10.6%) had the shortest NSD and DSD, and the highest SSL/NW/SOD prevalence. After adjusting for covariates, mothers in the “Global” group were more likely to have children in the same group, and mothers in “Subjective” and “Global” groups were less likely to have children in the “Moderate” group than in the “No/few” group. No association was identified with paternal or couple SMTGs.Conclusions. The observed associations between parent-child SMTGs suggest greater maternal sensitivity to or involvement in the child’s sleep than the fathers. Early preventive sleep actions could improve sleep in children and mothers
Les déformations des diatomées pour évaluer les effets d’une contamination complexe : le cas de la Cleurie.
No full textNational audienceLes diatomées sont couramment utilisées pour évaluer la qualité de l’eau. Outre les indicateurs basés sur la diversité des espèces présentes, la manière dont les contaminants agissent sur la variabilité morphologique au sein d’une même espèce peuvent également fournir des informations utiles. Ainsi, l’apparition de déformations est communément admise comme un indicateur de stress. Toutefois, ces déformations peuvent être difficiles à identifier et à dénombrer, et il est également délicat d'en qualifier l'intensité. Au-delà des déformations, d’autres changements plus subtils, non tératologiques, pourraient s’avérer utiles à quantifier en routine.La Cleurie est un petit cours d’eau vosgien de tête de bassin versant forestier, qui est soumis depuis de nombreuses années à des rejets industriels issus de blanchisserie. Un suivi temporel (37 prélèvements) a été réalisé en 2019 sur différentes stations du cours d’eau. Il a permis de révéler la présence de diatomées déformées avec des valeurs d’abondance relative largement supérieures (jusqu’à 8%) par rapport à une situation considérée comme normale (<0.5%). D’autre part, la présence de ces formes anormales a varié en fonction de la distance aux rejets : une diminution en aval de la zone d’étude a été observée, avec des valeurs d’abondance restant toutefois relativement élevées au cours de l’année (proche de 1%).Cette première étape d’analyse nous a permis d’identifier un taxon suffisamment abondant dans nos échantillons et fréquemment sujet à déformation, afin d’initier une approche de morphométrie quantitative : Fragilaria pectinalis (O.F.Müller) Lyngbye s.l (FPEC). Près de 2000 images individuelles de FPEC ont ainsi été obtenues, à partir desquelles un grand nombre de descripteurs morphologiques standardisés (43 au total) ont été calculés. Une douzaine de ces descripteurs ont finalement été suffisants pour décrire la plus grande partie de la variabilité morphologique observée au sein de ce taxon. Aucun des descripteurs considéré isolément des autres n’a pu être relié directement à la qualité chimique du cours d’eau. Mais la combinaison d’un nombre limité d’entre eux (en particulier ellipticité et concavité) a permis de distinguer les individus les plus déformées par rapport à des images de diatomées saines ou déformées de manière moins évidente. Un indice multi-descripteur pourrait donc être développé sur cette base. Cette approche est donc prometteuse dans la mesure où la quantification de ces descripteurs est plus robuste (moins biaisée car plus objective) que l’approche manuelle habituellement mise en œuvre par les opérateurs et surtout entièrement automatisable
Investigation of genotoxicity induced by intermediate frequency magnetic field combined with ionizing radiation: In vitro study on human fibroblast cells
No full textInternational audienceThese days, exposure to electromagnetic fields has become omnipresent in modern society. Not only the extremely-low frequency and radiofrequency, but also intermediate frequency (IF) magnetic field (MF) might be absorbed in the human body resulting in an ever-growing concern about their possible health effects. Devices, such as induction cooktops, chargers, compact fluorescent lamps, touchscreens and electric vehicles emit a wide range of intermediate frequency fields. We investigated the effects of 22 kHz or 250 kHz intermediate frequency magnetic field exposure on the human skin cells. We also examined the adaptive response phenomenon; whether IF MF exposure could possibly reduce the harmful genotoxic effects of ionizing radiation. To get answers to these questions, in vitro studies were carried out on fibroblast cells to investigate the effects on oxidative stress, DNA damage and micronucleus formation. We found a decreased micronucleus formation due to the 22 kHz IF MF exposure and significantly increased oxidative stress in fibroblast cells, which were exposed only to 250 kHz IF MF. We were unable to detect the protective or co-genotoxic effects of intermediate frequency magnetic field exposure combined with ionizing radiation, thus we found no evidence for the adaptive response phenomena
Les reconnaissances en maladie professionnelle lors du suivi de la cohorte ARDCO
No full textInternational audienceIntroduction: Questions concerning under-reporting of occupational diseases (OD) linked to asbestos exposure are regularly voiced in France. Monitoring of the French multicenter Asbestos-Related Disease Cohort (ARDCO), which ensures post-occupational medical surveillance of subjects having been exposed to asbestos, provides information on (1) the medico-legal steps taken following screening by computed tomography (CT) for benign thoracic diseases, and (2) recognition of OD as a causal factor in malignant diseases.Methods: OD recognition - and possible compensation - was analyzed in July 2021 among 13,289 volunteers in the cohort recruited between 2003 and 2005.Results: Fifteen percent of the subjects in the cohort were found to have at least one recognized asbestos-related OD (78.2% benign pleural disease, 10.3% asbestosis, 14.2% lung cancer, and 6.0% mesothelioma). Only 58% of pleural plaques reported by the radiologist who performed the CT resulted in their recognition as ODs. On a parallel track, 88.7% of the mesotheliomas identified based on French National health insurance data and 46.9% of lung cancers were recognized as ODs.Conclusions: This study confirms the feasibility of a system designed to facilitate recognition, leading to possible compensation, of asbestos-related occupational diseases. The system could be improved by better training of the medical actors involved
Extensive HPLC tandem mass spectrometry characterization of soluble degradation products of biodegradable nanoplastics under environmentally relevant temperature and irradiation conditions
No full textInternational audiencePolyester-based plastics, and in particular biodegradable ones, are increasingly used becausethey may be a partial solution to environmental pollution issues. Therefore, properidentification of their degradation products is strongly needed. In the present work, weoptimised a method to investigate the degradation of two biodegradable polymers, polylacticacid (PLA) and polycaprolactone (PCL), together with the non-biodegradable polyethyleneterephthalate (PET). We focused the work on nanosize particles (150-200 nm), in relationshipwith the concern about the presence of nano- and micro-plastics in the environment. We aimedat characterizing the low molecular weight degradation products, which are likely to diffuse andinteract with living cells. For this purpose, the polymer samples were aged at 40 or 55°C undersimulated sunlight in a climatic chamber, i.e. in highly controlled conditions, and the resultingliquid phase was analyzed by liquid chromatography coupled to tandem mass spectrometry. Thelatter technique was used in four different detection modes: single stage mass spectrometry,product ion scan, precursor ion scan and neutral loss. While the first technique has been appliedin other works, the unique combination of all these analytical strategies allowed us to show thathydrolysis was the overwhelming degradation pathway for PLA, PCL and even PET. Oligomersranging between 1 and 8 monomers were identified for PLA and 2 and 8 for PCL. Shortercompounds composed of 1 to 4 units were detected in PET samples. Altogether, the presentwork reports novel information on the degradation of nanosize plastics and proposes a robustanalytical strategy for the extensive characterization of soluble degradation products of plasticmaterial
Dietary intakes of dioxins and polychlorobiphenyls (PCBs) and mortality: EPIC cohort study in 9 European countries
No full textInternational audienceDioxins and polychlorinated biphenyls (PCBs) are toxic, endocrine disruptors and persistent chemicals for which the main exposure source is diet due to their bioaccumulation and biomagnification in food chains. Cohort studies in the general populations have reported inconsistent associations between these chemicals in serum/plasma and mortality. Our objective was to study the association between dietary intake of 17 dioxins and 35 PCBs and all-cause, cancer-specific and cardiovascular-specific mortalities were assessed in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with European food contamination data provided by the European Food Safety Authority. We applied multivariable Cox regressions. The analysis included 451,390 adults (mean ± SD age:51.1 ± 9.7 years) with 46,627 deaths and a median follow-up of 17.4 years (IQR = 15.2u201319.1). A U-shaped non-linear association with all-cause mortality for dietary intake of dioxins (Pnon-linearity<0.0001), DL-PCB (Pnon-linearity = 0.0001), and NDL-PCBs (Pnon-linearity<0.01) was observed. For example, the hazard ratios (95%Confidance interval) for all-cause mortality obtained with the spline model was equal to 1.03 (1.02u20131.05) for low levels of intake to dioxins (7 pg TEQ/day), 0.93 (0.90u20130.96) for moderate levels of intake (25 pg TEQ/day), while for high levels of intake (55 pg TEQ/day) it was 1.03 (0.97u20131.09). Intake of dioxins, DL-PCBs and NDL-PCBs was not associated with cardiovascular mortality. There was no association between intakes of dioxins and cancer mortality, but a U-shaped association was observed for intake of DL-PCBs and intakes of NDL-PCBs and cancer mortality. The PCBs and dioxins are known to have endocrine disrupting properties which can lead to non-monotonic dose responses. These results need to be interpreted with caution and further studies are needed to better clarify the association between dietary intake of dioxins and PCB and mortality in the general population
Effects of different amosite preparations on macrophages, lung damages, and autoimmunity
No full textInternational audienceThe underlying mechanisms of asbestos-related autoimmunity are poorly understood. As the size, surface reactivity, and free radical activity of asbestos particles are considered crucial regarding the health effects, this study aims to compare the effects of exposure to pristine amosite (pAmo) or milled amosite (mAmo) particles on lung damage, autoimmunity, and macrophage phenotype. Four months after lung exposure to 0.1 mg of amosite, BAL levels of lactate dehydrogenase, protein, free DNA, CCL2, TGF-β1, TIMP-1, and immunoglobulin A of pAmo-exposed C57Bl/6 mice were increased when compared to fluids from control- and mAmo-exposed mice. Effects in pAmo-exposed mice were associated with lung fibrosis and autoimmunity including anti-double-strand DNA autoantibody production. mAmo or pAmo at 20 µg/cm(2) induced a pro-inflammatory phenotype characterized by a significant increase in TNFα and IL-6 secretion on human monocyte-derived macrophages (MDMs). mAmo and pAmo exposure induced a decrease in the efferocytosis capacities of MDMs, whereas macrophage abilities to phagocyte fluorescent beads were unchanged when compared to control MDMs. mAmo induced IL-6 secretion and reduced the percentage of MDMs expressing MHCII and CD86 markers involved in antigen and T-lymphocyte stimulation. By contrast, pAmo but not mAmo activated the NLRP3 inflammasome, as evaluated through quantification of caspase-1 activity and IL-1β secretion. Our results demonstrated that long-term exposure to pAmo may induce significant lung damage and autoimmune effects, probably through an alteration of macrophage phenotype, supporting in vivo the higher toxicity of entire amosite (pAmo) with respect to grinded amosite. However, considering their impact on efferocytosis and co-stimulation markers, mAmo effects should not be neglected. KEY MESSAGES: Lung fibrosis and autoimmunity induced by amosite particles depend on their physicochemical characteristics (size and surface) Inhalation exposure of mice to pristine amosite fibers is associated with lung fibrosis and autoimmunity Anti-dsDNA antibody is a marker of autoimmunity in mice exposed to pristine amosite fibers Activation of lung mucosa-associated lymphoid tissue, characterized by IgA production, after exposure to pristine amosite fibers Pristine and milled amosite particle exposure reduced the efferocytosis capacity of human-derived macrophages
L’exposition chronique à de faibles doses de pesticides via l’alimentation: Impact d’une exposition chronique à un mélange de faibles doses de pesticides sur l’apparition de la maladie de Parkinson et du diabète de type 2 dans des modèles murins transgéniques, et étude des liens entre ces deux pathologies
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Pharmacology and molecular modeling studies of sulfoxaflor, flupyradifurone and neonicotinoids on the human neuronal α7 nicotinic acetylcholine receptor
No full textInternational audienceWe conducted electrophysiological and molecular docking studies using a heterologous expression system (Xenopus oocytes) to compare the effects of four neonicotinoids (acetamiprid, imidacloprid, clothianidin and thiamethoxam), one sulfoximine, (sulfoxaflor), and one butenolide (flupyradifurone), on human α7 neuronal nicotinic acetylcholine receptors (nAChRs). All neonicotinoids (except thiamethoxam), as well as the recently introduced nAChR competitive modulators, flupyradifurone and sulfoxaflor, appear to be weaker agonists than acetylcholine. Two mutations in loop C (E211N and E211P) and one mutation in loop D (Q79K), known to be involved in the binding properties of neonicotinoids were introduced to the α7 wild type. Interestingly, the acetylcholine and nicotine-evoked activation was not modified in human α7 mutated receptors, but the net charge was enhanced for clothianidin and imidacloprid, respectively. Flupyradifurone responses strongly increased under the Q79K mutation. The molecular docking investigations demonstrated that the orientations and interactions of the ligands considered were in accordance with those observed experimentally. Specifically, the charged fragments of acetylcholine and nicotine, used as reference ligands, and their neonicotinoid homologs were found to be surrounded by aromatic residues, with key interactions with Trp171 and Y210. Furthermore, the molecular docking investigations predicted the water-mediated interaction between the carbonyl oxygen of acetylcholine and the Nsp 2 nitrogen of the pyridine ring for nicotine (as well as for the majority of the corresponding neonicotinoid fragments) and main chain NH of L141. The docking scores, extending over a significant range of 6 kcal/mol, showed that most neonicotinoids were poorly stabilized in the α7 nAChR compared to acetylcholine, except sulfoxaflor.</div