Germinal Matrix-Intraventricular Hemorrhage of the Preterm Newborn and Preclinical Models: Inflammatory Considerations

The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most important complications of the preterm newborn. Since these children are born at a critical time in brain development, they can develop short and long term neurological, sensory, cognitive and motor disabilities depending on the severity of the GM-IVH. In addition, hemorrhage triggers a microglia-mediated inflammatory response that damages the tissue adjacent to the injury. Nevertheless, a neuroprotective and neuroreparative role of the microglia has also been described, suggesting that neonatal microglia may have unique functions. While the implication of the inflammatory process in GM-IVH is well established, the difficulty to access a very delicate population has lead to the development of animal models that resemble the pathological features of GM-IVH. Genetically modified models and lesions induced by local administration of glycerol, collagenase or blood have been used to study associated inflammatory mechanisms as well as therapeutic targets. In the present study we review the GM-IVH complications, with special interest in inflammatory response and the role of microglia, both in patients and animal models, and we analyze specific proteins and cytokines that are currently under study as feasible predictors of GM-IVH evolution and prognosis

Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer's Disease and Type 2 Diabetes

Alzheimer's disease is the most common form of dementia, and epidemiological studies support that type 2 diabetes (T2D) is a major contributor. The relationship between both diseases and the fact that Alzheimer's disease (AD) does not have a successful treatment support the study on antidiabetic drugs limiting or slowing down brain complications in AD. Among these, liraglutide (LRGT), a glucagon-like peptide-1 agonist, is currently being tested in patients with AD in the Evaluating Liraglutide in Alzheimer's Disease (ELAD) clinical trial. However, the effects of LRGT on brain pathology when AD and T2D coexist have not been assessed. We have administered LRGT (500 mu g/kg/day) to a mixed murine model of AD and T2D (APP/PS1xdb/db mice) for 20 weeks. We have evaluated metabolic parameters as well as the effects of LRGT on learning and memory. Postmortem analysis included assessment of brain amyloid-beta and tau pathologies, microglia activation, spontaneous bleeding and neuronal loss, as well as insulin and insulin-like growth factor 1 receptors. LRGT treatment reduced glucose levels in diabetic mice (db/db and APP/PS1xdb/db) after 4 weeks of treatment. LRGT also helped to maintain insulin levels after 8 weeks of treatment. While we did not detect any effects on cortical insulin or insulin-like growth factor 1 receptor m-RNA levels, LRGT significantly reduced brain atrophy in the db/db and APP/PS1xdb/db mice. LRGT treatment also rescued neuron density in the APP/PS1xdb/db mice in the proximity (p = 0.008) far from amyloid plaques (p < 0.001). LRGT reduced amyloid plaque burden in the APP/PS1 animals (p < 0.001), as well as A beta aggregates levels (p = 0.046), and tau hyperphosphorylation (p = 0.009) in the APP/PS1xdb/db mice. Spontaneous bleeding was also ameliorated in the APP/PS1xdb/db animals (p = 0.012), and microglia burden was reduced in the proximity of amyloid plaques in the APP/PS1 and APP/PS1xdb/db mice (p < 0.001), while microglia was reduced in areas far from amyloid plaques in the db/db and APP/PS1xdb/db mice (p < 0.001). This overall improvement helped to rescue cognitive impairment in AD-T2D mice in the new object discrimination test (p < 0.001) and Morris water maze (p < 0.001). Altogether, our data support the role of LRGT in reduction of associated brain complications when T2D and AD occur simultaneously, as regularly observed in the clinical arena.CH-B: predoctoral fellowship. University of Cadiz. PA-M: predoctoral fellowship. Instituto de Investigacion Biomedica de la Provincia de Cadiz (INIBICA). MG-A: Agencia Estatal de Investigacion. Ministerio de Ciencia e Innovacion. Programa Estatal de Generacion de Conocimiento y Fortalecimiento Cientifico y Tecnologico del Sistema de I C D C i y del Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2017-2020 (PID2020115499RB-I0). Programa Estatal de I C D C I orientada a los Retos de la Sociedad (BFU 2016-75038-R), financed by the Agencia Estatal de Investigacion (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER), Ministerio de Ciencia, Innovacion y Universidades. Subvencion para la financiacion de la Investigacion y la Innovacion Biomedica y en Ciencias de la Salud en el Marco de la Iniciativa Territorial Integrada 2014-2020 para la Provincia de Cadiz. Consejeria de Salud. Junta de Andalucia. Union Europea, financed by the Fondo de Desarrollo Regional (FEDER) (PI-0008-2017)

Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha

Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6-month-old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor-alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging.19 página

Estrategias Docentes Colaborativas para el Desarrollo de la Competencia Transversal de Innovación, Creatividad y Emprendimiento [Collaborative Teaching Strategies to Develop Skills in Innovation, Creativity and Entrepreneurship]

Una de las competencias transversales que entraña mayor grado de dificultad en su implementación, adquisición a todos los niveles, y evaluación es la de “Innovación, creatividad y emprendimiento”. La innovación se entiende como la capacidad de dar respuesta satisfactoria a las necesidades personales, organizativas y sociales, modificando procesos y/o resultados para generar nuevo valor. La innovación necesita ir acompañada de la creatividad para generar ideas y del emprendimiento para transformar las ideas en un producto de valor. En este trabajo se describe el diseño de estrategias docentes integradas en el marco de la corriente de educación emprendedora, centradas en el aprendizaje basado en problemas y colaborativo, para desarrollar dicha competencia. La acción se lleva a cabo en diferentes asignaturas de primer curso en distintos títulos de Grado en la Universitat Politècnica de València. Se describen las acciones realizadas, se analizan los resultados obtenidos y se valora la transferibilidad a otros contextos, tras la implementación del plan de trabajo para cada asignatura. Se concluye que las acciones llevadas a cabo han contribuido a desarrollar la competencia indicada y a que los estudiantes experimenten el valor del aprendizaje activo y del trabajo colaborativo. [One of the most difficult transversal competences to implement, acquire at all levels and evaluate, is that of "Innovation, creativity and entrepreneurship". Innovation is understood as the ability to satisfy personal, organizational and social needs, modifying processes and/or results to generate new value. Innovation needs to be accompanied by creativity to generate ideas and by entrepreneurship to transform ideas into a valuable product. This paper describes the design of teaching strategies integrated within the framework of entrepreneurship education, focused on problem-based and collaborative learning, to develop this competence. The experiences are carried out in different first year subjects from different degrees offered by the Universitat Politècncia de València. After the implementation of the work plan for each subject, actions performed are described and results obtained are analysed in order to assess the transferability to other contexts. It is concluded that the actions carried out contributed to develop the indicated skill and allowed students to experience the value of active learning and collaborative work.

Estrategias Participativas para el Desarrollo y Evaluación de Competencias Transversales

[EN] The need to advance the planning, development and evaluation of skills has led to the Grupo de Innovación e Investigación en Metodologías Activas (GIIMA), to consider a project with the aim of developing a methodology that is valid and applicable to a set of cross-disciplinary skills in first degree courses. Participatory methodologies are an effective alternative to facilitate the development of attitudes, skills and abilities, hence the desirability of providing students opportunities and strategies that motivate them in the execution of their tasks, allow them to learn from experience and mistakes, and conclude that in learning how to. These actions, accompanied by a monitoring and evaluation process, may certify skills acquired with the implementation of participatory strategies conveniently chosen by teachers to achieve the results of apprentice. So, it is necessary to design and put in place processes of evaluation and accreditation of skills, and that this type of learning outcomes acquired by the students, also have their social recognition and are valued by employers. The project involves 11 subjects that are taught in 13 undergraduate degrees of the UPV[ES] La necesidad de avanzar en la planificación, desarrollo y evaluación de competencias transversales ha motivado al GRUPO DE INNOVACIÓN E INVESTIGACIÓN EN METODOLOGÍAS ACTIVAS (GIIMA) a plantear un proyecto con el objetivo de desarrollar una metodología que resulte válida y aplicable a un conjunto de competencias transversales en los primeros cursos del Grado. Las metodologías participativas son una alternativa eficaz para facilitar el desarrollo de actitudes, habilidades y destrezas, de ahí la conveniencia de proporcionar a los estudiantes universitarios oportunidades y estrategias que les motiven en la ejecución de sus tareas, les permitan aprender de la experiencia y de los errores, y que concluyan en aprender a hacer. Estas acciones, acompañadas de un seguimiento y evaluación del proceso, podrán acreditar las competencias transversales adquiridas con la implementación de estrategias participativas convenientemente elegidas por los profesores para alcanzar los resultados de aprendizaje deseados. Para ello es necesario diseñar y poner en marcha procesos de evaluación y acreditación de las competencias transversales, y que este tipo de resultados de aprendizaje, adquiridos también por los estudiantes, tengan su reconocimiento social y sean valorados por los empleadores. En el proyecto participan 11 asignaturas que se imparten en 13 titulaciones de Grado de la UPV.Monreal Mengual, L.; Atienza Boronat, MJ.; Badía Valiente, JD.; Bautista, I.; Climent Olmedo, MJ.; Gómez Ángel, B.; Iborra Chornet, S.... (2015). Estrategias Participativas para el Desarrollo y Evaluación de Competencias Transversales. En In-Red 2015 - CONGRESO NACIONAL DE INNOVACIÓN EDUCATIVA Y DE DOCENCIA EN RED. Editorial Universitat Politècnica de València. https://doi.org/10.4995/INRED2015.2015.1626OC

Fostering English-taught higher education programs in a Spanish university: the "TechEnglish" innovative project

In recent years, coinciding with adjustments to the Bologna process, many European universities have attempted to improve their international profile by increasing course offerings in English. According to the Institute of International Education (IIE), Spain has notably increased its English-taught higher education programs, ranking fifth in the list of European countries by number of English-taught Master's programs in 2013. This article presents the goals and preliminary results of an on-going innovative education project (TechEnglish) that aims to promote course offerings in English at the Technical University of Madrid (Universidad Politécnica de Madrid, UPM). The UPM is the oldest and largest of all Technical Universities in Spain. It offers graduate and postgraduate programs that cover all the engineering disciplines as well as architecture. Currently, the UPM has no specific bilingual/multilingual program to promote teaching in English, although there is an Educational Model Whitepaper (with a focus on undergraduate degrees) that promotes the development of activities like an International Semester or a unique shared curriculum. The TechEnglish project is an attempt to foster courses taught in English at 7 UPM Technical Schools, including students and 80 faculty members. Four tasks were identified: (1) to design a university wide framework to increase course offerings, (2) to identify administrative difficulties, (3) to increase visibility of courses offered, and (4) to disseminate the results of the project. First, to design a program we analyzed existing programs at other Spanish universities, and other projects and efforts already under way at the UPM. A total of 13 plans were analyzed and classified according to their relation with students (learning), professors (teaching), administration, course offerings, other actors/institutions within the university (e.g., language departments), funds and projects, dissemination activities, mobility plans and quality control. Second, to begin to identify administrative and organizational difficulties in the implementation of teaching in English, we first estimated the current and potential course offerings at the undergraduate level at the UPM using a survey (student, teacher and administrative demand, level of English and willingness to work in English). Third, to make the course offerings more attractive for both Spanish and international students we examined the way the most prestigious universities in Spain and in Europe try to improve the visibility of their academic offerings in English. Finally, to disseminate the results of the project we created a web page and a workspace on the Moodle education platform and prepared conferences and workshops within the UPM. Preliminary results show that increasing course offerings in English is an important step to promote the internationalization of the University. The main difficulties identified at the UPM were related to how to acknowledge/certify the departments, teachers or students involved in English courses, how students should register for the courses, how departments should split and schedule the courses (Spanish and English), and the lack of qualified personnel. A concerted effort could be made to increase the visibility of English-taught programs offered on-line

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro

Polyphosphate (polyP), a phosphate polymer released by activated platelets, may modulate various stages of hemostasis by binding to blood proteins. In this context, we previously reported that polyP binds to the von Willebrand factor (VWF). One of the most significant functions of VWF is to bind to and protect the blood circulating Factor VIII (FVIII). Therefore, here, we study the role of polyP in the VWF&ndash;FVIII complex in vitro and suggest its biological significance. Surface plasmon resonance and electrophoretic mobility assays indicated that polyP binds dynamically to VWF only in the absence of FVIII. Using the VWF Ristocetin Cofactor assay, the most accepted method for studying VWF in platelet adhesion, we found that polyP activates this role of VWF only at low levels of FVIII, such as in plasmas with chemically depleted FVIII and plasmas from severe hemophilia A patients. Moreover, we demonstrated that FVIII competes with polyP in the activation of VWF. Finally, polyP also increases the binding of VWF to platelets in samples from patients with type 2 and type 3 von Willebrand disease. We propose that polyP may be used in designing new therapies to activate VWF when FVIII cannot be used