Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-βInduced Neuronal Death

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer’s disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-β (Aβ) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-β protein precursor (AβPP) synthesis, reduced the AβPP amyloidogenic pathway, resulting in lower Alevels, and blocked the expression of pro-inflammatory cytokines TNFα and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by Aβ accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted

Mental Health in Women Victims of Gender Violence: Descriptive and Multivariate Analysis of Neuropsychological Functions and Depressive Symptomatology

[EN] Female victims of abuse, as well as suffering from psychopathological disorders such as depression, can have neuropsychological sequelae affecting memory and attention, with serious consequences, both physical and psychological, in their daily lives. Therefore, the objective of this study is to analyse these sequelae that affect attention and memory, as well as the possible association of these sequelae to depression. A total of 68 women, victims of gender-based violence, between the ages of 15 and 62 participated in this study. The Luria DNA Battery (Neuropsychological Diagnosis of Adults) by Manga and Ramos (2000); and the Beck Depression Inventory (2011) were applied. It is shown that female victims of gender-based violence present poor short-term memory, attentional control, and score low on the Luria-DNA battery. Of these women, 60% suffer from some relevant type of depression. Through HJ-Biplot analysis, a direct relationship was found between memory and attentional control with the total score of the Luria battery. However, an inverse relationship was found between short-term memory and depression. In addition, three well-differentiated clusters of female victims of gender-based violence were identified. It is concluded that a lower rate of depression is observed in female victims of abuse when they have a more intact short-term memory

Social services for the elderly: a multivariate perspective study

[EN] Introduction: Today’s society is aware that healthy aging favors quality of life in the future, even more so as life expectancy increases in populations such as Europe. As in countries such as Japan, it is necessary for institutions to provide social services to support the elderly, with the aim of achieving an optimal quality of life for these people. The aim of this study is to analyze the different types of social services and activities that certain institutions provide to the elderly in order to find areas for improvement or to propose relationships between them that will benefit both users and institutions. Methods: Official data from Junta de Castilla y León (Spain) on social services for the elderly in the 9 provinces of the autonomous community of Castilla y León from 2007 to 2021 were analysed using multivariate statistical techniques. Results: Throughout the period under analysis, there is an association between the number of places in public and private non-profit residential centers for the elderly and the number of places in day-care centers or the number of students in the Inter-University Experience Programme. The variables associated with the telecare programme are related to the number of people under guardianship. On the other hand, three well-differentiated clusters of provinces of Castilla y León were observed. Discussion: Our findings have implications for the quality of life of the elderly, as the differences in social services in the areas analysed have a direct impact on the health of the elderly

Stakeholders y responsabilidad social universitaria en la Universidad Nacional de San Antonio Abad del Cusco

The objective of the research was to identify the perception of internal and external stakeholders regarding the university social responsibility fulfilled by the National University of San Antonio Abad in Cusco (UNSAAC). For this purpose, a qualitative, descriptive, and nonexperimental basic research was carried out, with a probabilistic sample of 211 internal stakeholders and a non-probabilistic sample of 49 external stakeholder representatives. Surveys and interview techniques were applied. The results showed that the most of the internal stakeholders perceive that the university social responsibility is moderately acceptable in the four axes of social responsibility (management, training, cognition and social perception), on the other hand, an important part of the external stakeholders perceive that the university is disconnected from the organizations of its local and regional environment, especially in the aspects of management and research, nevertheless consider that the university is an organization potentially allied to its institutional activities.El objetivo de la investigación fue identificar la percepción de los Stakeholders internos y externos respecto a la responsabilidad social universitaria que cumple la Universidad Nacional de San Antonio Abad del Cusco (UNSAAC).  Con tal propósito, se efectuó una investigación básica, cualitativa, descriptiva y no experimental, con una muestra probabilística de 211 de Stakeholders internos y una muestra no probabilística de 49 representantes de stakeholder externos. Se aplicaron las técnicas de encuesta y entrevista. Los resultados evidenciaron que la mayor parte de los Stakeholders internos perciben que la responsabilidad social universitaria de la entidad es medianamente aceptable en los cuatro ejes de la responsabilidad social (gestión, formación, cognición y participación social), en cambio, una parte importante de los Stakeholders externos perciben que la universidad se encuentra desvinculada de las organizaciones de su entorno local y regional, especialmente en los aspectos de gestión e investigación, no obstante consideran que la universidad es una organización potencialmente aliada a sus actividades institucionales

Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited. However, the development of these dendritic nanocarriers is challenging because of the undesired and/or premature degradation observed during their synthesis and/or application. Here, we report new hybrid-biodegradable, biocompatible, non-toxic, and water-soluble azide-terminated PEG–GATGE dendritic block copolymers, based on a gallic acid (GA) core and triethylene glycol (TG) butanoate arms, incorporating ester bonds (E) at the dendritic arms/shell. Their successful functionalization by “click” chemistry with unprotected alkynated amines allowed complexation and delivery of siRNA. The hydrophobic character of the GATGE building unit confers to these hydrolyzable dendritic bionanomaterials a great ability to complex, protect and mediate the cellular internalization of siRNA. Moreover, the localization of the degradation points at the dendritic periphery, close to the complexed siRNA, was found to be important for nucleic acid release from the nanoparticles, rendering a significant improvement of the transfection efficiency compared to their hydrolytically stable PEG–GATG copolymer counterparts. The present study puts forward these biodegradable PEG–dendritic block copolymers not only as suitable vectors for nucleic acids, but also as new avenues for further developments exploring their use in theranosticsThe authors would like to acknowledge the FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE and the Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia (PTDC/CTM-NAN/112428/2009 and PTDC/CTM-NAN/3547/2014) that supported this work and the FCT / MEC through National Funds and, when applicable, co-financed by the FEDER via the PT2020 Partnership Agreement under the 4293 Unit I&D. V. Leiro acknowledges the support by FCT (SFRH/BPD/69110/2010) and by the project NORTE-01-0145-FEDER-000012, financed by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). P.M.D. Moreno acknowledges the support from the Marie Curie Actions of the European Community’s Seventh Framework Program (PIEF-GA-2011-300485) and FCT fellowship (SFRH/BPD/108738/2015). This work was also financially supported by the Spanish Government (MINECO: CTQ2012-34790, CTQ2012-33436) and the Xunta de Galicia (CN2011/037)S

Promoción de exportación para las PyMEs

El presente trabajo tiene por finalidad revelar la incidencia que tienen las pequeñas y medianas empresas argentinas en el mercado internacional y los instrumentos con los que cuentan para acceder a dicho mercado. Para ello, se analizó el comercio exterior en su conjunto, principalmente, sus actores, operatoria, incoterms, entre otros. Se aplicaron métodos cuantitativos a través de la presentación de gráficos con datos estadísticos para conocer los porcentajes de exportación de las PyMEs en la Argentina. Los resultados obtenidos por un lado, indican la gran importancia que tienen estas empresas en las operaciones de extracción de mercadería que se realizan en nuestro país y por el otro, la falta de formación para insertarse al comercio exterior de una manera más competitiva. El objetivo de este informe es dar a conocer herramientas existentes que provocan beneficios y facilitan la introducción al mercado externo para las pequeñas y medianas empresas.Fil: Gazze, Omar Carim. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Naranjo Vega, Ana Victoria Lourdes. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Ticli, Brunela Elena. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas

Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-beta-Induced Neuronal Death

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer's disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD-associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-beta (A beta) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A beta-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A beta-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-beta protein precursor (A beta PP) synthesis, reduced the A beta PP amyloidogenic pathway, resulting in lower A beta levels, and blocked the expression of pro-inflammatory cytokines TNF alpha and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by A beta accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted.Peer ReviewedPostprint (author's final draft

Niñas migrantes y mutilación genital femenina: los números cuentan que ...

[ES] La mutilación genital femenina, atenta claramente contra la salud física y psicológica, así como hacia los derechos humanos de aquellas niñas que la sufren. El aumento de los movimientos migratorios hacia países occidentales visibiliza este tema. Objetivo: Determinar la incidencia de la mutilación genital femenina en las mujeres migrantes. Metodología: Se realizó un estudio sobre niñas en riesgo de mutilación genital femenina que migraron a la Unión Europea desde países africanos. Resultados: En la última década el número de niñas migrantes con estas características se va reduciendo. La mayoría de las migraciones son del oeste de África. Italia y Francia son los países europeos que más niñas reciben. Con escenarios de alto y bajo riesgo de mutilación se observaron diferencias según región de origen y país europeo de destino. [EN] Female genital mutilation clearly undermines the physical and psychological health, as well as the human rights of those girls who suffer it. The increase in migratory movements towards western countries makes this issue visible. Objective: To determine the incidence of female genital mutilation in migrant women. Methodology: A study was carried out on girls at risk of female genital mutilation who migrated to the European Union from African countries. Results: In the last decade the number of migrant girls with these characteristics has been decreasing. Most of the migrations are from West Africa. Italy and France are the European countries that receive the most girls. With scenarios of high and low risk of mutilation, differences were observed according to the region of origin and the European country of destination

Social services for the elderly: a multivariate perspective study

IntroductionToday’s society is aware that healthy aging favors quality of life in the future, even more so as life expectancy increases in populations such as Europe. As in countries such as Japan, it is necessary for institutions to provide social services to support the elderly, with the aim of achieving an optimal quality of life for these people. The aim of this study is to analyze the different types of social services and activities that certain institutions provide to the elderly in order to find areas for improvement or to propose relationships between them that will benefit both users and institutions.MethodsOfficial data from Junta de Castilla y León (Spain) on social services for the elderly in the 9 provinces of the autonomous community of Castilla y León from 2007 to 2021 were analysed using multivariate statistical techniques.ResultsThroughout the period under analysis, there is an association between the number of places in public and private non-profit residential centers for the elderly and the number of places in day-care centers or the number of students in the Inter-University Experience Programme. The variables associated with the telecare programme are related to the number of people under guardianship. On the other hand, three well-differentiated clusters of provinces of Castilla y León were observed.DiscussionOur findings have implications for the quality of life of the elderly, as the differences in social services in the areas analysed have a direct impact on the health of the elderly

Impacto psicológico de la emigración en América y Europa

[ES] Al emigrar las personas se ven expuestas a experiencias difíciles que repercuten en la salud psicológica pudiendo manifestar: ansiedad, depresión, baja autoestima, e incluso desarrollar el síndrome de Ulises. Objetivo: Identificar el impacto psicológico de los emigrantes en América y Europa. Metodología: Se llevó a cabo un estudio sobre datos migratorios de diversos países, proporcionados por el Departamento de Asuntos Económicos y Sociales de las Naciones Unidas. Resultados: La población de países latinoamericanos no siempre migra a los lugares más cercanos. Los mexicanos emigraron más a Norteamérica mientras que los venezolanos suelen viajar a países latinoamericanos. Conclusiones: Los emigrantes tienden a buscar mejores condiciones de vida, sin considerar el riesgo de perder sus derechos como personas