Papel de la galectina-3 en la respuesta inmune y en la pérdida neuronal asociada a un modelo murino de daño cerebral traumático.

La lesión cerebral traumática (TBI) es actualmente una causa importante de muerte y discapacidad en la sociedad occidental, con una estimación de 2,5 millones de personas afectadas cada año en Europa, lo que indica la necesidad de establecer nuevos avances orientados a su prevención y tratamiento. Dentro de las primeras 24 horas después del daño se desencadena una respuesta inflamatoria, aumentando la expresión de marcadores inflamatorios, incluyendo la lectina galectina-3 y, asociada a esta neuroinflamación, una pérdida neuronal. En este proyecto de tesis hemos usado un modelo murino de TBI mediante un impacto cortical controlado para estudiar el papel de la galectina-3 en la regulación de la respuesta inmune y neurodegeneración asociada al TBI. Con objeto de dilucidar y distinguir el papel intracelular y extracelular de la galectina-3 utilizamos ratones transgénicos con ausencia total de la galectina-3 (ratones KOGal3) y ratones de fenotipo silvestre (ratones WT) a los que se trató con anticuerpos de neutralización contra galectina-3 (ratones Ac-Gal3) con objeto de inhibir selectivamente esta proteína a nivel extracelular. Nuestro análisis muestra un aumento significativo en la expresión de la galectina-3 en el cerebro a las 24 horas después del impacto y en el lado ipsilateral al daño exclusivamente. En estas condiciones, el grupo celular responsable de esta expresión es la microglía reactiva, la cual se encuentra invadiendo la capa degenerada de células piramidales del hipocampo. Además, detectamos la liberación de la proteína galectina-3 al espacio extracelular y de ahí al líquido cefalorraquídeo, produciéndose también la unión de esta proteína liberada al receptor TLR4. Por otra parte, se observa a corto y largo plazo una pérdida neuronal producida por el TBI en la región ipsilateral de la corteza y el hipocampo, produciéndose, tanto con la ausencia total de la galectina-3 como con la neutralización, un efecto neuroprotector frente al daño neuronal. Además, los análisis realizados sobre la población microglial revelan que la neutralización de la galectina-3 disminuye la activación de estas células y la disminución de la expresión de los marcadores proinflamatorios (IL1β, IL6 y NOS2) inducidos en la región ipsilateral al daño tras el TBI. Por otro lado, la ausencia total de la galectina-3 aumenta la expresión de marcadores antiinflamatorios (ARG1 y Ym1) y la expresión de BDNF, también inducida en la región ipsilateral tras el TBI. Por lo que la inducción de la liberación de la galectina-3 actúa como una señal de alarma en condiciones de TBI e induce una fuerte respuesta proinflamatoria y activación microglial, a través de la activación del receptor TLR4, la cual es responsable de la progresión de la neurodegeneración producida tras el daño inicial del TBI. Además, la galectina-3 extracelular podría interaccionar con el receptor MerTK actuando como opsonina y facilitando la fagocitosis de neuronas por parte de la microglía reactiva, contribuyendo de nuevo a la pérdida neuronal. Por otro lado, parece ser que la galectina-3 intracelular es la responsable de la regulación del estado antiinflamatorio y de la expresión de BDNF inducida por el TBI. Por lo tanto, terapias dirigidas a modular la expresión o disponibilidad de la galectina-3 dentro de las primeras 24 horas después de la lesión podrían tener un efecto potencialmente positivo en los pacientes disminuyendo el avance y secuelas neuronales asociadas y desencadenadas por el daño inicial del TBI.Traumatic brain injury (TBI) is currently a major cause of death and disability in western society, with an estimated 2.5 million people affected each year in Europe, indicating the need to establish new advances aimed at its prevention and treatment. Within the first 24 hours after the damage an inflammatory response is triggered increasing the expression of inflammatory markers, including the lectin galectin-3, and a neuronal loss is also associated with this neuroinflammation. The aim of this thesis project is to study the role of galectin-3 in the regulation of the immune response and neurodegeneration associated with TBI, we have used a TBI model in mice by a controlled cortical impact. In order to elucidate and to distinguish between the intracellular and extracellular role of galectin-3 we used galectin-3 knock out transgenic mice (KOGal3 mice), with total absence of the galectin-3 protein, and wild type mice (WT mice) to which were treated with neutralizing antibodies against galectin-3 (Ac-Gal3 mice) in order to selectively inhibit this protein at the extracellular level. Our results show a significant increase in the expression of galectin-3 in the brain at 24 hours after impact and on the ipsilateral side. Under these conditions, we find that the cellular group responsible for this expression is reactive microglia, which is invading the degenerated layer of pyramidal cells of the hippocampus. In addition, we detected galectin-3 protein release to the extracellular space and, and subsequently from there to the cerebrospinal fluid, producing the binding of this released protein to the TLR4 receptor. A short and long term neuronal loss was observed in the damaged ipsilateral area in the cortex and the hippocampus, producing a neuroprotective effect against the neuronal damage produced by the TBI both with the total absence of galectin-3 and with neutralization. In addition, the analyses performed on the microglial population reveal that the neutralization of galectin-3 decreases the activation of these cells and furthermore, the expression of the proinflammatory markers (IL1β, IL6 and NOS2) induced in the damaged ipsilateral area. On the other hand, the total absence of galectin-3 increases the expression of antiinflammatory markers (ARG1 and Ym1) and the expression of BDNF, also induced in the ipsilateral area by TBI. Thus, the induction of galectin-3 release acts as a warning signal in TBI conditions and induces a strong microglia activation and proinflammatory response, through the activation of the TLR4 receptor, which is responsible of the progression of neurodegeneration produced by the TBI-initial damage. In addition, extracellular galectin-3 could interact with the MerTK receptor acting as an opsonin and facilitating phagocytosis of neurons by mean of the reactive microglia, contributing again to neuronal loss. On the other hand, it seems that intracellular galectin-3 is responsible for the regulation of the antiinflammatory state and the expression of BDNF induced by the TBI. Therefore, therapies focus on modulating the expression or availability of galectin-3 within the first 24 hours after the injury can have potentially a positive effect on TBI-patients by decreasing the advance of TBI-associated neuronal lost

Estudio de prefactibilidad técnico-económico-ambiental para el anteproyecto Vía turística entre los balnearios de San Jorge y el Menco, en el Departamento de Rivas

Este trabajo, el cual ha sido titulado: Estudio de prefactibilidad técnico-económico-ambiental para el anteproyecto Vía Turística entre los balnearios de San Jorge y El Menco, en el departamento de Rivas, se ha presentado como trabajo final para el Seminario de Graduación en la Facultad de Ciencias e Ingenierías de la UNAN-Managua, con el objetivo de que los autores obtengan el título de Ingeniero Civil. Este trabajo ha sido elaborado con mucha dedicación, aplicando los conocimientos adquiridos tanto en las aulas de clase como en las prácticas profesionales, con el fin de que pueda ser utilizado como un suplemento que sirva para guiarse en la realización de un estudio de prefactibilidad en los aspectos teóricos y técnicos referentes al diseño de carreteras. El estudio del anteproyecto se presenta en forma clara y detallada, para que el lector lleve una secuencia lógica de cada uno de los aspectos que encuentre a medida que se va introduciendo en la lectura del mismo. El documento se divide en seis capítulos, en los cuales se detallan todos los estudios: Caracterización del Proyecto, Estudio de Mercado, Estudio Técnico, Evaluación Económica, Análisis Social y Análisis Ambiental. Además se presenta una sección de anexos, en los que se detallan las tablas de referencias de diseño, resumen de resultados, bibliografía empleada, fotos del sitio de estudio y los respectivos planos constructivos. El proyecto cuenta con 22.91 km en su totalidad, requiriendo de una inversión inicial muy alta para los ingresos económicos de nuestro país y de esta forma poder ejecutarlo, por tanto se realizaron los diferentes estudios (Mercado, Técnico, Ambiental) para una primera parte del proyecto (9.22 km) con el fin de realizar el proyecto en varias etapas, de esta manera resultaría más factible para los inversionistas desembolsar el monto total del proyecto por parte, es decir mediante diferentes etapa

La identificación de las demandas sociales y la participación pública en los proyectos de agua y saneamiento en los países en vías de desarrollo: la experiencia de ingeniería sin fronteras

La correcta identificación y priorización de las intervenciones entorno a los servicios de agua y saneamiento en países en vías de desarrollo es uno de los aspectos clave de la cooperación internacional. Constituye, explícitamente, una de las 18 metas de los Objetivos de Desarrollo del Milenio, referente político internacional en los temas de desarrollo y cooperación. En muchos países, además de la escasez del recurso y de los conflictos de prioridad entre distintos usos, destaca el alto porcentaje de personas sin acceso al agua potable y la débil capacidad de regulación e intervención de la administración pública. Por otra parte, las capacidades para el mantenimiento y la gestión son en general limitadas, lo que unido a una capacidad de pago también limitada, hace indispensable que la elección de la tecnología a aplicar, el nivel de servicio y el modelo de gestión sean adecuados al entorno socio-cultural y económico. Esta compleja situación requiere del ingeniero una aproximación flexible y abierta entorno la gestión del ciclo del proyecto así como el conocimiento de herramientas y procedimientos adecuados para la correcta identificación de las demandas sociales y la concertación de todos los agentes implicados. Asimismo, se hace necesario compaginar la dotación de infraestructuras y la capacitación tecnológica con la planificación de inversiones públicas y las acciones de presión política dirigidas al desarrollo de políticas que tengan por objetivo la institucionalización de los servicios básicos y su universalidad, tomando en consideración tanto el esfuerzo inversor del país receptor como la inversión internacional canalizada a través del sistema de cooperación para el desarrollo. En la presente comunicación se detalla la experiencia que a este respecto acumula Ingeniería Sin Fronteras (ISF) en los proyectos que ejecuta en África sub-sahariana y Centroamérica desde mediados de los años 90. Se ilustran, a través de diversos ejemplos, los procesos participativos dinamizados, y se muestran metodologías de intervención que pueden ser aplicadas en otros contextos de escasos recursos.Peer ReviewedPostprint (published version

The Frustration of Novelty and Basic Psychological Needs as Predictors of Maladaptive Outcomes in Physical Education

Background The need for novelty has been recently proposed as a candidate need within basic psychological needs theory (BPNT). In physical education (PE), research has shown that meeting students’ need for novelty is often positively associated with enhanced (and negatively associated with impaired) pupils’ well-being. Frustrating students’ novelty has also been negatively related to achieving multiple positive outcomes in PE. However, no research has explored whether frustration of novelty is positively associated with maladaptive consequences for pupils in this educational context, which is a necessary criterion to be included within BPNT. Purpose In this correlational study, we aimed to determine whether frustration of novelty was associated with up to 10 maladaptive outcomes in a similar way as the frustration of the three basic psychological needs (autonomy, competence, and relatedness). The maladaptive outcomes analyzed were amotivation, boredom, negative affect, entity beliefs, fear of failure, worry, concentration disruption, somatic and social physique anxiety, and oppositional defiance. Research design Cross-sectional study. Methods A total of 533 students (Mage = 14.47, SD = 1.34; 56.66% female) from eight secondary schools completed online questionnaires assessing their basic psychological needs frustration, novelty frustration and diverse maladaptive outcomes in PE. Pearson's correlations and hierarchical regression analyses controlling by sex, age, and race, were calculated to test the associations among these variables. Findings The correlation coefficients for novelty frustration were like those found for the three basic psychological needs concerning maladaptive outcomes in PE students. Particularly, hierarchical regression analyses showed that frustrating novelty in PE predicted amotivation (β = .11, p = .039), boredom (β = .23, p < .001), entity beliefs (β = .12, p = .039), and concentration disruption (β = .12, p = .049). Conclusions Results showed that novelty frustration was positively related to experiencing some negative consequences in PE, which is an important criterion within BPNT. Future training programs aimed at promoting optimal (and preventing detrimental) motivational styles in PE teachers could use these results to optimize students’ PE experiences

Changes in bariatric patients’ physical activity levels and health-related quality of life following a postoperative motivational physical activity intervention

Purpose: Self-determination theory (SDT) has been widely used as a useful motivational framework for improving long-term adherence to physical activity (PA) and health-related quality of life (HRQoL). The aim of this study was to examine the effects of a 6-month motivational PA intervention (MPAI) on bariatric patients’ PA levels and HRQoL from pre-surgery to the end of the MPAI (7 months post-surgery). Additionally, a re-test was performed 13 months post-surgery. Methods: 40 participants undergoing sleeve gastrectomy were assigned to a 6-month MPAI or to a control group. The MPAI was based on techniques and messages from SDT. At baseline and post-intervention measures, both groups wore accelerometers for one week and completed the SF-36 questionnaire. Results: 32 participants (78.1% female) completed all measures and were included in the final analyses. PA levels did not significantly differ between groups as a consequence of the intervention. Clinically significant differences (d ≥ 0.5) favoring the MPAI group were found for SF-36 domains of bodily pain (at pre-surgery, increasing at 7- and 13-months post-surgery), general health and vitality (7 months post-surgery), and physical functioning and the physical component score (both 7- and 13-months post-surgery). Social functioning also showed clinically significant differences favoring the MPAI group at pre-surgery, increasing at 7 months post-surgery. These differences disappeared at 13 months post-surgery. Conclusions: SDT-based PA interventions could enhance several dimensions of bariatric patients’ HRQoL after surgery. Further research is needed to understand what motivational processes are key aspects to promote PA participation in these patients

A self-determined exploration of adolescents’ and parents’ experiences derived from a multidimensional school-based physical activity intervention

Purpose: Adolescents’ and parents’ experiences within a multidimensional schoolbased physical activity intervention grounded on self-determination theory were explored. Method: Qualitative data from 29 adolescents (aged 15-17 years) and three parents on behalf of the total students' families were collected via participant observation (research diary), semistructured interviews, and focus groups. Results: Adolescents perceived that the application of motivational strategies, based on selfdetermination theory, satisfied their basic psychological needs for autonomy, competence and relatedness, favored self-determined motivation, and gave rise to adaptive consequences (improved physical activity knowledge, creation of affective bonds, and increased leisure-time physical activity). These results were supported by the information reported by the students' parents. Discussion/Conclusions: The findings support the implementation of self-determination theory-based multidimensional interventions to promote adolescents’ physical activity participation. This study also presents several motivational strategies which could be useful for the design and implementation of future school-based physical activity intervention

Psychosis and Dandy-Walker syndrome: a case report and review of the literature

Dandy-Walker syndrome (DWS) is a group of brain malformations which sometimes present with psychotic symptoms. We present the case of a patient diagnosed with Dandy-Walker variant who presented with schizophrenia-like psychosis. A man in his 30s was admitted to an acute psychiatric unit presenting with persecutory delusions, auditory hallucinations and violent behaviour. The MRI performed showed the typical alterations of Dandy-Walker variant: vermian hypoplasia and cystic dilatation of the fourth ventricle. He also suffered from mild intellectual disability. After being treated with olanzapine 10 mg/d for a month, his psychotic symptoms greatly improved and he was discharged. In conclusion, DWS may cause psychosis through a dysfunction in the circuit connecting prefrontal, thalamic and cerebellar areas. The association between these two conditions may contribute to the understanding of the aetiopathogenesis of schizophrenia

Peripheral Inflammation Enhances Microglia Response and Nigral Dopaminergic Cell Death in an in vivo MPTP Model of Parkinson’s Disease

The impact of systemic inflammation in nigral dopaminergic cell loss remains unclear. Here, we have investigated the role of peripheral inflammation induced by systemic lipopolysaccharide (LPS) administration in the MPTP-based model of Parkinson’s disease. Brain inflammation, microglia and astroglia activation, disruption of the blood–brain barrier (BBB) and integrity of the nigrostriatal dopaminergic system were evaluated in response to i.p. injection of LPS, MPTP or the combination of both. Our results showed that combinative treatment exacerbates microglia activation and enhances (i) the appearance of galectin-3-positive microglia, recently identified as microglial disease-associated phenotypic marker, (ii) the up-regulation of pro-inflammatory cytokines, (iii) the occurrence of A1 neurotoxic astrocytes, (iv) the breakdown of the BBB, and (v) the loss of dopaminergic neurons in the substantia nigra. Microglia activation was triggered earlier than other degenerative events, suggesting that over-activation of microglia (including different polarization states) may induce dopaminergic neuron loss by itself, initiating the endless cycle of inflammation/degeneration. Our study revitalizes the importance of peripheral inflammation as a potential risk factor for Parkinson’s disease and raises the possibility of using new anti-inflammatory therapies to improve the course of neurodegenerative diseases, including those directly aimed at modulating the deleterious activity of disease-associated microglia.España MINECO y FEDER SAF2015-64171-

Physical education and school bullying: a systematic review

Objectives: To evaluate the associations of physical education (PE) with school violence and bullying. Design: Systematic review. Method: Using a systematic search in Medline, PsycINFO, SPORTDiscus, Web of Science, and Scopus, relevant studies with a quantitative and qualitative design were identified that met previously established eligibility criteria. Quality was assessed (bias risk analysis) and data were extracted from a previously elaborated template. Results: The systematic review finally included 16 studies, of which 10 had a quantitative design (n = 12795), 5 a qualitative design (n = 79) and 1 a mixed design (n = 86). The high heterogeneity presented by the measures used in the included studies hindered the comparison of the outcomes and prevented meta-analysis of the data. Although there is insufficient evidence about the positive impact of PE on bullying prevention, the results of this review indicate that some aspects of PE programs could improve students’ skills to cope with these situations. Conclusions: The results of this review suggest the importance of PE in the prevention of bullying. Secondly, it is emphasized that bullying situations have a negative impact on students’ enjoyment of PE, leading to detrimental consequences for their physical and psychological health. Thirdly, the figure of the PE teacher as a key element to prevent and/or encourage bullying was obvious

Los terceros complejos: la competencia de la Jurisdicción Especial para la Paz

This policy paper presents recommendations to the Colombian Special Jurisdiction for Peace regarding the implementation of its competence over third party actors, in particular economic actors, such as corporate directors, business owners, landowners etc., for their role in conflict related crimes