L’évaluation des déterminants des paramètres hémodynamiques centraux à l’aide de la cohorte populationnelle CARTaGENE

Les maladies cardiovasculaires ont un impact considérable sur la vie des Canadiens, et de nombreux efforts ont permis d’identifier différents facteurs de risque associés à cette condition. L’hypertension artérielle représente un de ces facteurs modifiables les plus importants. Quoique l’hypertension est définie à l’aide de mesures de pression artérielle en périphérie, il devient de plus en plus apparent que la mesure de pression centrale et de ses composantes auraient des avantages au niveau de la prédiction de la survenue d’événements cardiovasculaires. Le présent mémoire vise à mieux caractériser deux déterminants de cette pression centrale, le traitement antihypertenseur à base de bêtabloqueurs et l’insuffisance rénale chronique précoce. En utilisant les données recueillies dans la banque de données populationnelle CARTaGENE, il a été possible à l’aide d’analyses statistiques par appariement basé sur le coefficient de propension de démontrer que l’utilisation d’agents antihypertensifs de type bêtabloqueurs était associée à un profil hémodynamique central défavorable. Ainsi, les individus recevant ces agents avaient une pression centrale et une amplification artérielle plus élevées que des individus du groupe contrôle apparié et ce, malgré une pression périphérique identique. Cet effet semblait être incomplètement expliqué par la réduction du rythme cardiaque associé à l’utilisation de bêtabloqueurs. Aussi, il a été démontré que l’insuffisance rénale chronique de stade 3 (débit de filtration glomérulaire estimé entre 30 et 60 mL/min/1.73m2) n’était pas associée à une élévation des paramètres hémodynamiques centraux, contrairement à ce qui avait déjà été décrit chez des individus avec insuffisance rénale chronique plus avancée. De plus, le niveau d’albuminurie ne serait également pas associé à un changement du profil central dans un sous-groupe de la cohorte CARTaGENE.Cardiovascular diseases have a large impact on Canadian’s lives, and throughout the years, several risk factors associated with this condition have been identified. Hypertension represents an important of the modifiable risk factors. While high blood pressure is usually defined using peripheral blood pressure measurements, it has recently been shown that measurements of the central blood pressure and its components are more precise predictors of incident cardiovascular events. The thesis aims at better characterising mainly two determinants of central blood pressure: beta-blocker use for the treatment of hypertension and early chronic kidney disease. Using data from the CARTaGENE populational cohort and propensity score matching techniques, it was shown that beta-blockers use in the treatment of hypertension are associated with an unfavorable central hemodynamic profile. Hence, individuals receiving these agents had higher central blood pressures and arterial amplification than individuals of the matched control group, despite identical peripheral blood pressures. This effect was mostly, but not only, explained by the associated reduction of the heart rate. It was also shown that stage 3 chronic kidney disease (estimated glomerular filtration rate between 30 and 60 mL/min/1.73m2) was not associated with an increase in central hemodynamic parameters, unlike what was previously shown in individuals with more advanced chronic kidney disease. Furthermore, albuminuria was not associated with detrimental changes in the central hemodynamic profile in a subset of CARTaGENE

Expression profiling of rainbow trout testis development identifies evolutionary conserved genes involved in spermatogenesis.

Chantier qualité GAInternational audienceBACKGROUND: Spermatogenesis is a late developmental process that involves a coordinated expression program in germ cells and a permanent communication between the testicular somatic cells and the germ-line. Current knowledge regarding molecular factors driving male germ cell proliferation and differentiation in vertebrates is still limited and mainly based on existing data from rodents and human. Fish with a marked reproductive cycle and a germ cell development in synchronous cysts have proven to be choice models to study precise stages of the spermatogenetic development and the germ cell-somatic cell communication network. In this study we used 9K cDNA microarrays to investigate the expression profiles underlying testis maturation during the male reproductive cycle of the trout, Oncorhynchus mykiss. RESULTS: Using total testis samples at various developmental stages and isolated spermatogonia, spermatocytes and spermatids, 3379 differentially expressed trout cDNAs were identified and their gene activation or repression patterns throughout the reproductive cycle were reported. We also performed a tissue-profiling analysis and highlighted many genes for which expression signals were restricted to the testes or gonads from both sexes. The search for orthologous genes in genome-sequenced fish species and the use of their mammalian orthologs allowed us to provide accurate annotations for trout cDNAs. The analysis of the GeneOntology terms therefore validated and broadened our interpretation of expression clusters by highlighting enriched functions that are consistent with known sequential events during male gametogenesis. Furthermore, we compared expression profiles of trout and mouse orthologs and identified a complement of genes for which expression during spermatogenesis was maintained throughout evolution. CONCLUSION: A comprehensive study of gene expression and associated functions during testis maturation and germ cell differentiation in the rainbow trout is presented. The study identifies new pathways involved during spermatogonia self-renewal or rapid proliferation, meiosis and gamete differentiation, in fish and potentially in all vertebrates. It also provides the necessary basis to further investigate the hormonal and molecular networks that trigger puberty and annual testicular recrudescence in seasonally breeding species

OIKOS, habiter un monde commun, chapitre 2. Vers une planète inhabitable et un monde invivable ? "Se soigner"

FORTES = Formation à la transition dans l'enseignement supérieur. - Autres tirages : 2021, 2022. - La couverture porte en plus : "Climat, écologie, éthique, santé, économie, droit, démocratie, énergie, agriculture, arts..." et "Former pour transformer". - Autre contributeur : Christian Koenig (directeur de publication).International audiencePour la première fois, un collectif d'environ soixante-dix enseignants-chercheurs issus d'une grande variété de domaines (environnement, sciences du vivant, biologie, physique, économie, droit, gestion, philosophie, santé, sociologie, sciences politiques) s'est réuni pour réaliser le manuel de la "Grande Transition ". Car cette transition ne relève pas seulement de l'environnement ou de l'économie, comme on a coutume de le penser, mais touche au coeur même de nos représentations, et donc à tous les champs du savoir. L'ouvrage propose un socle de connaissances et de compétences, thématique par thématique. Il expose dans un langage clair et accessible les processus impliqués dans le réchauffement climatique et la dégradation du vivant, mais aussi les responsabilités des différents acteurs, le creusement des inégalités environnementales ou encore les mécanismes financiers qui en sont l'une des causes. Au-delà de la simple description des faits, il identifie des leviers d'action individuels et collectifs : réorganisation sociale du travail, mesures économiques, transformation des modes de vie et des façons de produire (agroécologie, communs, technologies bas carbone, etc.)..

Diagnosis and outcomes of acute kidney injury using surrogate and imputation methods for missing preadmission creatinine values

Abstract Background Missing preadmission serum creatinine (SCr) values are a common obstacle to assess acute kidney injury (AKI) diagnosis and outcomes. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines suggest using a SCr computed from the Modification of Diet in Renal Disease (MDRD) with an estimated glomerular filtration rate of 75 ml/min/1.73 m2. We aimed to identify the best surrogate method for baseline SCr to assess AKI diagnosis and outcomes. Methods We compared the use of 1) first SCr at hospital admission 2) minimal SCr over 2 weeks after intensive care unit admission 3) MDRD computed SCr and 4) Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) computed SCr to assess AKI diagnosis and outcomes. We then performed multilinear regression models to predict preadmission SCr and imputation strategies to assess AKI diagnosis. Results Our one-year retrospective cohort study included 1001 critically ill adults; 498 of them had preadmission SCr values. In these patients, AKI incidence was 25.1% using preadmission SCr. First SCr had the best agreement for AKI diagnosis (22.5%; kappa = 0.90) and staging (kappa = 0.81). MDRD, CKD-EPI and minimal SCr overestimated AKI diagnosis (26.7%, 27.1% and 43.2%;kappa = 0.86, 0.86 and 0.60, respectively). However, MDRD and CKD-EPI computed SCr had a better sensitivity than first SCr for AKI (93% and 94% vs. 87%). Eighty-eight percent of patients experienced renal recovery at least 3 months after hospital discharge. All methods except the first SCr significantly underestimated the percentage of renal recovery. In a multivariate model, age, male gender, hypertension, heart failure, undergoing surgery and log first SCr best predicted preadmission SCr (adjusted R2 = 0.56). Imputation methods with first SCr increased AKI incidence to 23.9% (kappa = 0.92) but not with MDRD computed SCr (26.7%;kappa = 0.89). Conclusion In our cohort, first SCr performed better for AKI diagnosis and staging, as well as for renal recovery after hospital discharge than MDRD, CKD-EPI or minimal SCr. However, MDRD SCr and CKD-EPI SCr improved AKI diagnosis sensitivity. Imputation methods minimally increased agreement for AKI diagnosis

Identification of androgen-responsive genes in fish testis: relevance to the male gonad development and the regulation of spermatogenesis

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Profiling of androgen response in rainbow trout pubertal testis: relevance to male gonad development and spermatogenesis.

International audienceThe capacity of testicular somatic cells to promote and sustain germ cell differentiation is largely regulated by sexual steroids and notably androgens. In fish species the importance of androgens is emphasized by their ability to induce sex reversal of the developing fries and to trigger spermatogenesis. Here we studied the influence of androgens on testicular gene expression in trout testis using microarrays. Following treatment of immature males with physiological doses of testosterone or 11-ketotestosterone, 418 genes that exhibit changes in expression were identified. Interestingly, the activity of testosterone appeared stronger than that of 11-ketotestosterone. Expression profiles of responsive genes throughout testis development and in isolated germ cells confirmed androgens to mainly affect gene expression in somatic cells. Furthermore, specific clusters of genes that exhibit regulation coincidently with changes in the natural circulating levels of androgens during the reproductive cycle were highlighted, reinforcing the physiological significance of these data. Among somatic genes, a phylogenetic footprinting study identified putative androgen response elements within the proximal promoter regions of 42 potential direct androgen target genes. Finally, androgens were also found to alter the germ line towards meiotic expression profiles, supporting the hypothesis of a role for the somatic responsive genes in driving germ cell fate. This study significantly increases our understanding of molecular pathways regulated by androgens in vertebrates. The highly cyclic testicular development in trout together with functions associated with regulated genes reveal potential mechanisms for androgen actions in tubule formation, steroid production, germ cell development and sperm secretion

Le mauvais goût : marginalités, ambiguïtés, paradoxes (XIXe-XXIe siècles)

La journée d’études Le mauvais goût. Marginalités, ambiguïtés, paradoxes (XIXe-XXIe siècles) s’est tenue le 23 mai 2018 à la Maison de l’étudiant Marta Pan de l’Université de Versailles – Saint-Quentin-en-Yvelines, Guyancourt.International audienceDu baroque au kitsch, du maniérisme à l'obscène, du camp au trash, du grossier au ringard, du populaire au pop, le mauvais goût a connu bien des déclinaisons à travers les âges. En dépit des anathèmes régulièrement lancés contre lui, le mauvais goût n'a pourtant de cesse de se renouveler et peut parfois même être érigé au rang de modèle esthétique : ainsi, dans le Gai Savoir, Nietzsche réclamait que le « mauvais goût [ait] son droit autant que le bon goût ». Celui-ci se réinvente sous des formes multiples, au point même d'être chargé d'une valeur positive, à la faveur de renversements de valeurs.Cette journée d'étude, centrée sur les XIXe, XXe et XXIe siècles, entend redonner tout son droit au mauvais goût, en déconstruisant les mécanismes qui tendent à le marginaliser et en tentant d'analyser les potentialités créatives, expressives et revendicatives de ce parent pauvre de l'esthétique

CENtral blood pressure Targeting: a pragmatic RAndomized triaL in advanced Chronic Kidney Disease (CENTRAL-CKD): A Clinical Research Protocol

Background: Emerging data favor central blood pressure (BP) over brachial cuff BP to predict cardiovascular and kidney events, as central BP more closely relates to the true aortic BP. Considering that patients with advanced chronic kidney disease (CKD) are at high cardiovascular risk and can have unreliable brachial cuff BP measurements (due to high arterial stiffness), this population could benefit the most from hypertension management using central BP measurements. Objective: To assess the feasibility and efficacy of targeting central BP as opposed to brachial BP in patients with CKD G4-5. Design: Pragmatic multicentre double-blinded randomized controlled pilot trial. Setting: Seven large academic advanced kidney care clinics across Canada. Patients: A total of 116 adults with CKD G4-5 (estimated glomerular filtration rate [eGFR] < 30 mL/min) and brachial cuff systolic BP between 120 and 160 mm Hg. The key exclusion criteria are 1) ≥ 5 BP drugs, 2) recent acute kidney injury, myocardial infarction, stroke, heart failure or injurious fall, 3) previous kidney replacement therapy. Methods: Double-blind randomization to a central or a brachial cuff systolic BP target (both < 130 mm Hg) as measured by a validated central BP device. The study duration is 12 months with follow-up visits every 2 to 4 months, based on local practice. All other aspects of CKD management are at the discretion of the attending nephrologist. Outcomes: Primary Feasibility : Feasibility of a large-scale trial based on predefined components. Primary Efficacy : Carotid-femoral pulse wave velocity at 12 months. Others : Efficacy (eGFR decline, albuminuria, BP drugs, and quality of life); Events (major adverse cardiovascular events, CKD progression, hospitalization, mortality); Safety (low BP events and acute kidney injury). Limitations: May be challenging to distinguish whether central BP is truly different from brachial BP to the point of significantly influencing treatment decisions. Therapeutic inertia may be a barrier to successfully completing a randomized trial in a population of CKD G4-5. These 2 aspects will be evaluated in the feasibility assessment of the trial. Conclusion: This is the first trial to evaluate the feasibility and efficacy of using central BP to manage hypertension in advanced CKD, paving the way to a future large-scale trial. Trial registration: clinicaltrials.gov (NCT05163158