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1.
BJGP Open ; 8(2)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38253400

RESUMEN

BACKGROUND: GPs are particularly vulnerable to job burnout. Tailored prevention and intervention strategies are needed. AIM: To investigate organisational, interpersonal, and individual factors contributing to exhaustion and disengagement at work among GPs. DESIGN & SETTING: We conducted a cross-sectional study in a sample of Belgian GPs. METHOD: A total of 358 doctors (73% females, 301 with complete data) completed an online anonymous questionnaire assessing job burnout, psychosocial characteristics of the work environment, perceived social support in the private domain, emotional competence, and self-compassion. RESULTS: GPs reported moderate levels of exhaustion and disengagement. Regression models showed that included factors jointly explained 69% of the variance in exhaustion and 63% in disengagement. Exhaustion was significantly predicted by female sex (ß effect size = -0.1), high perceived emotional demands (ß = 0.19), as well as low self-compassion (ß = -0.14) and low emotional competence (ß = 0.09). Disengagement was significantly predicted by low seniority (ß = -0.12) and limited opportunities for development (ß = -0.16). Both exhaustion and disengagement were predicted by low perceived quality of work (ß = -0.19 and -0.14, respectively), meaning of work (ß = -0.17 and -0.31, respectively), and role clarity (ß = 0.09 and 0.12, respectively), as well as high perceived work-life conflict (ß = 0.46 and 0.21, respectively). Moreover, GPs working in a multidisciplinary group reported lower levels of exhaustion and disengagement than those working in a monodisciplinary group or a solo practice, and this difference was associated with factors such as work-life conflict. CONCLUSION: Organisational, interpersonal, and intrapersonal factors interact to predict a substantial part of burnout in general practice. The most significant risk factors were perceived work-life conflict and poor meaning of work. Policymakers should work to support more sustainable practices based on the specific needs and constraints reported by GPs.

2.
BMJ Open ; 13(6): e073337, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37369427

RESUMEN

INTRODUCTION: Clinical reasoning (CR) is a key competence for physicians and a major source of damaging medical errors. Many strategies have been explored to improve CR quality, most of them based on knowledge enhancement, cognitive debiasing and the use of analytical reasoning. If increasing knowledge and fostering analytical reasoning have shown some positive results, the impact of debiasing is however mixed. Debiasing and promoting analytical reasoning have also been criticised for their lack of pragmatism. Alternative means of increasing CR quality are therefore still needed. Because emotions are known to influence the quality of reasoning in general, we hypothesised that emotional competence (EC) could improve physicians' CR. EC refers to the ability to identify, understand, express, regulate and use emotions. The influence of EC on CR remains unclear. This article presents a scoping review protocol, the aim of which will be to describe the current state of knowledge concerning the influence of EC on physicians' CR, the type of available literature and finally the different methods used to examine the link between EC and CR. METHOD AND ANALYSIS: The population of interest is physicians and medical students. EC will be explored according to the model of Mikolajczak et al, describing five major components of EC (identify, understand, express, regulate and use emotions). The concept of CR will include terms related to its processes and outcomes. Context will include real or simulated clinical situations. The search for primary sources and reviews will be conducted in MEDLINE (via Ovid), Scopus and PsycINFO. The grey literature will be searched in the references of included articles and in OpenGrey. Study selection and data extraction will be conducted using the Covidence software. Search and inclusion results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review model (PRISMA-ScR). ETHICS AND DISSEMINATION: There are no ethical or safety concerns regarding this review. REGISTRATION DETAILS: OSF Registration DOI: https://doi.org/10.17605/OSF.IO/GM7YD.


Asunto(s)
Médicos , Estudiantes de Medicina , Humanos , Razonamiento Clínico , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Literatura de Revisión como Asunto
3.
Clin Toxicol (Phila) ; 61(5): 370-378, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37183679

RESUMEN

BACKGROUND AND OBJECTIVE: In the European Union, the record of cocaine-related seizures indicates an expanding supply. The purity has also been increasing. The health impact of these trends remains poorly documented, in particular, the changes and clinical manifestations of intoxication in young children. We attempted to evaluate the trend in French pediatric admissions for cocaine intoxication/exposure over an 11-year period (2010-2020). METHODS: A retrospective, national, multicenter, study of a pediatric cohort. All children less than 15 years of age admitted to a tertiary-level pediatric emergency unit for proven cocaine intoxication (compatible symptoms and positive toxicological screening) during the reference period were included. RESULTS: Seventy-four children were included. Forty-six percent were less than 6 years old. Annual admissions increased by a factor of 8 over 11 years (+700%) and 57% of all cases were admitted in the last two years. The main clinical signs were neurologic (59%) followed by cardiovascular symptoms (34%). Twelve patients were transferred to the pediatric intensive care unit. Factors significantly associated with the risk of being transferred to the pediatric intensive care unit were initial admission to the pediatric resuscitation area (P < 0.001), respiratory impairment (P < 0.01), mydriasis (P < 0.01), cardiovascular symptoms (P = 0.014), age of less than 2 years (P = 0.014). Blood and/or urine toxicological screening isolated eighteen other substances besides cocaine in 46 children (66%). CONCLUSION: Children are collateral victims of the changing trends in cocaine availability, use and purity. Admissions of intoxicated children to pediatric emergency departments are more frequent and there is an increase in severe presentations. Therefore, this is a growing public health concern.


Asunto(s)
Cocaína , Niño , Humanos , Preescolar , Estudios Retrospectivos , Convulsiones , Hospitalización , Servicio de Urgencia en Hospital
4.
Rev Med Liege ; 78(2): 65-69, 2023 Feb.
Artículo en Francés | MEDLINE | ID: mdl-36799321

RESUMEN

The aim of this two-stage research was to document the stressors and resources experienced by front-line professional groups at the heart of the health crisis due to COVID-19, as well as to bring out of a multidisciplinary reflection, a series of priority proposals for strengthening the care system. Our results highlighted great interprofessional similarities in terms of negative and positive experiences (e.g., feeling of powerlessness, support among colleagues), as well as professional specificities (e.g., the painful feeling of being «alone at the front¼ among nurses). Although the stress, fatigue and/or lassitude factors cited by the participants were more numerous than the protective factors, several participants experienced an opportunity for personal and professional development. Overall, this research found that all front-line professionals have a role to play in improving and building resilience in the system, and that this role could be most effective if played in a context of increased multidisciplinary coordination and communication.


Cette recherche en deux étapes avait pour but de documenter les stresseurs et les ressources expérimentés par les groupes professionnels de la première ligne au cœur de la crise sanitaire liée à la COVID-19, ainsi que de faire émerger, d'une réflexion pluridisciplinaire, une série de propositions prioritaires pour le renforcement du système de soins. Nos résultats ont mis en lumière de grandes similitudes interprofessionnelles en termes de vécus négatifs et positifs (par exemple, le sentiment d'impuissance, le soutien entre collègues), ainsi que des spécificités professionnelles (par exemple, le sentiment douloureux d'être «seules au front¼ chez les infirmières). Bien que les facteurs de stress, de fatigue et/ou de lassitude cités par les participants soient plus nombreux que les facteurs de protection, plusieurs participants ont expérimenté une opportunité de développement personnel et professionnel. De manière générale, il est ressorti de cette recherche que tous les professionnels de la 1ère ligne de soins ont un rôle à jouer dans l'amélioration et la résilience du système, et que ce rôle pourrait être d'autant plus efficace s'il se jouait dans un contexte de coordination et de communication pluridisciplinaire intensifié.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Cuidadores
5.
Sante Publique ; 34(5): 675-682, 2022.
Artículo en Francés | MEDLINE | ID: mdl-36577666

RESUMEN

INTRODUCTION: The COVID-19 health crisis has turned the entire health care system and its actors upside down. For interns in general practice (IMGs), it has changed the way they practice medicine on a daily basis, disrupted their training, and highlighted their social responsibility, a factor that predisposes them to practice general medicine. OBJECTIVE: To assess the impact of the health crisis on the anxiety and motivation for general practice of IMGs. METHOD: Cross-sectional study using an online questionnaire (Qualtrics©) distributed by e-mail to IMGs of two French-speaking Belgian universities between 1 and 31 July 2020 following the first wave of the COVID-19 pandemic. RESULTS: In a sample of 188 IMGs, the following variables, considered as significant risk factor for anxiety, were analyzed: psychological distress prior to the lockdown (OR=2.894), having more than 15 daily telephone consultations during the lockdown (OR=2.724), worrying about being affected by COVID-19 (OR=2.892), or deterioration in quality of life (OR=3.335). Conversely, the feeling of practicing in a supportive environment (OR=0.311) is a protective factor against anxiety. Finally, the feeling of social usefulness reinforces the motivation of IMGs for their profession (OR=4.737). CONCLUSION: This study allowed us to better identify the factors of anxiety and motivation for specialization in general practice among IMGs just after the first wave of COVID-19. Awareness of the risk factors for professional distress and how to deal with them should be considered in the university curriculum.


Introduction: La crise sanitaire du COVID-19 a ébranlé l'ensemble du système de soins de santé et des acteurs qui le constitue. Pour les internes en médecine générale (IMG), celle-ci a modifié l'exercice de la pratique médicale quotidienne, perturbé leur formation et mis en exergue leur responsabilité sociale, l'un des facteurs prédisposant à exercer la médecine générale. Objectif: Évaluer l'impact de la crise sanitaire sur l'anxiété et la motivation pour la médecine générale des IMG. Méthode: Étude transversale réalisée par le biais d'un questionnaire en ligne (Qualtrics©) distribué par courrier électronique aux IMG de deux universités belges francophones, entre le 1er et le 31 juillet 2020, à la suite de la première vague de la pandémie du COVID-19. Résultats: Dans un échantillon de 188 IMG, les variables suivantes ont été analysées : la détresse psychologique préalable au confinement (OR=2,894), réaliser plus de 15 consultations téléphoniques journalières durant le confinement (OR=2,724), l'inquiétude d'être affecté par la COVID-19 (OR=2,892) ou la dégradation de la qualité de vie (OR=3,335), agissent comme des facteurs de risque significatifs de l'anxiété. A contrario, le sentiment de pratiquer dans un environnement soutenant (OR=0,311) est un facteur protecteur de l'anxiété. Enfin, le sentiment d'utilité sociale renforce la motivation des IMG pour leur métier de médecin généraliste (OR=4,737). Conclusion: Cette étude a permis de mieux identifier certains facteurs contributifs d'anxiété parmi les IMG et d'évaluer leur motivation pour la spécialisation en médecine générale après la première vague du COVID-19. Une sensibilisation aux facteurs de risque de la détresse professionnelle et aux ressources à déployer pour y faire face devrait être intégrée au programme des facultés.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Motivación , Calidad de Vida , Estudios Transversales , Pandemias , Control de Enfermedades Transmisibles , Ansiedad/epidemiología , Medicina Familiar y Comunitaria
6.
Soins Pediatr Pueric ; 42(322): 16-17, 2021.
Artículo en Francés | MEDLINE | ID: mdl-34489073

RESUMEN

In July 2017, the French National Authority for Health published a recommendation for good practice specific to shaken baby syndrome specifying the diagnostic approach, the mechanisms involved in shaking and the date of injury. This recommendation details the legal aspects in the case of a diagnosis of non-accidental head trauma, as well as the procedure to follow to report these situations. The High Authority for Health reaffirms this recommendation in December 2019, insisting on the importance of the role of carers in the identification, diagnosis and prevention of these situations.


Asunto(s)
Maltrato a los Niños , Síndrome del Bebé Sacudido , Niño , Maltrato a los Niños/diagnóstico , Humanos , Lactante , Síndrome del Bebé Sacudido/diagnóstico
7.
Soins Pediatr Pueric ; 42(322): 10-15, 2021.
Artículo en Francés | MEDLINE | ID: mdl-34489072

RESUMEN

The baby victim of a shock is not always diagnosed at the time of his first visit to the emergency room. The recommendation for good practice in situations of shaken baby syndrome, published in July 2017 by the French National Authority for Health, helps in the diagnosis and management of these infants by health care providers. When this diagnosis is made, the baby's care pathway is generally long and punctuated by multiple examinations.


Asunto(s)
Maltrato a los Niños , Síndrome del Bebé Sacudido , Niño , Maltrato a los Niños/diagnóstico , Maltrato a los Niños/terapia , Servicio de Urgencia en Hospital , Hospitales , Humanos , Lactante , Síndrome del Bebé Sacudido/diagnóstico , Síndrome del Bebé Sacudido/terapia
8.
Eur J Gen Pract ; 27(1): 111-118, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34132619

RESUMEN

BACKGROUND: Several European countries face a shortage of general practitioners (GPs), in part due to GP attrition. Most studies of GP attrition have focussed on why GPs decide to leave. Yet understanding why GPs decide to remain may also elicit potential interventions to reduce attrition. OBJECTIVES: This study examined GP graduates' career trajectories and underlying decisions to elucidate the factors influencing GP attrition. METHODS: We conducted semi-structured interviews of early to mid-career general practice graduates having completed training in Belgian French-speaking universities between 1999 and 2013. We sampled participants from three categories: full-time GPs, part-time GPs, no longer working as GPs. We analysed each participant's career trajectory and broke it down into major phases. We performed thematic analysis of the factors influencing participants' trajectories. We compared and contrasted trajectories to develop a typology of career trajectories. RESULTS: We identified six types of career trajectories: 'stable' (never considered leaving general practice), 'reaffirmed' (had considered leaving but made substantial changes whilst remaining), 'reactional reorientations' (had left to escape the challenges of general practice), 'inspired reorientations' (had left to pursue a different job), 'reorientations out of loyalty' (had never wanted to practice as GPs and had remained true to their original professional aspirations) and 'mobiles' (valued change and did not want to set-up practice). CONCLUSION: Reasons GPs leave the profession are multiple. The typology that emerged indicates that only some of the career trajectories would benefit from interventions to reduce attrition such as improving working conditions and providing psychological support for GPs.


Asunto(s)
Medicina General , Médicos Generales , Actitud del Personal de Salud , Bélgica , Selección de Profesión , Europa (Continente) , Medicina Familiar y Comunitaria , Humanos , Entrevistas como Asunto
9.
Pediatrics ; 140(3)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28808073

RESUMEN

BACKGROUND AND OBJECTIVES: In France, cannabis consumption is illegal. The health impact of its increasing use and higher tetrahydrocannabinol (THC) concentrations is still poorly documented, particularly that of unintentional pediatric intoxications. We sought to evaluate the French national trend of admissions for unintentional cannabis intoxication in children over an 11-year period (2004-2014). METHODS: A retrospective, national, multicenter, observational study of a pediatric cohort. All children aged <6 years admitted to a tertiary-level pediatric emergency department (PED) for proven cannabis intoxication (compatible symptoms and positive toxicological screening results) during the reference period were included. RESULTS: Twenty-four PEDs participated in our study; 235 children were included, and 71% of the patients were 18 months old or younger. Annual admissions increased by a factor of 13. Hashish resin was the main form ingested (72%). During the study period, the evolution was characterized by a national increase in intoxications, younger intoxicated children (1.28 ± 0.4 vs 1.7 ± 0.7 years, P = .005), and more comas (n = 38) (P = .05, odds ratio 3.5 [1.02-11.8]). Compared with other intoxications, other PED admissions, and the same age population, cannabis-related admissions were greater. There was a potential link between the increased incidence of comas and increased THC concentration in resin seized in France over the period. CONCLUSIONS: Children are collateral victims of changing trends in cannabis use and a prevailing THC concentration. Intoxicated children are more frequent, are younger, and have intoxications that are more severe. This raises a real issue of public health.


Asunto(s)
Cannabis/efectos adversos , Hospitalización/estadística & datos numéricos , Abuso de Marihuana/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Niño , Preescolar , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Francia/epidemiología , Humanos , Incidencia , Lactante , Masculino , Estudios Retrospectivos
10.
Curr Pharm Des ; 23(36): 5502-5510, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28641534

RESUMEN

The analysis of hair to detect drugs and drugs of abuse is performed in various contexts, including child protection cases, abstinence control programs, and workplace drug testing. This alternative matrix offers several advantages, such as a large detection window (months) and non-invasive collection. Segmental analysis of multiple hair strands for drugs and metabolites has been widely reported in the literature over the past three decades, whereas a review of the literature showed that there are only 26 articles that report the analysis of a single hair. They focus on two approaches: mass spectrometry imaging techniques, which improve the resolution of dating an intoxication or conventional methods, such as gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry (LC-MS/MS). Improved sensitivity of LC-MS/MS techniques allows the evaluation of drug content in segments of a single hair. However, the units used to express the results vary, and depend on the authors. Following a review of the literature, we present a case that illustrates drug analyses both in a strand of hair and a single hair. In this case of exposure of a child to zuclopenthixol (ZPT), the analysis of ZPT in a single segmented hair by LC-MS/MS strengthened the presumption of a single administration.


Asunto(s)
Antipsicóticos/análisis , Clopentixol/análisis , Cabello/química , Cabello/crecimiento & desarrollo , Detección de Abuso de Sustancias/métodos , Antipsicóticos/metabolismo , Preescolar , Clopentixol/metabolismo , Cabello/metabolismo , Humanos , Espectrometría de Masas en Tándem/métodos , Factores de Tiempo
11.
Acta Clin Belg ; 72(6): 399-404, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28317474

RESUMEN

INTRODUCTION: This study described the professional activities of graduates of the Advanced Master of General Practice of the Belgian French-speaking universities from 1999 to 2013 and identified factors influencing their situation. METHODS: Between November 2014 and June 2015, all graduates were asked to complete a questionnaire concerning their professional activities. The first part of the analysis described the respondent's socio-demographic and professional characteristics. The second part aimed at detecting possible factors influencing GPs' professional situation. RESULTS: The main results of the study showed that 78.5% of graduates still worked as GPs and 21.5% left and had another activity. The way graduates worked in General Practice was also highly diverse in terms of both working time and types of activities. Only a minority of them were exclusively performing General Practice (8.5%). 45.8% of GPs worked part-time, and were more commonly women and GPs in group practice. This survey confirmed feminisation of the profession and increasing work in associations. Among factors influencing retention in General Practice, preference for specialising in General Practice at time of graduation in medicine and duration of practice influence retention in practice. CONCLUSION: Our survey put the emphasis on the evolution of practice: job and vocational training planning should not be performed based only on previous generations. There is no one predefined way to practise; the blurred boundaries of General Practice activities do not allow for the drafting of a reference frame that could help workforce planning.


Asunto(s)
Médicos Generales/estadística & datos numéricos , Admisión y Programación de Personal/estadística & datos numéricos , Bélgica , Femenino , Medicina General , Humanos , Masculino , Encuestas y Cuestionarios
12.
J Clin Virol ; 74: 54-6, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26655270

RESUMEN

We report a fatal case of acute gastroenteritis in a child with autism spectrum disorder. Multiple viral coinfections were detected by PCR in the patient's stool and digestive biopsy specimens. As viral detection is not necessarily associated with symptomatic disease, a semi-quantitative approach using cycle treshold values was proposed for the clinical interpretation of PCR. We discuss whether concomitant viral infections could be a risk factor for severe outcome in gastroenteritis cases. Individual risk factors are also addressed.


Asunto(s)
Coinfección/diagnóstico , Coinfección/virología , Gastroenteritis/diagnóstico , Gastroenteritis/virología , Virosis/diagnóstico , Virosis/virología , Virus/aislamiento & purificación , Preescolar , Resultado Fatal , Femenino , Humanos , Virus/clasificación
13.
Presse Med ; 44(6 Pt 1): e211-20, 2015 Jun.
Artículo en Francés | MEDLINE | ID: mdl-25943795

RESUMEN

OBJECTIVES: Published operating models about preventive health care and health promotion in primary care were sought with the aim of (1) compiling a functional inventory; and (2) to formulate working hypotheses for the improvement of clinical practice towards more efficiency and more equity. METHODS: Narrative literature review, using keywords related to the various prevention classes, health promotion, primary care, practice models and health care delivery. The diversity of models led to a multi-criteria analysis. RESULTS: Twelve models were selected. Their characteristics were unevenly distributed. The models, whose authors announce that they apply to prevention, mainly describe approaches that focus on individuals within physician-patient relationship, and take into account practice organization. Some socio-ecological and systems models illustrate health promotion: educational practice, group- or population-based targets, community environment and social determinants of health. There is little room for patients in elaborating the models, as they have little role in health care systems. The definitions of prevention, health promotion and patient education greatly differ from one model to another. DISCUSSION: Little is known about practical implementation of the models; assessment data are scarce. Some elements valued by health promotion could be integrated to health care: empowerment of citizens, addressing community environment; increased involvement in local health professionals' networks; integration of individual and collective approaches within the same health care facilities to address simultaneously individual customization, efficiency and equity objectives. These developments may call for adaptation in vocational training and continuous professional development: communication skills, awareness to public health concepts, and early and longitudinal exposure to community-based learning experiences for students.


Asunto(s)
Promoción de la Salud , Modelos Teóricos , Atención Primaria de Salud , Humanos , Atención Primaria de Salud/normas , Atención Primaria de Salud/tendencias
14.
Blood ; 124(3): 441-4, 2014 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-24904115

RESUMEN

Iron is an essential element required for development and survival of all living organisms. In fetuses, maternofetal iron transfer across the placenta is essential for growth and development. In neonates, efficient intestinal iron absorption is required to scavenge as much iron as possible from the low-iron-content milk. During these periods, efficient iron mobilization is ensured by the downregulation of the iron regulatory hormone hepcidin by as-yet uncharacterized molecular mechanisms. Here we demonstrate that the recently described hepcidin repressor-the serine protease matriptase-2 (encoded by Tmprss6)-is responsible for this repression throughout development, with its deficiency leading to increased hepcidin levels triggering iron deficiency and anemia starting in utero. This result might have implications for a better understanding of iron homeostasis during early development in iron-refractory iron deficiency anemia patients, who present with microcytic anemia caused by hyperhepcidinemia, and of questions about the role of matriptase-2 in human neonates.


Asunto(s)
Hepcidinas/metabolismo , Hierro/metabolismo , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/metabolismo , Anemia Ferropénica/etiología , Animales , Proteína Morfogenética Ósea 6/deficiencia , Proteína Morfogenética Ósea 6/genética , Proteína Morfogenética Ósea 6/metabolismo , Regulación hacia Abajo , Femenino , Feto/metabolismo , Proteínas Ligadas a GPI , Proteína de la Hemocromatosis , Homeostasis , Humanos , Deficiencias de Hierro , Hígado/metabolismo , Masculino , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Embarazo , Serina Endopeptidasas/deficiencia , Serina Endopeptidasas/genética , Transducción de Señal
15.
Development ; 141(4): 816-29, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24496619

RESUMEN

Loss of cochlear hair cells in mammals is currently believed to be permanent, resulting in hearing impairment that affects more than 10% of the population. Here, we developed two genetic strategies to ablate neonatal mouse cochlear hair cells in vivo. Both Pou4f3(DTR/+) and Atoh1-CreER™; ROSA26(DTA/+) alleles allowed selective and inducible hair cell ablation. After hair cell loss was induced at birth, we observed spontaneous regeneration of hair cells. Fate-mapping experiments demonstrated that neighboring supporting cells acquired a hair cell fate, which increased in a basal to apical gradient, averaging over 120 regenerated hair cells per cochlea. The normally mitotically quiescent supporting cells proliferated after hair cell ablation. Concurrent fate mapping and labeling with mitotic tracers showed that regenerated hair cells were derived by both mitotic regeneration and direct transdifferentiation. Over time, regenerated hair cells followed a similar pattern of maturation to normal hair cell development, including the expression of prestin, a terminal differentiation marker of outer hair cells, although many new hair cells eventually died. Hair cell regeneration did not occur when ablation was induced at one week of age. Our findings demonstrate that the neonatal mouse cochlea is capable of spontaneous hair cell regeneration after damage in vivo. Thus, future studies on the neonatal cochlea might shed light on the competence of supporting cells to regenerate hair cells and on the factors that promote the survival of newly regenerated hair cells.


Asunto(s)
Animales Recién Nacidos , Transdiferenciación Celular/fisiología , Células Ciliadas Auditivas/fisiología , Regeneración/fisiología , Animales , Proteínas de Transporte de Anión/metabolismo , Células Ciliadas Auditivas/ultraestructura , Ratones , Microscopía Electrónica de Rastreo , Mitosis/fisiología , Transportadores de Sulfato
16.
Soins Pediatr Pueric ; (268): 32-4, 2012.
Artículo en Francés | MEDLINE | ID: mdl-23074804

RESUMEN

Precariousness is a very complex concept that brings together a diverse and fragmented population. The interest in comparing views and opinions is clear for understanding of this phenomenon. A physician in the paediatric emergency unit of a hospital and the head of a "Medecins du Monde" branch evoke the different faces of precariousness. A difficult and sometimes poignant reality, which health care providers must try to cope with.


Asunto(s)
Accesibilidad a los Servicios de Salud , Poblaciones Vulnerables , Niño , Protección a la Infancia , Francia , Humanos , Refugiados
17.
Hum Mutat ; 33(9): 1388-96, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22581667

RESUMEN

Mutations of the TMPRSS6 gene, which encodes Matriptase-2, are responsible for iron-refractory iron-deficiency anemia. Matriptase-2 is a transmembrane protease that downregulates hepcidin expression. We report one frameshift (p.Ala605ProfsX8) and four novel missense mutations (p.Glu114Lys, p.Leu235Pro, p.Tyr418Cys, p.Pro765Ala) found in IRIDA patients. These mutations lead to changes in both the catalytic and noncatalytic domains of Matriptase-2. Analyses of the mutant proteins revealed a reduction of autoactivating cleavage and the loss of N-Boc-Gln-Ala-Arg-p-nitroanilide hydrolysis. This resulted either from a direct modification of the active site or from the lack of the autocatalytic cleavage that transforms the zymogen into an active protease. In a previously described transfection assay measuring the ability of Matriptase-2 to repress the hepcidin gene (HAMP) promoter, all mutants retained some, if not all, of their transcriptional repression activity. This suggests that caution is called for in interpreting the repression assay in assessing the functional relevance of Matriptase-2 substitutions. We propose that Matriptase-2 activity should be measured directly in the cell medium of transfected cells using the chromogenic substrate. This simple test can be used to determine whether a sequence variation leading to an amino acid substitution is functionally relevant or not.


Asunto(s)
Anemia Ferropénica/enzimología , Péptidos Catiónicos Antimicrobianos/metabolismo , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/metabolismo , Serina Proteasas/metabolismo , Transfección/métodos , Adolescente , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Anemia Ferropénica/genética , Péptidos Catiónicos Antimicrobianos/sangre , Péptidos Catiónicos Antimicrobianos/genética , Dominio Catalítico , Niño , Preescolar , Compuestos Cromogénicos/metabolismo , Medios de Cultivo/metabolismo , Activación Enzimática , Pruebas de Enzimas , Precursores Enzimáticos/metabolismo , Mutación del Sistema de Lectura , Silenciador del Gen , Pruebas Genéticas , Células HeLa , Hepcidinas , Humanos , Lactante , Masculino , Proteínas de la Membrana/genética , Datos de Secuencia Molecular , Mutación Missense , Linaje , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Serina Endopeptidasas/genética , Transcripción Genética
18.
Blood ; 117(2): 647-50, 2011 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-20940420

RESUMEN

Hepcidin is the master regulator of iron homeostasis. In the liver, iron-dependent hepcidin activation is regulated through Bmp6 and its membrane receptor hemojuvelin (Hjv), whereas, in response to iron deficiency, hepcidin repression seems to be controlled by a pathway involving the serine protease matriptase-2 (encoded by Tmprss6). To determine the relationship between Bmp6 and matriptase-2 pathways, Tmprss6(-/-) mice (characterized by increased hepcidin levels and anemia) and Bmp6(-/-) mice (exhibiting severe iron overload because of hepcidin deficiency) were intercrossed. We showed that loss of Bmp6 decreased hepcidin levels; increased hepatic iron; and, importantly, corrected hematologic abnormalities in Tmprss6(-/-) mice. This finding suggests that elevated hepcidin levels in patients with familial iron-refractory, iron-deficiency anemia are the result of excess signaling through the Bmp6/Hjv pathway.


Asunto(s)
Anemia Ferropénica/metabolismo , Proteína Morfogenética Ósea 6/metabolismo , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/metabolismo , Transducción de Señal/fisiología , Animales , Péptidos Catiónicos Antimicrobianos/metabolismo , Femenino , Hepcidinas , Hierro/metabolismo , Hierro de la Dieta/metabolismo , Hígado/metabolismo , Ratones , Ratones Noqueados
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