Inverse association between negative symptoms and body mass index in chronic schizophrenia.

BACKGROUND: We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS: 62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS: Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels

Búsqueda De Nuevos Biomarcadores De La Cognición En Esquizofrenia

ResumenLa búsqueda de biomarcadores en la cognición ha centrado una gran parte de las investigaciones en pacientes con esquizofrenia. La literatura científica es heterogénea y son escasos los estudios disponibles que permitan establecer un modelo integrador de la etiopatogenia y respuesta terapéutica basada en estos marcadores. En el presente trabajo nos proponemos revisar tres aspectos fundamentales correlacionados con el rendimiento cognitivo: 1) la relación entre cognición e inflamación en esquizofrenia, 2) el papel de la prolactina en la cognición, y 3) la asociación entre cognición y factores neurotróficos, en particular el BDNF.Numerosos estudios apoyan la asociación de diversos marcadores inflamatorios con el estado cognitivo en esquizofrenia. El desarrollo de terapias eficaces en el rendimiento cognitivo se ha centrado en las últimas décadas en la búsqueda de fármacos inmunomoduladores o antiinflamatorios. Por otro lado, se ha demostrado la implicación de la prolactina y su función en la cognición y transición a la psicosis, así como en el pronóstico y diagnóstico de la esquizofrenia con independencia del tratamiento antipsicótico. En cuanto a factores neurotróficos, un estudio reciente correlaciona los niveles de BDNF con la mejoría cognitiva en pacientes diagnosticados de esquizofrenia tratados con rehabilitación cognitiva. Concluimos que, a pesar de la diversidad de biomarcadores asociados con el estado cognitivo en esquizofrenia, el BDNF es el biomarcador que acumula mayor evidencia en la literatura científica actual

Association of birth weight and the development of antipsychotic induced adiposity in individuals with treatment resistant schizophrenia.

Though weight gain is a common side effect of antipsychotic treatment, there are no useful predictors of which patients are likely to be affected and to what degree. It has been shown that exposure to adverse conditions during intra-uterine life confers a vulnerability to the development of later life metabolic complications and low birth weight for gestational age has been shown to be a robust marker of such prenatal adversity. We hypothesised that patients with schizophrenia with a lower birth weight will have increased vulnerability to the weight inducing effects of antipsychotic treatment. The relationship between birth weight and total and central adiposity, measured as body mass index (BMI) and waist-to-hip ratio (WHR) respectively, was examined in three groups: drug naïve first episode of psychosis (FEP) patients (n=41), treatment resistant schizophrenia (TRS) patients (n=42) and matched healthy volunteers (n=72). All analyses were controlled for age, gender and duration of treatment exposure. We found that a lower birth weight was associated with higher BMI and WHR only in TRS patients but not in FEP or controls, suggesting that prenatal adversity, as indicated by the surrogate marker of a lower birth weight, confers an increased vulnerability to clozapine induced weight gain.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.euroneuro.2016.03.00

Obstetric Phenotypes in the Heterogeneity of Schizophrenia.

Schizophrenia is a complex mental disorder with genetic and environmental components. Obstetric complications (OCs) are one of the most common environmental risk factors described. However, despite being different in timing and outcome, OCs are usually described as a homogeneous entity. In the present study, we evaluate the presence of different patterns of OCs evaluated with the Lewis-Murray Scale in chronic schizophrenia patients (n = 101) and their association with a crude marker of the intrauterine environment such as weight at birth.OCs related with abnormal fetal growth (p < 0.001) and OCs during gestation (p = 0.003) were associated with lower birth weight. However, difficulties in delivery, complications in pregnancy, and OCs all together (as a set) were not associated with weight at birth.Our results infer that OCs cannot be taken as a homogeneous group. Different patterns of OCs result in different birth weights, which is associated with specific metabolic, cognitive, and brain structure outcomes.This work was supported by the Government of Catalonia, Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2014SGR441), with the grants FI-DGR-2013 Contract of the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2015 FI_B2 00100) and from Fundació Bosch Gimpera (FBG) within the RETOS COLABORACIÓN 2015, funded by the Spanish Ministry of Economic Affairs and Competitiveness (RTC-2015-3440-1) to G. Mezquida. Dr. Bernardo has been supported by research funding from the Spanish Ministry of Health, the Spanish Ministry of Science and Education, the Spanish Ministry of Economic Affairs and Competitiveness, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), by Secretaria d'Universitat i Recerca del Departament d'Economia I Coneixement (2014SGR441), Foundation European Group for Research In Schizophrenia (EGRIS), and the 7th Framework Program of the European Union. Dr. Garcia-Rizo is supported by the PI14/00753 project, integrated into the State Plan of Scientific and Technical Research and Innovation 2013–2016 and co-financed by the ISCIII-General Evaluation Branch and the European Regional Development Fund (ERDF). Dr. Bobes is supported by the Spanish Ministry of Health, the Spanish Ministry of Science and Education, the Spanish Ministry of Economic Affairs and Competitiveness and CIBERSAM. Dr. Paz-Portilla has been also supported by the European Commission, ISCIII-General Evaluation Branch and CIBERSAM. Dr. Savulich is funded by a grant from Eton College and theWallitt Foundation. Dr. Fernanez-Egea is supported, in part, by the NIRH-Biomedical Research Center, Cambridge

Structural Basis for a Munc13–1 Homodimer to Munc13–1/RIM Heterodimer Switch

C (2) domains are well characterized as Ca (2+)/phospholipid-binding modules, but little is known about how they mediate protein–protein interactions. In neurons, a Munc13–1 C (2)A-domain/RIM zinc-finger domain (ZF) heterodimer couples synaptic vesicle priming to presynaptic plasticity. We now show that the Munc13–1 C (2)A domain homodimerizes, and that homodimerization competes with Munc13–1/RIM heterodimerization. X-ray diffraction studies guided by nuclear magnetic resonance (NMR) experiments reveal the crystal structures of the Munc13–1 C (2)A-domain homodimer and the Munc13–1 C (2)A-domain/RIM ZF heterodimer at 1.44 Å and 1.78 Å resolution, respectively. The C (2)A domain adopts a β-sandwich structure with a four-stranded concave side that mediates homodimerization, leading to the formation of an eight-stranded β-barrel. In contrast, heterodimerization involves the bottom tip of the C (2)A-domain β-sandwich and a C-terminal α-helical extension, which wrap around the RIM ZF domain. Our results describe the structural basis for a Munc13–1 homodimer–Munc13–1/RIM heterodimer switch that may be crucial for vesicle priming and presynaptic plasticity, uncovering at the same time an unexpected versatility of C (2) domains as protein–protein interaction modules, and illustrating the power of combining NMR spectroscopy and X-ray crystallography to study protein complexes

Influence of Three Dental Implant Surfaces on Cell Viability and Bone Behavior. An In Vitro and a Histometric Study in a Rabbit Model

The chemical composition and the surface characteristics of dental implants are factors that have a decisive effect on the osseointegration process. The surface characterization at the compositional and topographic level of three dental implants available in the market was performed with different surface treatments: (1) sandblasted and acid etched surface (SLA), (2) hydroxyapatite (HA) and tricalcium phosphate (TCP) blasted surface (HA/TCP), and (3) HA-blasted and non-etching acid washed surface (HA + AW). In addition, an in vitro viability study of MG-63 osteoblast cells was performed with a JC-1 test. To complete the study, an in vivo study was conducted in New Zealand rabbits. The study analyzed the histometric characteristics of the bone formed around the implants at the level of area, volume, bone density, accumulated bone density, and bone–implant contact (BIC). The rabbits were sacrificed at 6 weeks after implants were placed in the tibial metaphysis. No statistically significant differences were observed at the level of cell viability or histometric parameters between the different study groups (p > 0.05). SLA and HA/TCP surfaces were the ones that obtained a higher BIC value. Taking into account the limitations of this study, it can be concluded that the different implant surfaces analyzed favor a good bone response

Investigación en metodologías de aprendizaje para grupos ARA en la materia de arquitectura de computadores

La enseñanza en inglés es uno de los retos a los que se está enfrentando actualmente la universidad española. La Universidad de Alicante ofrece a través de los grupos de Alto Rendimiento Académico (ARA) parte de la docencia de los estudios de grado en inglés. El objetivo principal de esta red es la de consolidar y ampliar la investigación realizada en metodologías de aprendizaje para grupos ARA en la materia de arquitectura de computadores. En consecuencia, se pretende ampliar los materiales docentes en inglés en relación con la enseñanza de asignaturas relacionadas con la materia en estos grupos de alto rendimiento. Estas asignaturas son impartidas por varios miembros de la red en diferentes cursos de los Grados de Ingeniería Informática y de Ingeniería en Sonido e Imagen en Telecomunicación. Como caso práctico, se ha continuado con la investigación en la asignatura Arquitectura de Computadores del Grado de Ingeniería Informática. Para ello, se han elaborado nuevos materiales para prácticas que permiten la participación activa y el trabajo en equipo. Cada uno de los materiales propuestos está diseñado dentro del marco metodológico implementado en la asignatura, relacionado con la consecución de objetivos y competencias, y con la evaluación de la misma

Investigación en metodologías de evaluación de competencias para la materia de arquitectura de computadores

La metodología de evaluación que se aplica en una determinada materia resulta fundamental para el proceso de enseñanza-aprendizaje. Los mecanismos que se utilizan para abordar la tarea de evaluación no sólo sirven para discernir si los estudiantes han alcanzado las competencias mínimas que se plantean en una asignatura. Estos son elementos imprescindibles para establecer la estrategia óptima de enseñanza que pueda adaptarse a los estudiantes. Por otro lado, permite al alumnado ser consciente del aprendizaje que está llevando y motivarlo en este proceso. Sin embargo, la evaluación al cuantificarse puede producir efectos no deseados en el proceso de aprendizaje derivando a que el alumno utilice estrategias que le permitan aprobar una determinada materia sin adquirir plenamente todas las competencias planificadas. El objetivo principal de esta red es la de analizar las metodologías de evaluación de competencias acordes al EEES que permitan establecer sistemas de evaluación que permitan a los estudiantes adquirir competencias de una manera plena. Como caso de estudio, la investigación se centra en la asignatura Arquitectura de Computadores del Grado de Ingeniería Informática de la Universidad de Alicante. Para ello, se analiza en detalle los métodos de evaluación del trabajo en grupo realizando una comparativa con diferentes cursos

Structural and Mutational Analysis of Functional Differentiation between Synaptotagmins-1 and -7

Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis through their C2 domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7). Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 Å resolution. The synaptotagmin-7 C2B domain structure is very similar to that of the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the synaptotagmin-1 C2B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences

Método de evaluación de competencias en Ingeniería. Caso de estudio en Arquitectura de computadores

La evaluación de las competencias adquiridas por los estudiantes a lo largo del curso resulta esencial en el marco del Espacio Europeo de Educación Superior (EEES). El cambio en los procesos de planificación y desarrollo docente ha conllevado un significante ajuste en la evaluación del estudiante en sus aspectos cognitivos, instrumentales y actitudinales. Los nuevos modelos de evaluación han permitido, en general, una mayor realimentación al estudiante, favoreciendo el desarrollo de las competencias específicas y transversales que tiene que adquirir en cada titulación. En este artículo se propone un método de evaluación de competencias que combina la evaluación continua del proceso de adquisición de conocimientos, habilidades y actitudes del alumno junto con la evaluación a partir de un examen final. Se presenta la experiencia en el sistema de evaluación de la materia Arquitectura de los Computadores en la Universidad de Alicante como caso de estudio del método propuesto. Para ello, se analizarán los resultados académicos obtenidos con diferentes sistemas de evaluación desde la implantación de la asignatura en el EEES y se comparará con procesos de evaluación previos al mismo