Evaluation of the integrity of human corneal epithelium maintained in organ-culture during eye banking using Corneamax®

Purpose: Mediums have been developed to conserve corneal endothelium in organ-culture during eye banking. CorneaMax® is used by 25% of Eye Bank in Europe. Only little is known about conservation of corneal epithelium with this medium during banking. Its preservation could be of interest in clinic to cure corneal disease with stem cells deficiency. Therefore, we wanted to examine the integrity of human corneal epithelium maintained in CorneaMax®. Methods: Human corneas, considered unsuitable for transplantation, were obtained from the Eye Bank in Lausanne. Average post-mortem time was 14 hours. Cornoscleral rings were maintained in organ-culture in Corneamax® at 32°C. Samples were formalin-fixed after period ranging from 0 (D0) to 35 days (D35, N=5 for each time points) and stained with H&E. Proliferation and apoptosis were evaluated by immunostaining with antibody against Ki67 and Caspase3 respectively. Results: Corneas, which were not in organ-cultured (D0), showed different morphology, including intact epithelium with 5 to 7 layers, but also completely denuded basement membrane. In two cases, at D0, the epithelium lost its adherence to the basal lamina of the cornea creating a large epithelial sheet. During the two first days, corneas and limbus area lost totally their epithelium, except for some remaining limbal basal cells. From day 2 to day 10, regeneration of the epithelium took place, starting from the limbal region in direction to the central cornea. From day 10 to day 35, corneal epithelium appeared as an atrophic epithelium, consisting of only two cell layers. Proliferation happened in the whole cornea during the 35 days of organ-culture, as shown by Ki67 positive cells. Apoptosis was rarely detected in the corneal epithelium. Conclusions: Corneas maintained in CorneaMax® showed a complete disappearance of the corneal epithelium during the two first days and a conservation of limbal basal cells in the limbal region. These remaining cells allowed a full regeneration of the tissue, leading to an atrophic epithelium, composed of only two cell layers. This atrophic epithelium could be seen in all the organ-cultured corneas during the 35 days of conservation. This study is a first step to develop medium in organ-culture in order to conserve corneal epithelial cells.

Traitement pharmacologique de la schizophrénie : évaluation comparative de la qualité des recommandations de pratique clinique = Comparative evaluation of clinical practice guidelines for the treatment of schizophrenia

De nombreuses recommandations de pratique clinique (RPC) ont été publiées, en réponse au développement du concept de la médecine fondée sur les preuves et comme solution à la difficulté de synthétiser et trier l'abondante littérature médicale. Pour faire un choix parmi le foisonnement de nouvelles RPC, il est primordial d'évaluer leur qualité. Récemment, le premier instrument d'évaluation standardisée de la qualité des RPC, appelé " AGREE " pour appraisal of guidelines for research and evaluation, a été validé. Nous avons comparé - avec l'aide de la grille " AGREE " - les six principales RPC publiées depuis une dizaine d'années sur le traitement de la schizophrénie : (1) les Recommandations de l'Agence nationale pour le développement de l'évaluation médicale (ANDEM) ; (2) The American Psychiatric Association (APA) practice guideline for the treatment of patients with schizophrenia ; (3) The quick reference guide of APA practice guideline for the treatment of patients with schizophrenia [APA - guide rapide de référence] ; (4) The schizophrenia patient outcomes research team (PORT) treatment recommandations ; (5) The Texas medication algorithm project " T-MAP " ; (6) The expert consensus guideline for the treatment of schizophrenia. Les résultats de notre étude ont ensuite été comparés avec ceux d'une étude similaire publiée en 2005 par Gæbel et al. portant sur 24 RPC abordant le traitement de la schizophrénie, réalisée également avec l'aide de la grille " AGREE " et deux évaluateurs [Br J Psychiatry 187 (2005) 248-255]. De manière générale, les scores des deux études ne sont pas trop éloignés et les deux évaluations globales des RPC convergent : chacune des six RPC est perfectible et présente différemment des points faibles et des points forts. La rigueur d'élaboration des six RPC est dans l'ensemble très moyenne, la prise en compte de l'opinion des utilisateurs potentiels est lacunaire et un effort sur la présentation des recommandations faciliterait leur utilisation clinique. L'applicabilité des recommandations est également peu considérée par les auteurs. Globalement, deux RPC se distinguent et peuvent être fortement recommandées selon les critères de la grille " AGREE " : " l'APA - guide rapide de référence " et le " T-MAP ".

Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents.

Dual-energy X-ray absorptiometry (DXA) is the most widely used technical instrument for evaluating bone mineral content (BMC) and density (BMD) in patients of all ages. However, its use in pediatric patients, during growth and development, poses a much more complex problem in terms of both the technical aspects and the interpretation of the results. For the adults population, there is a well-defined term of reference: the peak value of BMD attained by young healthy subjects at the end of skeletal growth. During childhood and adolescence, the comparison can be made only with healthy subjects of the same age, sex and ethnicity, but the situation is compounded by the wide individual variation in the process of skeletal growth (pubertal development, hormone action, body size and bone size). The International Society for Clinical Densitometry (ISCD) organized a Pediatric Position Development Conference to discuss the specific problems of bone densitometry in growing subjects (9-19 years of age) and to provide essential recommendations for its clinical use.

Evaluation et prise en charge des risques de blessure des ischio-jambiers chez le sprinteur

La déchirure des ischio-jambiers est la blessure non-traumatique la plus fréquemment rencontrée dans les sports demandant une course à haute vitesse. Les ischio-jambiers sont particulièrement vulnérables lors de la fin de phase d'oscillation du sprint étant donné qu'ils se contractent excentriquement alors qu'ils sont en position d'allongement. Le renforcement excentrique a été montré comme étant une méthode efficace pour diminuer le risque de blessure. Cependant, les exercices classiquement utilisés comme le Nordic hamstring ne soumettent pas les ischio-jambiers à un niveau d'allongement spécifique au sprint. Dès lors, l'objectif de cette thèse était d'évaluer le fonctionnement des ischio-jambiers à différents niveaux d'allongement musculo- tendineux puis de transposer dans la pratique les résultats obtenus afin de concevoir des exercices plus spécifiques aux besoins des athlètes. Avant cela, une première partie avait pour but de proposer de nouvelles méthodes d'évaluation de terrain des ischio-jambiers. Les différents travaux réalisés pour cette thèse ont permis : 1) de proposer deux nouveaux outils de terrain pour l'évaluation de la flexibilité et de la force des ischio-jambiers ; 2) de montrer que le niveau d'allongement influence directement la force produite par les ischio-jambiers et de suggérer que ce niveau d'allongement semble être un stimulus au moins aussi déterminant que le mode de contraction musculaire pour générer des adaptations de l'architecture musculaire propices à la diminution du risque de blessure ; 3) de proposer des modalités spécifiques de renforcement des ischio-jambiers destinées aux sprinteurs dans une perspective de prévention des blessures et de montrer l'efficacité de ces recommandations sur l'amélioration d'un certain nombre de facteurs de risque de blessure. Finalement, ce travail a ouvert de nouvelles perspectives allant de la proposition d'exercices de renforcement de terrain au développement d'un système motorisé spécifique au sprint permettant le renforcement et l'évaluation de la force des ischio-jambiers en passant par différents projets de recherche. -- High-speed running sports accounts for the majority of hamstring strains. The terminal swing phase of the running cycle is believed to be the most hazardous as the hamstrings are undergoing an active lengthening contraction in a long muscle length position. Prevention-based strength training relies mainly on eccentric exercises. However, most hamstrings exercises like the Nordic hamstring are performed at an inadequately low hip-flexion angle. Thus, the objective of this thesis was to assess the hamstring function at different muscle lengths and depending on the obtained results to design strength exercises more specific to the athlete's need. Before that, a first part of this thesis aimed to develop new assessment methods of the hamstring on site. The different studies included in the present thesis allowed: 1) to propose two new methods to test the hamstring flexibility and strength on the field; 2) to show that the hamstring muscle length directly influences its level of strength, and to suggest that the training range of motion could be a dominant stimulus (as important than contraction type) for modifying the muscle architecture, which leads to a decrease in hamstring injury risk; 3) to define sprint specific parameters for prevention-based strength training, and to show the efficiency of these recommendations on the improvement of several injury risk factors for the hamstring. Finally, this thesis proposed new perspectives: 1) new strength exercises on site; 2) the development of a motorised device specific for the sprint which could be used to strength and to assess the hamstring; 3) several future research projects.

Physico-chemical characterization and oxidative reactivity evaluation of aged brake wear particles

Brake wear dust is a significant component of traffic emissions and has been linked to adverse health effects. Previous research found a strong oxidative stress response in cells exposed to freshly generated brake wear dust. We characterized aged dust collected from passenger vehicles, using microscopy and elemental analyses. Reactive oxygen species (ROS) generation was measured with acellular and cellular assays using 2′7-dichlorodihydrofluorescein dye. Microscopy analyses revealed samples to be heterogeneous particle mixtures with few nanoparticles detected. Several metals, primarily iron and copper, were identified. High oxygen concentrations suggested that the elements were oxidized. ROS were detected in the cell-free fluorescent test, while exposed cells were not dramatically activated by the concentrations used. The fact that aged brake wear samples have lower oxidative stress potential than fresh ones may relate to the highly oxidized or aged state of these particles, as well as their larger size and smaller reactive surface area.

Research and development, where people are exposed to nanomaterials

OBJECTIVES: Many nanomaterials (materials with structures smaller than 100 nm) have chemical, physical and bioactive characteristics of interest for novel applications. Considerable research efforts have been launched in this field. This study aimed to study exposure scenarios commonly encountered in research settings. METHODS: We studied one of the leading Swiss universities and first identified all research units dealing with nanomaterials. After a preliminary evaluation of quantities and process types used, a detailed analysis was conducted in units where more than a few micrograms were used per week. RESULTS: In the investigated laboratories, background levels were usually low and in the range of a few thousand particles per cubic centimeter. Powder applications resulted in concentrations of 10,000 to 100,000 particles/cm(3) when measured inside fume hoods, but there were no or mostly minimal increases in the breathing zone of researchers. Mostly low exposures were observed for activities involving liquid applications. However, centrifugation and lyophilization of nanoparticle-containing solutions resulted in high particle number levels (up to 300,000 particles/cm(3)) in work spaces where researchers did not always wear respiratory protection. No significant increases were found for processes involving nanoparticles bound to surfaces, nor were they found in laboratories that were visualizing properties and structure of small amounts of nanomaterials. CONCLUSIONS: Research activities in modern laboratories equipped with control techniques were associated with minimal releases of nanomaterials into the working space. However, the focus should not only be on processes involving nanopowders but should also be on processes involving nanoparticle-containing liquids, especially if the work involves physical agitation, aerosolization or drying of the liquids.

Uses of cancer registries for public health and clinical research in Europe : results of the European Network of Cancer Registries survey among 161 population-based cancer registries during 2010-2012

AIM: To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area. METHODS: During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage. RESULTS: Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional. CONCLUSION: Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results.

Developing a theoretical framework using a nursing perspective to investigate perceived health in the "Sandwich Generation" group

Coexisting workloads from professional, household and family, and caregiving activities for frail parents expose middle-aged individuals, the so-called "Sandwich Generation", to potential health risks. Current trends suggest that this situation will continue or increase. Thus SG health promotion has become a nursing concern. Most existing research considers coexisting workloads a priori pathogenic. Most studies have examined the association of one, versus two, of these three activities with health. Few studies have used a nursing perspective. This article presents the development of a framework based on a nursing model. We integrated Siegrist's Effort-Reward Imbalance middle-range theory into "Neuman Systems Model". The latter was chosen for its salutogenic orientation, its attention to preventive nursing interventions and the opportunity it provides to simultaneously consider positive and negative perceptions of SG health and SG coexisting workloads. Finally, it facilitated a theoretical identification of health protective factors.

A prospective evaluation of ultrasound as a diagnostic tool in acute microcrystalline arthritis.

INTRODUCTION: The performance of ultrasound (US) in the diagnosis of acute gouty (MSU) arthritis and calcium pyrophosphate (CPP) arthritis is not yet well defined. Most studies evaluated US as the basis for diagnosing crystal arthritis in already diagnosed cases of gout and few prospective studies have been performed. METHODS: One hundred nine consecutive patients who presented an acute arthritis of suspected microcrystalline arthritis were prospectively included. All underwent an US of the symptomatic joints(s) and of knees, ankles and 1(st) metatarsopalangeal (MTP) joints by a rheumatologist "blinded" to the clinical history. 92 also had standard X-rays. Crystal identification was the gold standard. RESULTS: Fifty-one patients had MSU, 28 CPP and 9 had both crystals by microscopic analysis. No crystals were detected in 21. One had septic arthritis. Based on US signs in the symptomatic joint, the sensitivity of US for both gout and CPP was low (60 % for both). In gout, the presence of US signs in the symptomatic joint was highly predictive of the diagnosis (PPV = 92 %). When US diagnosis was based on an examination of multiple joints, the sensitivity for both gout and CPP rose significantly but the specificity and the PPV decreased. In the absence of US signs in all the joints studied, CPP arthritis was unlikely (NPV = 87 %) particularly in patients with no previous crisis (NPV = 94 %). X-ray of the symptomatic joints was confirmed to be not useful in diagnosing gout and was equally sensitive or specific as US in CPP arthritis. CONCLUSIONS: Arthrocenthesis remains the key investigation for the diagnosis of microcrystalline acute arthritis. Although US can help in the diagnostic process, its diagnostic performance is only moderate. US should not be limited to the symptomatic joint. Examination of multiple joints gives a better diagnostic sensitivity but lower specificity.

Translation and psychometric evaluation of a French version of the Readiness for Hospital Discharge Scale.

AIMS AND OBJECTIVES: To evaluate the reliability and the factor structure of the Readiness for Hospital Discharge Scale - French version. BACKGROUND: The patient's perspective is essential when assessing risk for adverse events at hospital discharge. Developed in the USA, the Readiness for Hospital Discharge Scale is the only instrument that measures an individual's self-perception of readiness before leaving the hospital. A French version of the Readiness for Hospital Discharge Scale was developed and validated. DESIGN: Cross-sectional study. METHODS: A convenience sample of 265 older inpatients from four medical units was selected. The translation and cultural adaptation of the scale involved experts in gerontology and the French language and included back translation. The items were semantically evaluated and pretested in 10 older inpatients. The scale's psychometric properties were internally validated by using confirmatory and exploratory factor analyses. Reliability was assessed by examining the internal consistency of its items. RESULTS: Goodness-of-fit indices of the confirmatory factor analyses were not adequate, but reliability was acceptable (Cronbach's α = 0·80). Exploratory factor analysis of the French version provided results close to those described for the English version, with three similar subscales (physical and emotional readiness, coping with medical treatment and personal care), whereas the initially described Expected Support subscale was not identified in the French version. CONCLUSION: The Readiness for Hospital Discharge Scale - French version appears to be partially consistent with its original English version, but requires additional adaptation to fully take into account the Swiss context and culture to achieve its original aim. RELEVANCE TO CLINICAL PRACTICE: Assessing patient readiness for hospital discharge before leaving hospital could help nurses to improve the discharge planning process and achieve better patient preparedness and care coordination.

Evaluation du risque de récidive dans les expertises pénales: quels outils? Quets indicateurs? Quelles pratiques [Risk assessment in forensic psychiatric reports: what kind assessment instrument? What indicator? What practical?].

Here we present results of studies conducted by the Research Unit of Legal Psychiatry and Psychology of Lausanne about risk assessment and protective factors in the evaluation of violence recidivism. It aims to help experts in considering the relevance and use of tools at their disposal. Particular attention is given to the significance of protective factors and impulsive dimensions, as to the inter-raters process that leads to the final deliberations.

Complexity of the Paradigms Present in Quality Criteria of Qualitative Research Grids

With qualitative methods being increasingly used in health science fields, numerous grids proposing criteria to evaluate the quality of this type of research have been produced. Expert evaluators deem that there is a lack of consensual tools to evaluate qualitative research. Based on the review of 133 quality criteria grids for qualitative research in health sciences, the authors present the results of a computerized lexicometric analysis, which confirms the variety of intra- and inter-grid constructions, including within the same field. This variety is linked to the authors' paradigmatic references underlying the criteria proposed. These references seem to be built intuitively, reflecting internal representations of qualitative research, thus making the grids and their criteria hard to compare. Consequently, the consensus on the definitions and the number of criteria becomes problematic. The paradigmatic and theoretical references of the grids should be specified so that users could better assess their contributions and limitations.

Evaluation of molecular, cellular and behavioral consequences of serotonin 1A receptor deletion

In 1998, three different research groups simultaneously reported increased anxiety-related behavior in tests of conflict in their serotonin 1a (5-HT1a) receptor knockout (KO) line with male mice being more severely affected by 5-HT1a receptor deletion than female KO. Similarly, in the hippocampus, we observed increased dendritic complexity in the stratum radiatum of CA1 pyramidal neurons in male but not in female 5-HT1a receptor KO mice. These observations prompted us to investigate gender- dependent differences of 5-HT1a receptor deletion in hippocampal-related behavioral tasks. Testing our mice in anxiety-related paradigms, we reproduced the original studies showing increased anxiety- related behavior in male 5-HT1a receptor KO mice when compared to male WT mice, but no difference between female 5-HT1a receptor KO and WT mice. Similarly, male 5-HT1a receptor KO mice were impaired in association of aversive stimuli fear conditioning paradigms. We argue that increased dendritic complexity and increased synaptic strength of CA3-CA1 synapses in the stratum radiatum impaired proper signal propagation attributed to overactivation of CA1 pyramidal neurons leading to impaired fear memory of male 5-HT1a receptor KO mice. Similar mechanisms in the ventral hippocampus are likely to have contributed to gender-dependent differences in anxiety-related behavior in our and the original studies from 1998. In this study, we started to shed light on the 5-HT1a receptor downstream signaling pathways involved in dendritogenesis of pyramidal neurons during early postnatal development. We could show that NR2B-containing NMDA receptor during development acts downstream of 5-HT1a receptor and is responsible for increased amount of branching in male 5-HT1a receptor KO mice. Conversely, protein and NR2B mRNA expression was increased in 5-HT1a receptor KO mice at P15. Although the exact signaling cascade of 5-HT1a receptor regulating NR2B-containing NMDA receptor has not been determined, CaMKII is a potential downstream effector to influence transportation and removal of NR2B-containing NMDA receptors to and from the synapse. In contrast, Erk1/2 likely acts downstream of NR2B-containing NMDA receptors and was shown to be sufficient to regulate dendritic branching. Moreover, increased NR2B-containing NMDA receptor mediated cell death via excitotoxicity during development and is likely to be involved in reduced survival of adult born neurons in the hippocampus of 5-HT1a receptor KO male. The convergence of 5-HT1a receptor signaling onto NR2B-containing NMDA receptor signaling enables estrogen to interfere with its downstream pathway via G-protein coupled estrogen receptor 1 activation resulting in normalization of branching and behavior in female 5-HT1a receptor mice. In conclusion, our data strongly suggests a hormone- regulated mechanism that by converging on NR2B-containing NMDA receptor signaling is able to normalize morphology of pyramidal neurons and behavior of female 5-HT1a receptor KO mice. Our findings provide a possible explanation for gender-dependent differences in the occurrence of mental disorders with 5-HT1a receptor abnormalities as a strong predisposing factor. -- En 1998, trois équipes de recherche ont décrit un comportement de type anxieux dans des tests de conflit pour leur souris transgéniques avec une délétion du gène pour le récepteur 5-HT1a de la sérotonine. De plus, les trois groupes rapportent un phénotype plus sévère pour le comportement anxieux chez les souris transgéniques mâles que femelles. Dans l'hippocampe, la région avec la densité de récepteur 5-HT1a la plus élevée dans le télencéphale, nous avons observé dans le stratum radiatum une complexité accrue des arborisations dendritiques des neurones pyramidaux du secteur CA1 chez les souris transgénique mâles mais pas chez les femelles. Cette observation nous a encouragés à initier cette étude sur les différences en fonction du genre utilisant les tests comportementaux en rapport avec les fonctions de l'hippocampe chez les souris déficientes pour le récepteur 5-HT1a.Testant nos souris avec des paradigmes associés à l'anxiété, nous avons reproduit les données originales montrant que les souris transgéniques mâles ont un phénotype plus sévère que les souris mâles sauvages, mais qu'aucune différence n'est observée entre les femelles sauvages et transgéniques. De même, les souris mâles déficientes pour le récepteur 5-HT1a sont handicapées dans les tests de conditionnement au stress avec des stimuli aversifs. Nous faisons l'hypothèse que l'augmentation de la complexité de l'arborisation dendritique et l'augmentation de la force du signal synaptique entres les régions CA3 et CA1 de l'hippocampe dans le stratum radiatum perturbe la propagation du signal nerveux qui conduit à l'hyperactivation des neurones du secteur CA1. Ceci conduit à une mémoire de stress altérée chez les souris mâles déficientes pour le récepteur 5-HT1a. Un mécanisme similaire dans l'hippocampe ventral contribue probablement aux différences en fonction du genre dans les tests pour le comportement de type anxieux qui ont été rapportés dans les études originales de 1998. Les mesures de protéine et de mRNA ont mis en évidence une augmentation de l'expression du récepteur NMDA contenant la sous- unité NR2B dans les souris déficientes pour le récepteur 5-HT1a à P15. Dans les cultures organotypiques d'hippocampe, nous avons commencé à disséquer les messagers secondaires à l'activation du récepteur 5-HT1a qui sont impliqués dans la régulation de la croissance dendritique des neurones pyramidaux pendant la période postnatale précoce. Nous avons démontré que les récepteurs NR2B sont en aval de l'activation du récepteur 5-HT1a et qu'ils sont impliqués dans l'accroissement du nombre de dendrites chez la souris mâle déficiente pour le récepteur 5-HT1a. Bien que la cascade de signalisation du récepteur 5-HT1a pour réguler les récepteurs NMDA contenant le NR2B ne soit pas établie, CaMKII est identifié comme un effecteur potentiel pour altérer le transport du récepteur NMDA à la synapse. D'autre part, Erk1/2 est probablement un messager en aval du NR2B du récepteur NMDA, et a été documenté comme suffisant pour réguler l'arborisation dendritique. L'augmentation de NR2B à la synapse des souris déficientes pour le récepteur 5-HT1a peut conduire à une augmentation de l'excitotoxicité dans les cellules. Nous avons observé une augmentation chez la souris déficiente pour le récepteur 5-HT1a de la mort cellulaire dans des tranches d'hippocampe stimulées, ce qui peut être en relation avec la réduction de la survie des neurones générés dans l'hippocampe de la souris mâle transgénique adulte par rapport à la souris mâle sauvage. De plus, la convergence de la signalisation du récepteur 5-HT1a sur la signalisation de la sous-unité NR2B du récepteur NMDA permet à l'oestrogène d'interférer avec sa voie de signalisation du récepteur de l'oestrogène couplé à une protéine G (GPER-1), ceci permettant à l'oestrogène de réduire la taille de l'arborisation des neurones pyramidaux de CA1 chez la femelle de la souris déficiente pour le récepteur 5-HT1a. En conclusion, nos observations suggèrent fortement qu'un mécanisme hormonal convergeant sur la voie de signalisation de la sous-unité NR2B du récepteur NMDA permet la normalisation de l'exubérance des dendrites des neurones CA1 de l'hippocampe et du comportement des souris femelles déficientes pour le récepteur 5-HT1a. Ceci donne une explication possible pour la différence en fonction du genre dans l'apparition de troubles mentaux avec les variations du récepteur 5-HT1a comme facteur de prédisposition important.