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1.
Rev Epidemiol Sante Publique ; 71(2): 101424, 2023 Apr.
Artigo em Francês | MEDLINE | ID: mdl-36780726

RESUMO

In public health, intervention is an object of research and evaluation which, over time, has given rise to numerous approaches. The first part of the article proposes to reposition intervention research in population health and intervention evaluation on a continuum. Although the former has a more cognitive objective and the latter a more pragmatic objective, they are not mutually exclusive. The distinction between these two practices is based on the predominance of the following characteristics: the objectives pursued, the scope of the investigations, the regulatory constraints, the financing obtained, the ethical approaches taken, and the deliverables established. The second part of the article offers a glance different fields and approaches within the continuum between these two poles: Health Technology Assessment, Health Services Research and Implementation Research. While all of them have the study of health interventions at their core, but each has developed through specialisation in one or the other type of intervention, in a particular scope or context, in certain evaluation questions, or in specific approaches. all as gateways to the study of public health intervention, these different approaches are by no means mutually exclusive.


Assuntos
Saúde Pública , Avaliação da Tecnologia Biomédica , Humanos , Pesquisa sobre Serviços de Saúde
2.
Rev Epidemiol Sante Publique ; 71(4): 101847, 2023 Aug.
Artigo em Francês | MEDLINE | ID: mdl-37167813

RESUMO

INTRODUCTION: There is growing evidence on the ethical challenges raised by cluster randomized trials. This specificity is not reflected in the legal texts regulating research, which creates difficulties for researchers implementing these experimental designs. The Ottawa Statement (Weijer et al. 2012) aims to provide detailed guidance on the ethical design, conduct and assessment of cluster trials. More broadly aims to help research stakeholders and decision-makers to make informed ethical decisions regarding the particularity of these experimental designs. It seems that this international statement, written in English, is not sufficiently accessible to all of the French professionals involved in health research. The aim of this article is to provide these professionals with a contextualized and illustrated French translation of the "Ottawa statement". METHOD: . The "complex design" working group of the RECaP network (Research in Clinical Epidemiology and Public Health), carried out this work. A first version was discussed by the authors in several meetings. It was completed by contextual explanations and examples of French studies currently conducted by the authors. The final version was obtained by consensus and validated by the group. RESULTS: . This work reports 15 recommendations grouped into 7 key questions: How to justify cluster design? How to submit an article to an ethics committee? How to identify research participants? How and when to obtain informed consent? Who are the gatekeepers? How to assess benefits and harm? How to protect vulnerable participants? Each of these recommendations is specific to cluster trials. The recommendations are explained and detailed through concrete examples. CONCLUSION: Without interfering with current French laws, this work provides a framework for the organization, conduct and ethical assessment of cluster randomized trials in France. In the present-day context, it is essential that all concerned groups can base their decisions on recommendations in line with the elementary principles of health research ethics.


Assuntos
Comitês de Ética em Pesquisa , Projetos de Pesquisa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Consentimento Livre e Esclarecido , Ética em Pesquisa
3.
Rev Epidemiol Sante Publique ; 70(5): 215-221, 2022 Oct.
Artigo em Francês | MEDLINE | ID: mdl-35879195

RESUMO

OBJECTIVES: The transition from experimentation to the scaling up of organizational innovations in public health is arduous. The innovation process requires back-up in view of enhancing the chances of success and generalization. The aim of this article is to present the development of a guide to support the description and analysis of organizational innovations in public health. METHOD: The mobilization of two analysis and description tools, ASTAIRE and TIDIeR, made it possible to select the innovation criteria to be considered for generalization. Collective discussions between actors, decision-makers and researchers and individual interviews with the latter refined and completed the proposed guide, which was reread by experts and tested by project leaders, thereby improving its accuracy and usability. RESULTS: The guide puts forward a two-step approach: i) to describe innovation at two levels: on the one hand, intervention methods, and on the other hand, interventional, population or contextual components corresponding to 27 criteria and ii) to assess the transferability of the innovation by distinguishing its key functions, its formal elements and the margins of maneuver to be maintained. DISCUSSION: The guide presents a modular vision of innovations and leaves room for reflection on its mechanisms. It favors the synchronization of innovations with the existing system and their mutualization. CONCLUSIONS: By putting forward a standardised description of organizational innovations in health and analyzing their effectiveness, the tool can effectively contribute to the development of effective, adaptable and generalizable projects, and thereby contribute to progress in public health.


Assuntos
Serviços de Saúde , Saúde Pública , Coleta de Dados , Humanos , Inovação Organizacional
4.
J Physiol ; 599(19): 4415-4426, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34411300

RESUMO

Ryanodine receptors (RyRs) are intracellular Ca2+ release channels ubiquitously expressed in various cell types. RyRs were extensively studied in striated muscle cells due to their crucial role in muscle contraction. In contrast, the role of RyRs in Ca2+ signalling and functions in non-excitable cells, such as T lymphocytes, remains poorly understood. Expression of different isoforms of RyRs was shown in primary T cells and T cell lines. In T cells, RyRs co-localize with the plasmalemmal store-operated Ca2+ channels of the Orai family and endoplasmic reticulum Ca2+ sensing Stim family proteins and are activated by store-operated Ca2+ entry and pyridine nucleotide metabolites, the intracellular second messengers generated upon stimulation of T cell receptors. Experimental data indicate that together with d-myo-inositol 1,4,5-trisphosphate receptors, RyRs regulate intercellular Ca2+ dynamics by controlling Ca2+ concentration within the lumen of the endoplasmic reticulum and, consequently, store-operated Ca2+ entry. Gain-of-function mutations, genetic deletion or pharmacological inhibition of RyRs alters T cell Ca2+ signalling and effector functions. The picture emerging from the collective data shows that RyRs are the essential regulators of T cell Ca2+ signalling and can be potentially used as molecular targets for immunomodulation or T cell-based diagnostics of the disorders associated with RyRs dysregulation.


Assuntos
Cálcio , Canal de Liberação de Cálcio do Receptor de Rianodina , Cálcio/metabolismo , Sinalização do Cálcio , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Antígenos de Linfócitos T , Rianodina , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Linfócitos T
5.
Rev Epidemiol Sante Publique ; 69(4): 235-240, 2021 Aug.
Artigo em Francês | MEDLINE | ID: mdl-34053796

RESUMO

Given today's evolution of the healthcare system, organizational transformations, technological developments and major challenges, innovation has taken on primordial importance. In this context and with considerable support, many experimentations have taken place. Unfortunately, few have managed to scale up. What results is a congeries of innovations without a future, possibly avoidable squandering of resources, a number of missed opportunities, and the grim prospect of inventor burnout. As regards prevention, innovation is at the heart of an anticipated "preventive transition" of the health system that has yet to achieve operational status. In this article we attempt to redesign the contours of innovation in health, considering it first and foremost in regard to its social utility. We will go on to explore the limitations of innovative practices that delay the arrival of advances in health. Four types of obstacles appear: faulty evaluation; insufficient dialogue between researchers, stakeholders and decision-makers; lack of visibility and, finally, conceptions and perceptions of innovation characterized by tunnel vision. In the concluding section of this paper, we will present several tracks through which the innovation process could be impelled to drive health system transformation. They consist in: (i) incorporating an evaluative and comprehensive research into innovation processes, (ii) elaborating "bottom-up" approaches giving special consideration to innovations instigated by stakeholders and brought to fruition under real-life conditions, (iii) breaking from standardization by thinking from the outset of the adaptability of innovations and, finally, (iv) tying in the experimental approach with a decision-making process.


Assuntos
Atenção à Saúde , Programas Governamentais , Humanos , Projetos de Pesquisa
6.
Rev Epidemiol Sante Publique ; 68(2): 117-123, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-31974001

RESUMO

The recent opening of massive health databases, as well as the development of methods and tools adapted to their data processing, questions the French model of "morbidity registry". In France in 2019, nearly 61 health registries were operating. As defined by law, these registries identify exhaustively all patients with a given disease in a given territory. Established several decades ago, these registries are part of the French surveillance system that is used for research and evaluation purposes. Since the advent of recent technological progress, large-scale databases are made available to researchers and it is possible with these databases to answer questions initially assigned to the registries. What is the place of such registries in this new context: are they obsolete or still useful? Should they be opposed to the new tools or are they complementary to them, and if so, what is their place in the new French public health ecosystem? The objective of this work was to assess the roles and missions of existing registries and to reflect on their positioning in this new environment. The French model of registry is sometimes questioned because of the complexity of its circuits, requiring a significant amount of human resources. However, the data that constitute them, validated by cross-checking information from several sources, are of very high quality, and make it possible to validate the data in the new databases (National Health Data System (NSDS) or Hospital Data Warehouses). Registries and new databases are in fact complementary, and far from jeopardizing this model, the recent opening of these databases represents an opportunity for registries to modernize their operations and respond to new missions.


Assuntos
Big Data , Bases de Dados Factuais/tendências , Morbidade , Saúde Pública/tendências , Sistema de Registros , Big Data/provisão & distribuição , Bases de Dados Factuais/normas , Bases de Dados Factuais/provisão & distribuição , Registros Eletrônicos de Saúde/organização & administração , Registros Eletrônicos de Saúde/normas , Registros Eletrônicos de Saúde/tendências , França/epidemiologia , Gestão da Informação em Saúde/organização & administração , Gestão da Informação em Saúde/normas , Gestão da Informação em Saúde/tendências , Humanos , Disseminação de Informação/métodos , Modelos Organizacionais , Prática Profissional/organização & administração , Prática Profissional/normas , Prática Profissional/tendências , Papel Profissional , Saúde Pública/estatística & dados numéricos , Sistema de Registros/normas , Sistema de Registros/estatística & dados numéricos
7.
Wiad Lek ; 73(1): 203-207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32124836

RESUMO

The objective of our study was to interpret and discuss atypical multiple myeloma case. The article describes the case of clinical observation of a patient K, in which manifestations of chronic kidney disease and circulatory failure prevailed in clinical picture of the disease. The authors recommended an X-ray examination of skull and pelvic bones as a screening method suitable for elderly people with symptoms of chronic renal insufficiency and chronic bone and muscle pain resistant to treatment.


Assuntos
Diagnóstico Diferencial , Mieloma Múltiplo , Osso e Ossos , Humanos , Radiografia
8.
Rev Epidemiol Sante Publique ; 66(6): 375-383, 2018 Nov.
Artigo em Francês | MEDLINE | ID: mdl-30340796

RESUMO

BACKGROUND: Targeted interventions among vulnerable youth populations represent an important approach to the reduction of health inequalities. We must, however, ensure that impacts are not unequally distributed according to the range of resources available to them. We explore these concerns among youth in vocational training to be enrolled in a smoking cessation intervention by describing (1) their socio-economic profile and (2) the association between their socioeconomic characteristics, their smoking practices, and key factors that could be targeted in interventions. METHODS: A total of 234 young people aged 15-20 years were recruited in three centers in the Lorraine region in France in 2016-2017 as part of the Social Network and Tobacco Cessation (Réseau social et sevrage tabagique [RESIST]) study. We measured participants' socio-economic characteristics using their parents' education and occupational grade. We examined the associations of these characteristics with participants' smoking habits, intention to quit, nicotine dependence, presence of smokers in their network, and representation of a young smoker. We examined the associations between variables with bivariate tests depending on the nature of the variables. RESULTS: Participants were more likely to be from a socio-professional background more modest than the national average (56% versus 33%), but still exhibited considerable socioeconomic variability. Smoking status did not vary significantly according to the educational level of the participants' parents (from 52% to 57%, P=0.78) or occupational grade (from 52% to 58%, P=0.35). Compared to participants whose parents had completed a professional or pre-university degree, participants with parents in the lowest education category were less likely to report not intending to quit (P=0.01) and more likely to report seriously considering to quit in the next six months (P=0.03) and to have already tried to quit but failed (P=0.01). CONCLUSION: It is tempting to define youth in vocational training as a homogeneous group, especially when they share the same school environment, employment status, and income. Our results, however, highlight substantial variability in their socioeconomic profiles and smoking characteristics. Researchers are encouraged to further consider these equity issues to contribute to the reduction of health inequalities.


Assuntos
Comportamento do Adolescente , Fumar/epidemiologia , Educação Vocacional/estatística & dados numéricos , Adolescente , Adulto , Feminino , França/epidemiologia , Humanos , Masculino , Fatores Socioeconômicos , Estudantes/estatística & dados numéricos , Adulto Jovem
10.
Prog Urol ; 24(9): 572-80, 2014 Jul.
Artigo em Francês | MEDLINE | ID: mdl-24975792

RESUMO

INTRODUCTION: Prostate-specific antigen (PSA) testing is high in France. The aim of this study was to estimate their frequency and those of biopsy and newly diagnosed cancer (PCa) according to the presence or absence of treated benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: This study concerned men 40 years and older covered by the main French national health insurance scheme (73 % of all men of this age). Data were collected from the national health insurance information system (SNIIRAM). This database comprehensively records all of the outpatient prescriptions and healthcare services reimbursed. This information are linked to data collected during hospitalisations. RESULTS: The frequency of men without diagnosed PCa (10.9 millions) with at least one PSA test was very high in 2011 (men aged 40 years and older: 30 %, 70-74 years: 56 %, 85 years and older: 33 % and without HBP: 25 %, 41 % and 19 %). Men with treated BPH totalized 9 % of the study population, but 18 % of the men with at least one PSA test, 44 % of those with at least one prostate biopsy and 40 % of those with newly managed PCa. Over a 3-year period, excluding men with PCa, 88 % of men with BPH had at least one PSA test and 52 % had three or more PSA tests versus 52 % and 15 % for men without BPH. One year after PSA testing, men of 55-69 years with BPH more frequently underwent prostate biopsy than those without BPH (5.4 % vs 1.8 %) and presented PCa (1.9 % vs 0.9 %). CONCLUSIONS: PSA testing frequencies in France are very high even after exclusion of men with BPH, who can be a group with more frequent managed PCa. LEVEL OF EVIDENCE: 4.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , França , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Neoplasias da Próstata/complicações
11.
J Biol Chem ; 287(44): 37233-44, 2012 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-22948152

RESUMO

The expression and functional significance of ryanodine receptors (RyR) were investigated in resting and activated primary human T cells. RyR1, RyR2, and RyR3 transcripts were detected in human T cells. RyR1/2 transcript levels increased, whereas those of RyR3 decreased after T cell activation. RyR1/2 protein immunoreactivity was detected in activated but not in resting T cells. The RyR agonist caffeine evoked Ca(2+) release from the intracellular store in activated T cells but not in resting T cells, indicating that RyR are functionally up-regulated in activated T cells compared with resting T cells. In the presence of store-operated Ca(2+) entry (SOCE) via plasmalemmal Ca(2+) release-activated Ca(2+) (CRAC) channels, RyR blockers reduced the Ca(2+) leak from the endoplasmic reticulum (ER) and the magnitude of SOCE, suggesting that a positive feedback relationship exists between RyR and CRAC channels. Overexpression of fluorescently tagged RyR2 and stromal interaction molecule 1 (STIM1), an ER Ca(2+) sensor gating CRAC channels, in HEK293 cells revealed that RyR are co-localized with STIM1 in the puncta formed after store depletion. These data indicate that in primary human T cells, the RyR are coupled to CRAC channel machinery such that SOCE activates RyR via a Ca(2+)-induced Ca(2+) release mechanism, which in turn reduces the Ca(2+) concentration within the ER lumen in the vicinity of STIM1, thus facilitating SOCE by reducing store-dependent CRAC channel inactivation. Treatment with RyR blockers suppressed activated T cell expansion, demonstrating the functional importance of RyR in T cells.


Assuntos
Sinalização do Cálcio , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Linfócitos T/metabolismo , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Proliferação de Células , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Expressão Gênica , Células HEK293 , Humanos , Células Jurkat , Ativação Linfocitária , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Molécula 1 de Interação Estromal , Linfócitos T/fisiologia , Regulação para Cima
12.
Public Health ; 127(9): 860-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23787223

RESUMO

OBJECTIVE: To describe the reporting of public health research in Francophone sub-Saharan Africa (FSA). STUDY DESIGN: A bibliometric research study of scientific public health publications in FSA, which includes 24 countries and approximately 260 million people. METHODS: Two researchers analysed original articles published in 2007 in the medical or social sciences fields and indexed in Scopus. At least one co-author of articles had to be based in FSA. The analysis focused on research field, public health function (WHO classification), FSA country author's affiliation, language, journal type and global burden of disease (WHO classification). RESULTS: Of 1047 articles retrieved by the search, 212 were from the public health field. The number of articles per country varied from 0 to 36. Public health functions examined were health service research (24.5%), health monitoring (27.4%), prevention (15%) and legislation (0.5%). The distribution of health needs described in the articles was close to that of the WHO data for Africa for 2004: infectious and parasitic diseases (70% vs 54%), maternal and perinatal conditions (15% vs 17%), non-communicable diseases (15.6% vs 21%), and injuries (0.5% vs 8%). CONCLUSION: The areas reported in published articles from sub-Saharan Africa reflect the health needs distribution in Africa; however, the number of publications is low, particularly for prevention. In light of the current focus on evidence-based public health, this study questions whether the international scientific community adequately considers the expertise and perspectives of African researchers and professionals.


Assuntos
Bibliometria , Pesquisa Biomédica , Necessidades e Demandas de Serviços de Saúde , Saúde Pública , África Subsaariana , Humanos
13.
Diabetologia ; 55(7): 1953-62, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22460763

RESUMO

AIMS/HYPOTHESIS: Previous studies have suggested an increased risk of bladder cancer with pioglitazone exposure. We aimed to investigate the association between pioglitazone exposure and bladder cancer in France. METHODS: This cohort study involved use of data from the French national health insurance information system (Système National d'Information Inter-régimes de l'Assurance Maladie; SNIIRAM) linked with the French hospital discharge database (Programme de Médicalisation des Systèmes d'Information; PMSI). The cohort included patients aged 40 to 79 years who filled a prescription for a glucose-lowering drug in 2006. The cohort was followed for up to 42 months. Pioglitazone exposure was modelled as a time-dependent variable and defined by having filled at least two prescriptions over a 6-month period. Incident cases of bladder cancer were identified by a discharge diagnosis of bladder cancer combined with specific aggressive treatment. Statistical analyses involved a multivariate Cox model adjusted for age, sex and exposure to other glucose-lowering drugs. RESULTS: The cohort included 1,491,060 diabetic patients, 155,535 of whom were exposed to pioglitazone. We found 175 cases of bladder cancer among exposed patients and 1,841 among non-exposed patients. Incidence rates were 49.4 and 42.8 per 100,000 person-years, respectively. Pioglitazone exposure was significantly associated with bladder cancer incidence (adjusted HR 1.22 [95% CI 1.05, 1.43]). We observed a dose-effect relationship, with a significantly increased risk for high cumulative doses (≥ 28,000 mg, adjusted HR 1.75 [95% CI 1.22, 2.50]) and long duration of exposure (≥ 24 months, adjusted HR 1.36 [1.04, 1.79]). CONCLUSIONS/INTERPRETATION: In this cohort of diabetic patients from France, pioglitazone exposure was significantly associated with increased risk of bladder cancer.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Tiazolidinedionas/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Esquema de Medicação , Feminino , Seguimentos , França/epidemiologia , Humanos , Hipoglicemiantes/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pioglitazona , Modelos de Riscos Proporcionais , Fatores de Risco , Tiazolidinedionas/administração & dosagem , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/prevenção & controle
14.
Vaccine ; 40(2): 178-182, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34863619

RESUMO

France is one of the most vaccine-hesitant countries in the world, including for coronavirus disease 2019 (COVID-19). After 10 months of restrictive measures and media coverage of the dangers of COVID-19, French attitudes towards a vaccine continue to deteriorate. The communication strategies of the government have not helped; in fact, they have made the situation worse. Empirical studies on the national strategy for management of the COVID-19 pandemic in France have shed light on the reasons for vaccine hesitancy. These studies have identified four pillars for the vaccination strategy: i) Communication regarding the importance of herd immunity, ii) making healthcare workers the focus of the vaccination campaign, iii) citizen mobilization and guaranteed consultations, and iv) access to free vaccines without delay. This paper discusses the evidence supporting this strategy.


Assuntos
COVID-19 , Vacinas , Vacinas contra COVID-19 , França , Humanos , Programas de Imunização , Pandemias , SARS-CoV-2 , Vacinação , Hesitação Vacinal
15.
Artigo em Inglês | MEDLINE | ID: mdl-21548444

RESUMO

These guidelines represent a consensus among experts on hypersensitivity reactions occurring after transfusion of blood components. They cover recognition, investigation, treatment, and prevention of such reactions. Implemented in France under the auspices of the French Medicines and Healthcare Products Regulatory Agency (AFSSAPS) and based on current knowledge, research, and experience, they aim to provide effective and easily teachable means of further improving the quality of hemovigilance databases, promote interest in this field, and help identify possible mechanisms and at-risk patient groups.


Assuntos
Transfusão de Componentes Sanguíneos/efeitos adversos , Transfusão de Componentes Sanguíneos/normas , Hipersensibilidade/etiologia , Hipersensibilidade/prevenção & controle , França , Política de Saúde , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/terapia , Guias de Prática Clínica como Assunto
16.
Rev Epidemiol Sante Publique ; 59(4): 270-6, 2011 Aug.
Artigo em Francês | MEDLINE | ID: mdl-21752562

RESUMO

BACKGROUND: Most smokers start smoking during adolescence and become dependent before 20 years old. In France, vocational trainees are a population not much explored. The objective of our study is to present tobacco use characteristics among apprentices in Vocational Centers (VC). METHODS: This cross-sectional exhaustive study covered 1814 students (among whose 943 smokers) entering in a 1st year of the eight participating Vocational Centers in the Lorraine region (Eastern France, 2.3 million inhabitants, 16,500 vocational trainees), during the school years 2007-2008 and 2008-2009. Data collection concerned the sociocultural environment, tobacco use habits, degree of dependency to tobacco and co-addictions. RESULTS: Among the study population, 52.0% declared they were smokers among whom 89.4% daily smokers, and 5.7% were ex-smokers. The average age of tobacco use initiation was 12.1 years (standard deviation [SD]=2.1) and the average age at inception of regular cigarette smoking was 13.8 years (SD=1.6). Current consumption of the smokers was 12.8 cigarettes per day (SD=7.8). The average score of smoking addiction was 6.1 (SD=2.8), according to the Hooked On Nicotine checklist test (score from 0 to 10=strongly dependent). Finally, 37.1% of students (58.9% among smokers) smoked or have smoked cannabis. CONCLUSION: The high prevalence of smoking in Vocational Centers, the early start of tobacco use and the high tobacco consumption among apprentices show that they are overexposed compared to the general population of adolescents. In addition, these young people are already dependant to tobacco use. This underlines the need of specific measures dedicated to this population that amounts to 361,500 individuals in France.


Assuntos
Fumar/epidemiologia , Adolescente , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Instituições Acadêmicas , Estudantes , Educação Vocacional , Adulto Jovem
17.
Channels (Austin) ; 15(1): 67-78, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33356832

RESUMO

In the last 5 years inhibitors of the potassium channel KV1.3 have been shown to reduce neuroinflammation in rodent models of ischemic stroke, Alzheimer's disease, Parkinson's disease and traumatic brain injury. At the systemic level these beneficial actions are mediated by a reduction in microglia activation and a suppression of pro-inflammatory cytokine and nitric oxide production. However, the molecular mechanisms for the suppressive action of KV1.3 blockers on pro-inflammatory microglia functions was not known until our group recently demonstrated that KV1.3 channels not only regulate membrane potential, as would be expected of a voltage-gated potassium channel, but also play a crucial role in enabling microglia to resist depolarizations produced by the danger signal ATP thus regulating calcium influx through P2X4 receptors. We here review the role of KV1.3 in microglial signaling and show that, similarly to their role in T cells, KV1.3 channels also regulated store-operated calcium influx in microglia.


Assuntos
Microglia , Doença de Alzheimer , Sinalização do Cálcio , Potenciais da Membrana , Doenças Neuroinflamatórias , Canais de Potássio de Abertura Dependente da Tensão da Membrana
18.
Front Physiol ; 12: 770820, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35027891

RESUMO

Ryanodine receptors (RyRs), the intracellular Ca2+ release channels, are expressed in T lymphocytes and other types of immune cells. Modulation of RyRs has been shown to affect T cell functions in vitro and immune responses in vivo. The effects of modulation of RyRs on the development of autoimmune diseases have not been investigated. Here we studied how modulation of RyRs through administration of RyR inhibitor dantrolene or introducing a gain-of-function RYR1-p.R163C mutation affects clinical progression of experimental autoimmune encephalomyelitis (EAE) in mice, a T cell-mediated autoimmune neuroinflammatory disease. We found that daily intraperitoneal administration of 5 or 10 mg/kg dantrolene beginning at the time of EAE induction significantly reduced the severity of EAE clinical symptoms and dampened inflammation in the spinal cord. The protective effect of dantrolene on EAE was reversible. Dantrolene administration elicited dose-dependent skeletal muscle weakness: mice that received 10 mg/kg dose developed a waddling gait, while 5 mg/kg dantrolene dose administration produced a reduction in four-limb holding impulse values. Mice bearing the gain-of-function RYR1-p.R163C mutation developed the EAE clinical symptoms faster and more severely than wild-type mice. This study demonstrates that RyRs play a significant role in EAE pathogenesis and suggests that inhibition of RyRs with low doses of dantrolene may have a protective effect against autoimmunity and inflammation in humans.

19.
Cell Calcium ; 93: 102325, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310301

RESUMO

Gain-of-function RyR1-p.R163C mutation in ryanodine receptors type 1 (RyR1) deregulates Ca2+ signaling and mitochondrial function in skeletal muscle and causes malignant hyperthermia in humans and mice under triggering conditions. We investigated whether T lymphocytes from heterozygous RyR1-p.R163C knock-in mutant mice (HET T cells) display measurable aberrations in resting cytosolic Ca2+ concentration ([Ca2+]i), Ca2+ release from the store, store-operated Ca2+ entry (SOCE), and mitochondrial inner membrane potential (ΔΨm) compared with T lymphocytes from wild-type mice (WT T cells). We explored whether these variables can be used to distinguish between T cells with normal and altered RyR1 genotype. HET and WT T cells were isolated from spleen and lymph nodes and activated in vitro using phytohemagglutinin P. [Ca2+]i and ΔΨm dynamics were examined using Fura 2 and tetramethylrhodamine methyl ester fluorescent dyes, respectively. Activated HET T cells displayed elevated resting [Ca2+]i, diminished responses to Ca2+ mobilization with thapsigargin, and decreased rate of [Ca2+]i elevation in response to SOCE compared with WT T cells. Pretreatment of HET T cells with ryanodine or dantrolene sodium reduced disparities in the resting [Ca2+]i and ability of thapsigargin to mobilize Ca2+ between HET and WT T cells. While SOCE elicited dissipation of the ΔΨm in WT T cells, it produced ΔΨm hyperpolarization in HET T cells. When used as the classification variable, the amplitude of thapsigargin-induced Ca2+ transient showed the best promise in predicting the presence of RyR1-p.R163C mutation. Other significant variables identified by machine learning analysis were the ratio of resting cytosolic Ca2+ level to the amplitude of thapsigargin-induced Ca2+ transient and an integral of changes in ΔΨm in response to SOCE. Our study demonstrated that gain-of-function mutation in RyR1 significantly affects Ca2+ signaling and mitochondrial fiction in T lymphocytes, which suggests that this mutation may cause altered immune responses in its carrier. Our data link the RyR1-p.R163C mutation, which causes inherited skeletal muscle diseases, to deregulation of Ca2+ signaling and mitochondrial function in immune T cells and establish proof-of-principle for in vitro T cell-based diagnostic assay for hereditary RyR1 hyperfunction.


Assuntos
Sinalização do Cálcio , Espaço Intracelular/metabolismo , Hipertermia Maligna/imunologia , Mitocôndrias/metabolismo , Linfócitos T/imunologia , Animais , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Genótipo , Ativação Linfocitária/efeitos dos fármacos , Aprendizado de Máquina , Hipertermia Maligna/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Proteínas Mutantes/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Tapsigargina/farmacologia
20.
Rev Epidemiol Sante Publique ; 58(4): 277-83, 2010 Aug.
Artigo em Francês | MEDLINE | ID: mdl-20619563

RESUMO

In France, current structuring of preventive and health promotion policies has created a context favoring evidence-based actions. Yet, in health promotion and health education, interventions are very much setting dependent, potentially compromising this type of approach to health promotion. Thus, in an attempt to inform participants in health promotion in the French setting of ongoing international debates on the topic, we present the main limitations developed in literature, highlighting recent work responding to the challenge. Our analysis is focused on three points: the issue of the level of intervention and indicators to assess efficacy and effectiveness of health promotion interventions; the issue of research methodologies, their capacity to demonstrate efficacy and effectiveness of health promotion interventions and the transferability of their outcomes; the issue of the external validity of studies, and in particular the information necessary for understanding complex mechanisms of intervention. On the basis of this analysis, and with the aim of improving evidence-based health promotion practices, we propose practical perspectives in the French environment for policymakers, local practitioners and researchers. To conclude, we link this issue with the concept of knowledge transfer, which is developed in other countries.


Assuntos
Medicina Baseada em Evidências , Educação em Saúde/tendências , Promoção da Saúde/tendências , Saúde Pública/tendências , Pesquisa Biomédica/tendências , Medicina Baseada em Evidências/tendências , França , Educação em Saúde/legislação & jurisprudência , Política de Saúde , Promoção da Saúde/legislação & jurisprudência , Humanos , Saúde Pública/legislação & jurisprudência
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