Early incidence of occupational asthma among young bakers, pastry-makers and hairdressers: design of a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Occupational exposures are thought to be responsible for 10-15% of new-onset asthma cases in adults, with disparities across sectors. Because most of the data are derived from registries and cross-sectional studies, little is known about incidence of occupational asthma (OA) during the first years after inception of exposure. This paper describes the design of a study that focuses on this early asthma onset period among young workers in the bakery, pastry making and hairdressing sectors in order to assess early incidence of OA in these "at risk" occupations according to exposure duration, and to identify risk factors of OA incidence.</p> <p>Methods/Design</p> <p>The study population is composed of subjects who graduated between 2001 and 2006 in these sectors where they experience exposure to organic or inorganic allergenic or irritant compounds (with an objective of 150 subjects by year) and 250 young workers with no specific occupational exposure. A phone interview focusing on respiratory and 'Ear-Nose-Throat' (ENT) work-related symptoms screen subjects considered as "possibly OA cases". Subjects are invited to participate in a medical visit to complete clinical and lung function investigations, including fractional exhaled nitric oxide (FE_NO) and carbon monoxide (CO) measurements, and to collect blood samples for IgE (Immunoglobulin E) measurements (total IgE and IgE for work-related and common allergens). Markers of oxidative stress and genetic polymorphisms exploration are also assessed. A random sample of 200 "non-cases" (controls) is also visited, following a nested case-control design.</p> <p>Discussion</p> <p>This study may allow to describ a latent period between inception of exposure and the rise of the prevalence of asthma symptoms, an information that would be useful for the prevention of OA. Such a time frame would be suited for conducting screening campaigns of this emergent asthma at a stage when occupational hygiene measures and adapted therapeutic interventions might be effective.</p> <p>Trial registration</p> <p>Clinical trial registration number is NCT01096537.</p

A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far

IgE-mediated anaphylactic reaction against free synthetic folic acid and methyl folate

International audienceWe report 2 cases with immediate-type reactions to synthetic folic acid and methylfolate tablets and folic acid-fortified cereals and identification of specific IgE against free folic acid. Folic acid sensitization should be carefully considered in patients taking supplements and enriched food products and in those with suspected cereal allergy

Le dépistage de la phénylcétonurie en France

International audiencePhenylketonuria is the most common inborn error of metabolism and causes irreversible mental retardation if left untreated. Its newborn screening was made possible by the technique of blood collection on filter paper developed by Robert Guthrie. Neonatal PKU screening began in France in the early 1970s. It was initially carried out by a bacteriological method, then by fluorometry, and finally, since 2020, by tandem mass spectrometry. More than 35 million newborns have been screened to date. This resulted in the diagnosis of more than 3,500 children with PKU or mild hyperphenylalaninemia. The management of these children has improved over time, in particular thanks to the techniques of biochemistry and molecular genetics which lead to an accurate diagnosis and the arrival of drug treatment by sapropterin. Thanks to this screening, which allows for early management, the prognosis of PKU has been transformed and, although neurological or behavioral problems may arise, these patients are living normally today.La phénylcétonurie (PCU) est la plus fréquente des erreurs innées du métabolisme et entraîne un retard mental irréversible en l’absence de traitement. Son dépistage néonatal a été rendu possible grâce à la technique de recueil de sang sur papier buvard mise au point par Robert Guthrie. Le dépistage néonatal de la PCU a débuté en France au début des années 1970. Il a été initialement réalisé par une technique bactériologique, puis fluorimétrique et, enfin, depuis 2020 par spectrométrie de masse en tandem. Plus de 35 millions de nouveau-nés ont été dépistés à ce jour, ce qui a permis de diagnostiquer plus de 3 500 enfants porteurs de PCU ou hyperphénylalaninémie modérée. La prise en charge de ces enfants a évolué avec le temps, en particulier grâce aux techniques de biochimie et de génétique moléculaire qui permettent un diagnostic précis et grâce à l’arrivée d’un traitement médicamenteux par saproptérine. Grâce à ce dépistage, qui permet une prise en charge précoce, le pronostic de la PCU a été transformé et, même s’il peut survenir des problèmes neurologiques ou comportementaux, ces patients ont une vie normale aujourd’hui

Blood myeloperoxidase‐DNA, a biomarker of early response to SARS‐CoV‐2 infection?

International audienceConvergent arguments suggest that innate immunity related to neutrophils, and in particular neutrophil extracellular traps (NETs), could play a key role in response to SARS-CoV-2 infection

Hypozincemia in the early stage of COVID-19 is associated with an increased risk of severe COVID-19

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Sirt1-PPARS Cross-Talk in Complex Metabolic Diseases and Inherited Disorders of the One Carbon Metabolism

International audienceSirtuin1 (Sirt1) has a NAD (+) binding domain and modulates the acetylation status of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and Fork Head Box O1 transcription factor (Foxo1) according to the nutritional status. Sirt1 is decreased in obese patients and increased in weight loss. Its decreased expression explains part of the pathomechanisms of the metabolic syndrome, diabetes mellitus type 2 (DT2), cardiovascular diseases and nonalcoholic liver disease. Sirt1 plays an important role in the differentiation of adipocytes and in insulin signaling regulated by Foxo1 and phosphatidylinositol 3'-kinase (PI3K) signaling. Its overexpression attenuates inflammation and macrophage infiltration induced by a high fat diet. Its decreased expression plays a prominent role in the heart, liver and brain of rat as manifestations of fetal programming produced by deficit in vitamin B12 and folate during pregnancy and lactation through imbalanced methylation/acetylation of PGC1α and altered expression and methylation of nuclear receptors. The decreased expression of Sirt1 produced by impaired cellular availability of vitamin B12 results from endoplasmic reticulum stress through subcellular mislocalization of ELAVL1/HuR protein that shuttles Sirt1 mRNA between the nucleus and cytoplasm. Preclinical and clinical studies of Sirt1 agonists have produced contrasted results in the treatment of the metabolic syndrome. A preclinical study has produced promising results in the treatment of inherited disorders of vitamin B12 metabolism

Mechanisms of homocysteine-induced damage to the endothelial, medial and adventitial layers of the arterial wall

International audienceHomocysteine (Hcy) is a non-protein forming amino acid which is the direct metabolic precursor of methionine. Increased concentration of serum Hcy is considered a risk factor for cardiovascular disease and is specifically linked to various diseases of the vasculature. Serum Hcy is associated with atherosclerosis, hypertension and aneurysms of the aorta in humans, though the precise mechanisms by which Hcy contributes to these conditions remain elusive. Results from clinical trials that successfully lowered serum Hcy without reducing features of vascular disease in cardiovascular patients have cast doubt on whether or not Hcy directly impacts the vasculature. However, studies in animals and in cell culture suggest that Hcy has a vast array of toxic effects on the vasculature, with demonstrated roles in endothelial dysfunction, medial remodeling and adventitial inflammation. It is hypothesized that rather than serum Hcy, tissue-bound Hcy and the incorporation of Hcy into proteins could underlie the toxic effects of Hcy on the vasculature. In this review, we present evidence for Hcy-associated vascular disease in humans, and we critically examine the possible mechanisms by which Hcy specifically impacts the endothelial, medial and adventitial layers of the arterial wall. Deciphering the mechanisms by which Hcy interacts with proteins in the arterial wall will allow for a better understanding of the pathomechanisms of hyperhomocysteinemia and will help to define a better means of prevention at the appropriate window of life

DataSheet_1_A systematic review and meta-analysis of proteomic and metabolomic alterations in anaphylaxis reactions.xlsx

BackgroundAnaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the release of mediators. However, the well-known underlying pathological mechanisms do not fully explain the whole variety of clinical and immunological presentations. We performed a systemic review of proteomic and metabolomic studies and analyzed the extracted data to improve our understanding and identify potential new biomarkers of anaphylaxis.MethodsProteomic and metabolomic studies in both human subjects and experimental models were extracted and selected through a systematic search conducted on databases such as PubMed, Scopus, and Web of Science, up to May 2023.ResultsOf 137 retrieved publications, we considered 12 for further analysis, including seven on proteome analysis and five on metabolome analysis. A meta-analysis of the four human studies identified 118 proteins with varying expression levels in at least two studies. Beside established pathways of mast cells and basophil activation, functional analysis of proteomic data revealed a significant enrichment of biological processes related to neutrophil activation and platelet degranulation and metabolic pathways of arachidonic acid and icosatetraenoic acid. The pathway analysis highlighted also the involvement of neutrophil degranulation, and platelet activation. Metabolome analysis across different models showed 13 common metabolites, including arachidonic acid, tryptophan and lysoPC(18:0) lysophosphatidylcholines.ConclusionOur review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions. These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024506246.</p