Early Effect Markers and Exposure Determinants of Metalworking Fluids Among Metal Industry Workers: Protocol for a Field Study.

Exposure to aerosols from metalworking fluids (MWF) has previously been related to a series of adverse health outcomes (eg, cancer, respiratory diseases). Our present epidemiological study focuses on occupational exposures to MWF and a panel of exposure and effect biomarkers. We hypothesize that these health outcomes are caused by particle exposure that generates oxidative stress, leading to airway inflammation and ultimately to chronic respiratory diseases. We aimed to assess whether MWF exposure, in particular as characterized by its oxidative potential, is associated with biomarkers of oxidative stress and inflammation as well as genotoxic effects. The ultimate goal is to develop exposure reduction strategies based on exposure determinants that best predict MWF-related health outcomes. The following relationships will be explored: (1) exposure determinants and measured exposure; (2) occupational exposure and preclinical and clinical effect markers; (3) exposure biomarkers and biomarkers of effect in both exhaled breath condensate and urine; and (4) biomarkers of effect, genotoxic effects and respiratory symptoms. At least 90 workers from France and Switzerland (30 controls, 30 exposed to straight MWF and 30 to aqueous MWF) were followed over three consecutive days after a nonexposed period of at least two days. The exposure assessment is based on MWF, metal, aldehyde, and ultrafine particle number concentrations, as well as the intrinsic oxidative potential of aerosols. Furthermore, exposure biomarkers such as metals, metabolites of polycyclic aromatic hydrocarbons and nitrosamine are measured in exhaled breath condensate and urine. Oxidative stress biomarkers (malondialdehyde, 8-isoprostane, 8-hydroxy-2'-deoxyguanosine, nitrates, and nitrites) and exhaled nitric oxide, an airway inflammation marker, are repeatedly measured in exhaled breath condensate and urine. Genotoxic effects are assessed using the buccal micronucleus cytome assay. The statistical analyses will include modelling exposure as a function of exposure determinants, modelling the evolution of the biomarkers of exposure and effect as a function of the measured exposure, and modelling respiratory symptoms and genotoxic effects as a function of the assessed long-term exposure. Data collection, which occurred from January 2018 until June 2019, included 20 companies. At the date of writing, the study included 100 subjects and 29 nonoccupationally exposed controls. This study is unique as it comprises human biological samples, questionnaires, and MWF exposure measurement. The biomarkers collected in our study are all noninvasive and are useful in monitoring MWF exposed workers. The aim is to develop preventative strategies based on exposure determinants related to health outcomes. DERR1-10.2196/13744

Does exposure to inflammatory particles modify the pattern of anion in exhaled breath condensate?

Exposure to environmental and occupational particulate matter (PM) induces health effects on the cardio-pulmonary system. In addition, associations between exposure to PM and metabolic syndromes like diabetes mellitus or obesity are now emerging in the literature. Collection of exhaled breath condensate (EBC) is an appealing non-invasive technique to sample pulmonary fluids. This hypothesis-generating study aims to (1) validate an ion chromatography method allowing the robust determination of different metabolism-related molecules (lactate, formate, acetate, propionate, butyrate, pyruvate, nitrite, nitrate) in EBC; (2) apply this method to EBC samples collected from workers exposed to quartz (a known inflammatory particle), to soapstone (a less inflammatory particle than quartz), as well as to controls. A multi-compound standard solution was used to determine the linearity range, detection limit, repeatability and bias from spiked EBC. The biological samples were injected without further treatment into an ion chromatograph with a conductivity detector. RTube <sup>®</sup> were used for field collection of EBC from 11 controls, 55 workers exposed to soapstone and 12 volunteers exposed to quartz dust. The analytical method used proved to be adequate for quantifying eight anions in EBC samples. Its sub-micromolar detection limits and repeatability, combined with a very simple sample preparation, allowed an easy and fast quantification of different glycolysis or nitrosative stress metabolites. Using multivariate discriminant analysis to maximize differences between groups, we observed a different pattern of anions with a higher formate/acetate ratio in the EBC samples for quartz exposed workers compared to the two other groups. We hypothesize that a modification of the metabolic signature could be induced by exposure to inflammatory particles like quartz and might be observed in the EBC via a change in the formate/acetate ratio

Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients

International audienceAlthough whole-exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called "medical exome" (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non-syndromic intellectual disability (NSID, n = 33), syndromic ID (NSID = 122), pediatric neurodegenerative disorders (n = 7) and autism spectrum disorder (ASD, n = 54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool

Interpersonal Synchronization, Motor Coordination, and Control Are Impaired During a Dynamic Imitation Task in Children With Autism Spectrum Disorder

International audienc

Biomarkers of respiratory allergy in laboratory animal care workers: an observational study

Objectives: Laboratory animal allergy is a highly prevalent occupational disease among exposed workers. The aim of the study was to validate the biomarkers of airway inflammation in laboratory animal (LA) care workers. Methods: All of the participants in this observational study (63 LA care workers and 64 controls) were administered a clinical questionnaire, underwent spirometry and a skin prick or radioallergosorbent test for common and occupational aeroallergens, and the fraction of exhaled nitric oxide (FeNO50), exhaled breath condensate hydrogen peroxide (EBC H2O2) and serum pneumoprotein levels were measured. Multivariate analysis (ANCOVA) was used to assess the interactions of the variables. Results: FeNO50levels correlated with exposure (p = 0.002), sensitisation (p = 0.000) and age (p = 0.001), but there was no interaction between exposure and sensitisation when age was considered in the model (p = 0.146). EBC-H2O2levels were higher in the sensitised workers than in the sensitised controls [0.14 (0.08–0.29) µM vs 0.07 (0.05–0.12) µM; p < 0.05]. Serum surfactant protein A (SP-A) levels were unaffected by exposure, sensitisation or age, although higher levels were observed in symptomatic workers; however, SP-D levels were influenced by exposure (p = 0.024) and age (p = 0.022), and club cell 16 levels were influenced by sensitisation (p = 0.027) and age (p = 0.019). Conclusions: The presence of the clinical symptoms associated with LA exposure and high FeNO levels should prompt further medical assessments in LA workers. Although EBC-H2O2levels do not seem to reflect eosinophilic inflammation, serum SP-A levels could be used to monitor progression from rhinitis to asthma