Gene × environment interactions in schizophrenia: evidence from genetic mouse models

The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.

La recherche internationale en génétique et l’utilisation secondaire des données : entre dissociation et harmonisation

L’étude des polymorphismes et des aspects multifactoriels des déterminants de la santé suscite un engouement majeur envers la recherche populationnelle en génétique et génomique. Cette méthode de recherche requiert cependant la collecte et l’analyse d’un nombre élevé d’échantillons biologiques et de données associées, ce qui stimule le développement des biobanques. Ces biobanques, composées des données personnelles et de santé de milliers de participants, constituent désormais une ressource essentielle permettant l’étude de l’étiologie des maladies complexes et multifactorielles, tout en augmentant la rapidité et la fiabilité des résultats de recherche. Afin d’optimiser l’utilisation de ces ressources, les chercheurs combinent maintenant les informations contenues dans différentes biobanques de manière à créer virtuellement des mégacohortes de sujets. Cependant, tout partage de données à des fins de recherche internationale est dépendant de la possibilité, à la fois légale et éthique, d’utiliser ces données aux fins pressenties. Le droit d’utiliser les données personnelles, médicales et génétiques de participants dans le cadre de recherches internationales est soumis à un ensemble complexe et exhaustif d’exigences légales et éthiques. Cette complexité est exacerbée lorsque les participants sont décédés. Fondée sur une révision de l’interprétation individualiste du concept de consentement éclairé, ainsi qu’une perspective constructiviste des concepts de confiance et d’autonomie, cette thèse se situe au carrefour de la recherche, du droit et de l’éthique, et a pour objectif de proposer un modèle promouvant l’harmonisation éthique et juridique des données aux fins de recherches internationales en génétique.

The differential impact of oxytocin receptor (OXTR) genotypes on the risk of autism spectrum disorder (ASD) and resulting social communication deficits

Background: Autism spectrum disorder (ASD) is multifactorial and is likely the result of complex interactions between multiple environmental and genetic factors. Recently, it has been suggested that each symptom cluster of the disorder, such as poor social communication, may be mediated by different genetic influences. Genes in the oxytocin pathway, which mediates social behaviours in humans, have been studied with single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) being implicated in ASD. This thesis examines the presence of different oxytocin receptor genotypes, and their associations with ASD and resulting social communication deficits. Methods: The relationship between four OXTR variants and ASD was evaluated in 607 ASD simplex (SPX) families. Cases were compared to their unaffected siblings using a conditional logistic approach. Odds ratios and associated 95 percent confidence intervals were obtained. A second sample of 235 individuals with a diagnosis of ASD was examined to evaluate whether these four OXTR variants were associated with social communication scores on the Autism Diagnostic Interview – Revised (ADI-R). Parameter estimates and associated 95 percent confidence intervals were generated using a linear regression approach. Multiple testing issues were addressed using false discovery adjustments. Results: The rs53576 AG genotype was significantly associated with a lower risk of ASD (OR = 0.707, 95% CI: 0.512-0.975). A single genotype (AG) provided by the rs2254298 marker was found to be significantly associated with higher social communication scores (Parameter estimate = 1.833, SE = 0.762, p = 0.0171). This association was also seen in a Caucasian only and mothers as the respondent samples. No association was significant following false discovery rate adjustments. Conclusion: The findings from these studies provide limited support for the role of OXTR SNPs in ASD, especially in social communication skills. The clinical significance of these associations remains unknown, however, it is likely that these associations do not play a role in the severity of symptoms associated with ASD. Rather, they may be important in the appearance of social deficits due to the rs2254298 markers association with enlarged amygdalas.

Análisis de la producción científica de los arquitectos técnicos docentes universitarios en España. 1980-2015. Estudio de revistas indizadas en WOS-SCOPUS-CSIC (ICYT-ISOC)

Se estudia la producción científica de los Arquitectos Técnicos docentes universitarios en España en los últimos 35 años ya que el cambio del título académico al de Grado, el aumento del número de doctores y el desarrollo de una política académica que ha convertido en parámetro especial para medir la calidad de la Universidad la cantidad y calidad de los artículos publicados han propiciado un cambio sustancial en esta área del conocimiento. Se determina la investigación producida a través del análisis de las bases de datos WOS-SCOPUS-CSIC(ICYT-ISOC) y las revistas más utilizadas por esta disciplina y se analiza el número de publicaciones de este colectivo por Universidades y revistas. El estudio llevado a cabo evidencia un cambio sustancial en la producción científica de los arquitectos técnicos en España.

A Central Role for Monocyte-Platelet Interactions in Heart Failure

Heart failure (HF) is an increasingly prevalent and costly multifactorial syndrome with high morbidity and mortality rates. The exact pathophysiological mechanisms leading to the development of HF are not completely understood. Several emerging paradigms implicate cardiometabolic risk factors, inflammation, endothelial dysfunction, myocardial fibrosis, and myocyte dysfunction as key factors in the gradual progression from a healthy state to HF. Inflammation is now a recognized factor in disease progression in HF and a therapeutic target. Furthermore, the monocyte-platelet interaction has been highlighted as an important pathophysiological link between inflammation, thrombosis, endothelial activation, and myocardial malfunction. The contribution of monocytes and platelets to acute cardiovascular injury and acute HF is well established. However, their role and interaction in the pathogenesis of chronic HF are not well understood. In particular, the cross talk between monocytes and platelets in the peripheral circulation and in the vicinity of the vascular wall in the form of monocyte-platelet complexes (MPCs) may be a crucial element, which influences the pathophysiology and progression of chronic heart disease and HF. In this review, we discuss the role of monocytes and platelets as key mediators of cardiovascular inflammation in HF, the mechanisms of cell activation, and the importance of monocyte-platelet interaction and complexes in HF pathogenesis. Finally, we summarize recent information on pharmacological inhibition of inflammation and studies of antithrombotic strategies in the setting of HF that can inform opportunities for future work. We discuss recent data on monocyte-platelet interactions and the potential benefits of therapy directed at MPCs, particularly in the setting of HF with preserved ejection fraction.

The Calreticulin gene and myeloproliferative neoplasms

The Philadelphia negative myeloproliferative neoplasms include polycythaemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Patients with these conditions were mainly thought to harbour JAK2V617F mutations or an Myeloproliferative leukaemia (MPL) substitution. In 2013, two revolutionary studies identified recurrent mutations in a gene that encodes the protein calreticulin (CALR). This mutation was detected in patients with PMF and ET with non-mutated JAK2 or MPL but was absent in patients with PV. The CALR gene encodes the calreticulin protein, which is a multifactorial protein, mainly located in the endoplasmic reticulum in chromosome 19 and regulates calcium homeostasis, chaperones and has also been implicated in multiple cellular processes including cell signalling, regulation of gene expression, cell adhesion, autoimmunity and apoptosis. Somatic 52 bp deletions and recurrent 52 bp insertion mutations in CALR were detected and all resulted in frameshift and clusters in exon 9 of the gene. This review will summarise the current knowledge on the CALR gene and mutation of the gene in pathological conditions and patient phenotypes.

A Standardized Classification for Subdural Hematomas- I

Subdural hematomas are a frequent and highly heterogeneous traumatic disorder, with significant clinical and socioeconomic consequences. In clinical and medicolegal practice, subdural hematomas are classified according to its apparent age, which significantly influences its intrinsic pathogenic behavior, forensic implications, clinical management, and outcome. Although practical, this empirical classification is somewhat arbitrary and scarcely informative, considering the remarkable heterogeneity of this entity. The current research project aims at implementing a comprehensive multifactorial classification of subdural hematomas, allowing a more standardized and coherent assessment and management of this condition. This new method of classification of subdural hematomas takes into account its intrinsic and extrinsic features, using imaging data and histopathological elements, to provide an easily apprehensible and intuitive nomenclature. The proposed classification unifies and organizes all relevant details concerning subdural hematomas, hopefully improving surgical care and forensic systematization.

Gut Microbiota, Probiotics and Diabetes

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes.

Neurociencia, discapacidad intelectual y biopolítica

El autor explica el concepto de biopolítica, introducido por Foucault, como el conjunto de estrategias de poder que desarrolla el Estado para ejercer un control exhaustivo sobre la vida. Considera que la conducta anormal y/o patológica es en buena medida un producto social y un instrumento de poder, y que el poder utiliza la biopolítica para controlar la felicidad de la gente. No puede negarse que la discapacidad intelectual es un trastorno biológico multifactorial. Lo importante no es el trastorno sino lo que hacemos con la persona que viene a este mundo con él: y aquí sí que intervienen, y mucho, las ideologías, las creencias, los prejuicios y demás artefactos sociales. Pero no es lícito introducir sospechas sobre la neurociencia “a priori” cuando ésta aborda la realidad de la discapacidad. Y por eso, desde la Bioética debemos estar atentos a qué Bioderecho se promulga y de qué manera tratan nuestras autoridades a estas personas (Biopolítica). La Convención de Derechos de las Personas con Discapacidad es un magnífico ejemplo de cuanto el autor expone, porque detrás de ella hay una profunda reflexión bioética, un adecuado ejercicio biopolítico que finalmente fraguaron en un valioso instrumento jurídico.

Síndrome de Burnout : um estudo com guias de turismo regional em Natal-RN

Burnout is a psychological syndrome triggered in response to continuous exposure to interpersonal stressors. It is considered a multifactorial construct, which is commonly characterized by three dimensions: emotional exhaustion, dehumanization, and lack of personal accomplishment.This study aimed to verify if the three characteristics of burnout (exhaustion, lack of dehumanization and personal accomplishment) are present in people working as guides Tourism in Natal - RN. It is a descriptive and quantitative study. 109 subjects were surveyed. Data collection was done through the use of questionnaires, the instrument used was the characterization of the Burnout Scale (ECB) created and validated in Brazil by Trocoli and Tamayo (2000). In order to analyze data we used descriptive statistics, analysis of core measures, exploratory and confirmatory factor analysis, reliability analysis, cluster analysis, multiple discriminant and Spearman correlation. Factor analysis identified four factors that explain 58.3% of the total variance. Those factors were named exhaustion, deception, avoidance, and dehumanization. The reliability of the instrument, as measured by Cronbach's Alpha was 0.918, which is considered excellent reliability. The 109 subjects were grouped into three cluster, which had the deception, avoidance, and dehumanization as discriminant. It is possible to conclude that the characteristics of burnout syndrome are present in the studied population where 19 people are on the high level of burnout, moderate in 32 and 56 in the light. The correlations between socio-demographic variables studied and the dimensions of burnout, were few and weak. The variable leave for health reasons in the study appeared to be related to feelings of exhaustion and avoidance behavior appeared related to younger individuals and who work only in the activity of Receptive Tourism Guide. Verification of the incidence of burnout in individuals surveyed suggest the need to adopt intervention strategies are individual, organizational and / or combined

In-vitro Clot Formation and Failure

Thesis (Master's)--University of Washington, 2016-08

A alexitimia na categorização de emoções em expressões faciais dinâmicas

A alexitimia é o termo usado para caracterizar as pessoas com défices no processamento, na compreensão e na descrição de emoções. Definida também como um traço de personalidade multifatorial, a alexitimia tem uma prevalência de 10% na população em geral e está associada a uma menor qualidade de vida. Apesar de este estudo incidir-se numa população saudável, a alexitimia está frequentemente associada a patologias físicas e perturbações mentais. O objetivo deste estudo consistiu em verificar a influência da alexitimia na categorização das expressões faciais emocionais, numa tarefa de apresentação de faces dinâmicas. 87 participantes com diferentes índices de alexitimia completaram uma tarefa que consistia na apresentação de faces dinâmicas cujo o intuito era categorizar as expressões faciais de raiva, nojo e alegria. A precisão das respostas e os níveis de intensidade emocional foram manipulados. Os resultados indicaram que os indivíduos, no geral, identificaram mais precisamente e com menores níveis de intensidade emocional a expressão de alegria comparativamente com as expressões negativas (raiva e nojo). Verificou-se também diferenças significativas entre a alexitimia e as expressões faciais emocionais relativamente à precisão na categorização. Deste modo, foi possível verificar neste estudo, que indivíduos com altos níveis de alexitimia foram significativamente menos precisos na identificação da expressão facial de raiva comparativamente com indivíduos com baixos níveis de alexitimia.

Saúde oral e cuidados primários em Odontopediatria

Introdução: A cárie dentária é uma doença multifatorial, infeciosa, transmissível e dependente da dieta, que provoca a desmineralização das estruturas dentárias. Devido a esta natureza etiológica multifatorial é fundamental o aumento da sensibilização e educação das crianças e pais, quer por profissionais de saúde, quer pelos professores em ambiente escolar. A aquisição de hábitos de higiene oral e nutricionais adequados pela criança é um fator imperativo para a manutenção de uma boa saúde oral. Objetivos: Avaliação da Saúde Oral e cuidados primários num grupo de crianças e adolescentes pertencentes ao Agrupamento de Escolas de Alijó. Método: A amostra é constituída por 216 alunos do Agrupamento de Escolas de Alijó, agrupados em três escalões etários: 6-9 anos, 10-14 anos e 15-16 anos. Foi realizada uma observação oral com base no índice de higiene oral simplificado e no índice de cárie (CPOd/cpod- Dentes Cariados, Perdidos e Obturados). Após esta observação foi aplicado um questionário escrito sobre diversos temas relacionados com a saúde oral. Resultados: A percentagem de crianças livres de lesões cariosas aos 6, 12 e 15 anos foi de 33,3%, 28,4% e 16,2%, respetivamente. Os valores da média de número de escovagens diárias aumentam de acordo com a faixa etária. O número de escovagens médias aos 6-9anos, 10-14anos e 15-16anos foi 1,37; 1,48 e 1,55 no sexo masculino, no caso de sexo feminino estes valores passam para 1,58; 1,80 e 1,89 respetivamente. Discussão: Os números registados no presente estudo são semelhantes aos do I Estudo Nacional de Prevalência da Cárie Dentária, onde se verificou percentagens de 33%, 27% e 18,9% para os escalões referentes aos 6 anos, 9 anos e 15 anos. Existe uma melhoria significativa em cada um destes escalões nos dois estudos seguintes realizados pela DGS. Em 2008 estas percentagens foram de 51%, 44% e 28%, respetivamente para cada um dos escalões. Em 2015 existiu apenas um pequeno acréscimo, com percentagens registadas de 54,8%, 53% e 32,4%, respetivamente. A última percentagem, de 32,4%, refere-se neste caso ao escalão dos 18 anos, uma vez que a DGS substituiu o escalão de estudo dos 15 anos de idade. Quando nos referimos ao número de escovagens médio, os números registados neste estudo têm uma evolução semelhante aos encontrados no III Estudo Nacional de Prevalência da Cárie Dentária, publicado em 2015 pela DGS, que refere que aos 6 anos 53% dos inquiridos escova duas vezes ao dia e 25,7% apenas uma vez, enquanto que aos 12 anos nos deparamos com uma descida para 19,9% dos que escovam 1x por dia e um aumento para 69,9% dos que escovam duas vezes. O mesmo estudo afirma ainda que as jovens escovam mais vezes os dentes, tal como no presente estudo. Conclusão: Os últimos anos têm-se revelado determinantes na melhoria da Saúde Oral dos portugueses e a aposta na prevenção, nomeadamente nos Cuidados Primários de Saúde Oral tem apresentado uma mais-valia inquestionável. Como em todos os percursos que se iniciam, a monitorização dos resultados e a sua melhoria contínua podem conduzir à otimização das estratégias e no seu conjunto contribuir para fazer ainda mais e melhor. Este estudo permitiu aferir, que a realidade, em contextos de Saúde Oral, no Concelho de Alijó é preocupante sugerindo que existem assimetrias em Portugal e cabe a todos os intervenientes em Saúde Oral diminuí-las. O envolvimento de cada Médico Dentista neste processo é fundamental.

Évaluation du contrôle sensorimoteur chez les patients ayant une scoliose idiopathique de l'adolescent - Vers un biomarqueur des troubles sensorimoteur basé sur la stimulation vestibulaire galvanique

La scoliose est la pathologie déformante du rachis la plus courante de l’adolescence. Dans 80 % des cas, elle est idiopathique, signifiant qu’aucune cause n’a été associée. Les scolioses idiopathiques répondent à un modèle multifactoriel incluant des facteurs génétiques, environnementaux, neurologiques, hormonaux, biomécaniques et de croissance squelettique. Comme hypothèse neurologique, une anomalie vestibulaire provoquerait une asymétrie d’activation des voies vestibulospinales et des muscles paravertébraux commandés par cette voie, engendrant la déformation scoliotique. Certains modèles animaux permettent de reproduire ce mécanisme. De plus, des anomalies liées au système vestibulaire, comme des troubles de l’équilibre, sont observées chez les patients avec une scoliose. La stimulation vestibulaire galvanique permet d’explorer le contrôle sensorimoteur de l’équilibre puisqu’elle permet d’altérer les afférences vestibulaires. L’objectif de cette thèse est d’explorer le contrôle sensorimoteur en évaluant la réaction posturale provoquée par cette stimulation chez les patients et les participants contrôle. Dans la première étude, les patients sont plus déstabilisés que les contrôles et il n’y a pas de lien entre l’ampleur de l’instabilité et la sévérité de la scoliose. Dans la deuxième étude, à l’aide d’un modèle neuromécanique, un poids plus grand aux signaux vestibulaires a été attribué aux patients. Dans la troisième étude, un problème sensorimoteur est également observé chez les jeunes adultes ayant une scoliose, excluant ainsi que le problème soit dû à la maturation du système nerveux. Dans une étude subséquente, des patients opérés pour réduire leur déformation du rachis, montrent également une réaction posturale de plus grande amplitude à la stimulation comparativement à des participants contrôle. Ces résultats suggèrent que l’anomalie sensorimotrice ne serait pas secondaire à la déformation. Finalement, un algorithme a été développé pour identifier les patients ayant un problème sensorimoteur. Les patients montrant un contrôle sensorimoteur anormal ont également une réponse vestibulomotrice plus grande et attribuent plus de poids aux informations vestibulaires. Globalement, les résultats de cette thèse montrent qu’un déficit sensorimoteur expliquerait l’apparition de la scoliose mais pas sa progression. Le dysfonctionnement sensorimoteur n’est pas présent chez tous les patients. L’algorithme permettant une classification de la performance sensorimotrice pourrait être utile pour de futures études cliniques.

Relación de los estilos de liderazgo en el desempeño de la administración de las IPS hospitalarias de II y III nivel de complejidad de la ciudad de Manizales.

El liderazgo ha sido sujeto de varios estudios, confrontaciones y equivocaciones que lo han conllevado a múltiples y subjetivas interpretaciones y por consiguiente disparidad de actuaciones, siendo el sector salud no ajeno a esta situación. Sin embargo, no se discute la importancia que este conlleva en el actuar a nivel laboral y su influencia y/o relación con los resultados y objetivos organizacionales. Es por ello que esta investigación de corte cuantitativo se diseñó para identificar la relación de los estilos de liderazgo y el desempeño administrativo, siendo enfocado principalmente en los altos y medios directivos pues son estos los responsables de la obtención y mantenimiento de óptimos resultados para la sostenibilidad empresarial. Con el objetivo de identificar la relación específica de los estilos de liderazgo con el desempeño administrativo, el presente estudio se acogió a los indicadores de desempeño definidos por Bass y Avolio (Esfuerzo Extra, Satisfacción y Eficacia del Líder) aplicando por consiguiente el cuestionario Multifactorial de Liderazgo (MLQ) adaptado por Vega, Villa & Zavala, Villalón, siendo éste no solo uno de los instrumentos mas utilizados y estandarizados para el estudio del liderazgo, sino que también permite analizar la frecuencia de su uso, la primacía de cada estilo de liderazgo y especialmente y con objeto del presente estudio, la identificación subyacente del estilo de liderazgo de Rango Completo o Total. El presente cuestionario fue aplicada de forma presencial a los Gerentes Generales, Directores Médicos, Directores Científicos, Directores Administrativos y principales personas a cargo de las IPS hospitalarias de II y III nivel de complejidad de la ciudad de Manizales. En un principio se encontró que el estilo de liderazgo como variable principal mas utilizado por los altos y medios directivos de las IPS hospitalarias de II y III nivel de complejidad de la ciudad de Manizales es el Transformacional, seguido por el Pasivo Evasivo con su comportamiento Dirección por Excepción Activa y por último el Liderazgo Transaccional. Sin embargo no se encontró relación alguna entre los estilos de liderazgo como variables primarias con los indicadores de desempeño, comprobando por último que el Liderazgo de Rango Completo o Total es el estilo de liderazgo que tiene relación directa y positiva con los indicadores de desempeño Esfuerzo Extra, Satisfacción y Eficacia del Líder. Lo anterior permitió no solo apoyar la premisa relacionada con la importancia del liderazgo en toda organización, sino también considerar la importancia de ampliar el estudio incluyendo factores de causalidad que han determinado e influido en la aparición del los estilos de liderazgo.