70 research outputs found
Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth
Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth
Prenatal urban environment and blood pressure trajectories from childhood to early adulthood
Background: Prenatal urban environmental exposures have been associated with blood pressure in children. The dynamic of these associations across childhood and later ages is unknown. Objectives: The purpose of this study was to assess associations of prenatal urban environmental exposures with blood pressure trajectories from childhood to early adulthood. Methods: Repeated measures of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were collected in up to 7,454 participants from a UK birth cohort. Prenatal urban exposures (n = 43) covered measures of noise, air pollution, built environment, natural spaces, traffic, meteorology, and food environment. An exposome-wide association study approach was used. Linear spline mixed-effects models were used to model associations of each exposure with trajectories of blood pressure. Replication was sought in 4 independent European cohorts (up to 9,261). Results: In discovery analyses, higher humidity was associated with a faster increase (mean yearly change in SBP for an interquartile range increase in humidity: 0.29 mm Hg/y, 95% CI: 0.20-0.39) and higher temperature with a slower increase (mean yearly change in SBP per interquartile range increase in temperature: â0.17 mm Hg/y, 95% CI: â0.28 to â0.07) in SBP in childhood. Higher levels of humidity and air pollution were associated with faster increase in DBP in childhood and slower increase in adolescence. There was little evidence of an association of other exposures with change in SBP or DBP. Results for humidity and temperature, but not for air pollution, were replicated in other cohorts. Conclusions: Replicated findings suggest that higher prenatal humidity and temperature could modulate blood pressure changes across childhood.</p
The use of viscoelastic haemostatic assays in the management of major bleeding: A British Society for Haematology Guideline.
BSH paid the expenses incurred during the writing of this guidance
Mononeuritis multiplex following immune checkpoint inhibitors in malignant pleural mesothelioma
IntroductionMononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors.MethodsCase series of three patients with mononeuritis multiplexâall with mesotheliomaâidentified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015âOctober 2022) set up to collect and investigate n-irAEs on a nationwide level.ResultsThree patients (male; median age 86âyears; range 72â88âyears) had pleural mesothelioma and received 10, 4, and 6âcycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3âmonths after rituximab and cyclophosphamide administration.DiscussionWe report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event
Structure analysis of the physiological or pathological clot
Physiologiquement, le caillot sanguin a pour fonction lâarrĂȘt dâun saignement consĂ©cutif Ă une brĂšche vasculaire. Dans un premier temps, ce sont les plaquettes sanguines qui stoppent lâĂ©panchement sanguin, rapidement soutenues par la formation dâun rĂ©seau de fibres de fibrine qui consolide et confĂšre au caillot les propriĂ©tĂ©s nĂ©cessaires pour rĂ©sister Ă la pression sanguine et Ă la fibrinolyse. Le fibrinogĂšne est lâĂ©lĂ©ment de base du rĂ©seau de fibrine. Lors dâune brĂšche vasculaire, la libĂ©ration de facteur tissulaire entraine le dĂ©clenchement de la cascade de coagulation qui aboutit Ă la transformation du fibrinogĂšne en monomĂšres de fibrine par lâaction de la thrombine. Ceux-ci sâagrĂšgent longitudinalement pour former des protofibrilles, puis latĂ©ralement pour former un rĂ©seau de fibres de fibrine.A ce jour, de nombreuses Ă©tapes de formation du caillot ont Ă©tĂ© dĂ©crites en dĂ©tail dans la littĂ©rature, cependant les mĂ©canismes et les forces motrices de lâagrĂ©gation latĂ©rale des protofibrilles sont encore mal compris.Lors de ce travail, nous avons Ă©tudiĂ© diffĂ©rents profils de coagulation : de lâhypo-coagulant Ă lâhypercoagulant, en passant par le profil normal et en utilisant un panel variĂ© de techniques : gĂ©nĂ©ration de thrombine, gĂ©nĂ©ration de plasmine, Fibrinographie, Fibrinographie en mode « fibrinolyse », microscopie confocale, thromboĂ©lastomĂ©trie et diffraction des rayons X aux petits angles.Nous avons mis en Ă©vidence la relation entre la quantitĂ© de thrombine prĂ©sente lors de la formation dâun caillot et la structure de celui-ci. En effet, Plus il y a de thrombine, plus le nombre de protofibrilles par fibre est faible et plus le nombre de fibres est important. De plus, nous avons corrĂ©lĂ© le temps dâinitiation de lâagrĂ©gation latĂ©rale des fibres en Fibrinographie avec lâinitiation de la gĂ©nĂ©ration de plasmine. Nous avons ainsi mis en Ă©vidence la production dâune structure du caillot de fibrine anormale en prĂ©sence de dabigatran, grĂące Ă lâutilisation combinĂ©e de la microscopie confocale et de la Fibrinographie.Cette analyse multimodale de la structure du caillot dans diffĂ©rentes conditions apporte des informations supplĂ©mentaires Ă la communautĂ© scientifique, pour permettre de mieux comprendre les mĂ©canismes de formation des caillots de fibrine.Physiologically, the blood function of the clot is to stop bleeding following a vascular breach. Initially, platelets stop blood flow, quickly supported by the formation of a fibrin fibers network that strengthens and gives properties to resist the blood pressure and fibrinolysis. Fibrinogen is the basic element of the fibrin network. During a vascular breach, the release of tissue factor triggers the coagulation cascade that results in the conversion of fibrinogen to fibrin monomers by the action of thrombin. These aggregate longitudinally to form protofibrils, then laterally to form a network of fibrin fibers.To date, many stages of the clot formation have been described in detail in the literature, however the mechanisms and driving forces of the lateral aggregation of protofibrils are still poorly understood.During this work, we studied different coagulation profiles: from hypo-coagulant to hyper-coagulant, through the normal profile and using a varied range of techniques: thrombin generation, plasmin generation, Fibrinography, Fibrinography in "fibrinolysis" mode, confocal microscopy, thromboelastometry and X-ray diffraction at small angles.We have highlighted the relationship between the amount of thrombin present during clot formation and the clot structure. Indeed, the more thrombin there is, the lower the protofibrils number per fiber and the greater the number of fibers. In addition, we correlated the initiation time of lateral fibers aggregation in Fibrinography with the initiation of plasmin generation. We have thus demonstrated the production of an abnormal fibrin clot structure in the presence of dabigatran, thanks to the combined use of confocal microscopy and Fibrinography.This multimodal analysis of the clot structure under different conditions provides additional information to the scientific community to better understand the mechanisms of fibrin clot formation
Analyse de la structure du caillot en conditions physiologiques et pathologiques
Physiologically, the blood function of the clot is to stop bleeding following a vascular breach. Initially, platelets stop blood flow, quickly supported by the formation of a fibrin fibers network that strengthens and gives properties to resist the blood pressure and fibrinolysis. Fibrinogen is the basic element of the fibrin network. During a vascular breach, the release of tissue factor triggers the coagulation cascade that results in the conversion of fibrinogen to fibrin monomers by the action of thrombin. These aggregate longitudinally to form protofibrils, then laterally to form a network of fibrin fibers.To date, many stages of the clot formation have been described in detail in the literature, however the mechanisms and driving forces of the lateral aggregation of protofibrils are still poorly understood.During this work, we studied different coagulation profiles: from hypo-coagulant to hyper-coagulant, through the normal profile and using a varied range of techniques: thrombin generation, plasmin generation, Fibrinography, Fibrinography in "fibrinolysis" mode, confocal microscopy, thromboelastometry and X-ray diffraction at small angles.We have highlighted the relationship between the amount of thrombin present during clot formation and the clot structure. Indeed, the more thrombin there is, the lower the protofibrils number per fiber and the greater the number of fibers. In addition, we correlated the initiation time of lateral fibers aggregation in Fibrinography with the initiation of plasmin generation. We have thus demonstrated the production of an abnormal fibrin clot structure in the presence of dabigatran, thanks to the combined use of confocal microscopy and Fibrinography.This multimodal analysis of the clot structure under different conditions provides additional information to the scientific community to better understand the mechanisms of fibrin clot formation.Physiologiquement, le caillot sanguin a pour fonction lâarrĂȘt dâun saignement consĂ©cutif Ă une brĂšche vasculaire. Dans un premier temps, ce sont les plaquettes sanguines qui stoppent lâĂ©panchement sanguin, rapidement soutenues par la formation dâun rĂ©seau de fibres de fibrine qui consolide et confĂšre au caillot les propriĂ©tĂ©s nĂ©cessaires pour rĂ©sister Ă la pression sanguine et Ă la fibrinolyse. Le fibrinogĂšne est lâĂ©lĂ©ment de base du rĂ©seau de fibrine. Lors dâune brĂšche vasculaire, la libĂ©ration de facteur tissulaire entraine le dĂ©clenchement de la cascade de coagulation qui aboutit Ă la transformation du fibrinogĂšne en monomĂšres de fibrine par lâaction de la thrombine. Ceux-ci sâagrĂšgent longitudinalement pour former des protofibrilles, puis latĂ©ralement pour former un rĂ©seau de fibres de fibrine.A ce jour, de nombreuses Ă©tapes de formation du caillot ont Ă©tĂ© dĂ©crites en dĂ©tail dans la littĂ©rature, cependant les mĂ©canismes et les forces motrices de lâagrĂ©gation latĂ©rale des protofibrilles sont encore mal compris.Lors de ce travail, nous avons Ă©tudiĂ© diffĂ©rents profils de coagulation : de lâhypo-coagulant Ă lâhypercoagulant, en passant par le profil normal et en utilisant un panel variĂ© de techniques : gĂ©nĂ©ration de thrombine, gĂ©nĂ©ration de plasmine, Fibrinographie, Fibrinographie en mode « fibrinolyse », microscopie confocale, thromboĂ©lastomĂ©trie et diffraction des rayons X aux petits angles.Nous avons mis en Ă©vidence la relation entre la quantitĂ© de thrombine prĂ©sente lors de la formation dâun caillot et la structure de celui-ci. En effet, Plus il y a de thrombine, plus le nombre de protofibrilles par fibre est faible et plus le nombre de fibres est important. De plus, nous avons corrĂ©lĂ© le temps dâinitiation de lâagrĂ©gation latĂ©rale des fibres en Fibrinographie avec lâinitiation de la gĂ©nĂ©ration de plasmine. Nous avons ainsi mis en Ă©vidence la production dâune structure du caillot de fibrine anormale en prĂ©sence de dabigatran, grĂące Ă lâutilisation combinĂ©e de la microscopie confocale et de la Fibrinographie.Cette analyse multimodale de la structure du caillot dans diffĂ©rentes conditions apporte des informations supplĂ©mentaires Ă la communautĂ© scientifique, pour permettre de mieux comprendre les mĂ©canismes de formation des caillots de fibrine
Les rejets radioactifs des installations nucléaires
Comme toute industrie, et Ă vrai dire comme toute activitĂ© humaine, l'industrie nuclĂ©aire gĂ©nĂšre des sous-produits gazeux, liquides ou solides qui ne peuvent, dans l'Ă©tat actuel des technologies disponibles, donner lieu Ă valorisation. Ainsi le fonctionnement normal d'une installation produit des effluents : certains sont traitĂ©s par concentration et mis sous forme de dĂ©chets solides qui sont conditionnĂ©s, entreposĂ©s et en dĂ©finitive stockĂ©s. D'autres ne peuvent qu'ĂȘtre traitĂ©s, filtrĂ©s, diluĂ©s et contrĂŽlĂ©s avant dispersion dans l'environnement : ce sont les rejets.
Les conditions de rejet sont rigoureusement réglementées et contrÎlées de maniÚre à garantir un trÚs faible impact sur l'environnement et une parfaite innocuité sanitaire, en tenant compte, en particulier, dans la chaßne alimentaire, de phénomÚnes possibles de concentration par certaines espÚces. Dans ce qui suit, nous ne nous intéresserons qu'aux rejets d'éléments radioactifs
Un bilan Ă deux voix sur le pouvoir d'agir des habitants dans les Forum Agri-citoyens
International audienc
IntĂ©rĂȘt du test de diagnostic rapide du streptocoque (TDR) chez l'enfant (Ă©valuation au sein d'un service d'accueil des urgences et en pratique libĂ©rale)
Objectifs : le premier objectif est d'Ă©valuer l'intĂ©rĂȘt de l'utilisation du test de diagnostic rapide des angines (TDR) au pĂŽle spĂ©cialisĂ© des urgences (POSU) de l'hĂŽpital d'enfants. Le deuxiĂšme objectif est d'Ă©valuer la pratique courante des pĂ©diatres libĂ©raux de Nancy en terme de TDR. MĂ©thodologie : une Ă©tude a Ă©tĂ© rĂ©alisĂ©e auprĂšs de 118 patients ayant bĂ©nĂ©ficiĂ© du TDR au POSU pĂ©diatrique. Un questionnaire a Ă©tĂ© envoyĂ© Ă 20 pĂ©diatres libĂ©raux de Nancy comportant des questions sur leur utilisation du TDR. RĂ©sultats : au POSU, 14 % des TDR rĂ©alisĂ©s ont posĂ© des difficultĂ©s de rĂ©alisation et d'interprĂ©tation ; 57 % de motifs de consultation non ORL aboutissent Ă la rĂ©alisation d'un TDR ; l'utilisation du TDR a diminuĂ© la prescription d'antibiotiques au POSU ; il faut rĂ©aliser des TDR mĂȘme Ă des enfants de moins de trois ans ; les recommandations de l'AFSSAPS sont bien suivies au POSU. Pour les pĂ©diatres libĂ©raux, le TDR est un outil facile Ă utiliser, ayant modifiĂ© leurs pratiques en terme de prescription d'antibiotiques.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Impact of four direct oral anticoagulants on rotational thromboelastometry (ROTEM)
International audienc
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