Late-life depression accelerates cognitive impairment and tau-associated pathology in an Alzheimer´s disease model.

Clinical studies suggest that depression could be considered an important risk factor for the future development of cognitive impairment and Alzheimer's disease (AD). In fact, there is a strong association between late-life depression and AD. The age of AD onset has been shown to be accelerated in patients with mild cognitive impairment (MCI) with a history of depression, and women appear to be particularly more vulnerable to this condition. In addition, individuals with MCI who present depressive symptoms have an elevated burden of amyloid-beta (Aβ), the main toxic protein associated with Alzheimer's pathology, and a higher risk of developing AD compared to non-depressed MCI patients. Although it has been described that some transgenic models of AD can develop signs similar to depression in advanced stages, the induction of Alzheimer's pathology due to a depressive process has not been studied under experimental conditions to emulate late-life depression as a risk factor for AD. In this study, we induced chronic unpredictable mild stress (CUMS) in P301S tau transgenic mice to determine whether depression is a cause, rather than a consequence, of the development of AD pathology. Our results suggest that transgenic tau mice subjected to CUMS seem to develop a depressive state. This animals display enhanced cognitive impairment compared to controls. In addition, histological studies show increased tau deposition, suggesting that late-life depression could worse AD progression by accelerating tau aggregation and worsening clinical signs. The findings generated in this project could provide evidence of depression as a risk factor for AD, providing new insights on molecular mechanisms involved in AD onset and progression.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Late-life depression accelerates cognitive decline in a tauopathy mouse model

Background: Clinical studies suggest that depressive symptoms could be considered an important risk factor for the future development of cognitive impairment and even Alzheimer's disease (AD). In fact, there is a strong association between depression in later life and AD. The age of onset of AD has been shown to be accelerated in patients with mild cognitive impairment (MCI) with a history of depression, and women appear to be particularly more vulnerable to this condition. In addition, individuals with MCI who present depressive symptoms have an elevated burden of amyloid-beta, one of the featured toxic proteins associated with Alzheimer's pathology, and a higher risk of developing AD compared to non-depressed MCI patients. Although it has been described that some transgenic models of AD can develop signs similar to depression in advanced stages, it is unknown whether late-life depression can accelerate tau-associated pathology and, therefore, acting as a risk factor for AD. Method: In this study, we induced chronic unpredictable mild stress (CUMS) in P301S tau transgenic mice to determine whether depression is a cause, rather than a consequence, of the development of AD. Result: The results of our study indicate that the induction of CUMS in transgenic animals induces phenotypic changes related to a depressive state. Conclusion: The findings obtained after inducing late-life depression-like in P301S mice indicate that depression could be considered a risk factor for AD, by accelerating tau aggregation and worsening clinical signs.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

La representación de la ecología en la prensa online-only española : análisis cuantitativo e implicaciones ideológicas

Esta investigación pretende aportar evidencia empírica para delinear el perfil ideológico de la prensa digital online-only española en un aspecto socio- cultural concreto: la representación y valoración de temas medioambientales. En línea con investigaciones previas que han abordado el estudio ideológico-político de este tipo de prensa, y a partir de un marco teórico sobre prensa online e ideología, nuestra hipótesis afirma que la opinión digital española se ha movido en los últimos años en una dirección progresista en cuestiones ecológicas. Para comprobarlo, utilizamos una muestra empírica de los diarios digitales más consultados, escogiendo como unidades de muestreo un conjunto de columnas de opinión (género donde el sesgo ideológico suele ser más o menos evidente) de dos momentos distintos en el tiempo, en un intervalo de 5 años. La muestra es sometida a un análisis de contenido centrado fundamentalmente en 3 categorías de análisis: ecología / medioambiente, lucha contra el cambio climático, y energía nuclear. Junto a las menciones de cada categoría se tiene en cuenta la valoración que hace el columnista sobre dichas menciones. Además de estas categorías de análisis, el estudio incluye la cuantificación del tipo de objeto y el tema principal de cada columna. Los datos señalan una evolución en el tiempo que indica una mayor conciencia medioambiental en el periodismo de opinión online-only español, de forma que, a la altura de 2016, la consideración de las cuestiones ecológicas es más favorable

Cognitive impairment acceleration after late-life depression in a model of Alzheimer´s disease

Background: Clinical studies suggest that depressive symptoms could be considered an important risk factor for the future development of cognitive impairment and even Alzheimer's disease (AD). In fact, there is a strong association between depression in later life and AD. The age of onset of AD has been shown to be accelerated in patients with mild cognitive impairment (MCI) with a history of depression, and women appear to be particularly more vulnerable to this condition. In addition, individuals with MCI who present with depressive symptoms have an elevated burden of amyloid-beta (Aβ), the main toxic protein associated with Alzheimer's pathology, and a higher risk of developing AD compared to non-depressed MCI patients. However, it is unknown whether depression can be considered a risk factor for the development of AD. Although it has been described that some transgenic models of AD can develop signs similar to depression in advanced stages, the induction of Alzheimer's pathology due to a depressive process has not been studied under experimental conditions to emulate late-life depression as a risk factor for AD. Method: In this study, we induced chronic unpredictable mild stress (CUMS) in P301S tau transgenic mice to determine whether depression is a cause, rather than a consequence, of the development of AD. Result: The results of our study indicate that the induction of CUMS in transgenic animals of the disease give rise to changes in depressive state of the animals. Conclusion: The findings generated in this project could provide evidence of depression as a risk factor for AD, its mechanisms of action, use as early biomarkers, as well as the discovery of new therapies for AD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Ministerio de Ciencia e Innovación Brain and Behavior Research Foundation Fondos FEDER y Universidad de Málag

Neurons and astrocytes derived from human iPSCs to model Alzheimer´s disease

Alzheimer's disease (AD) is characterized by presenting a complex pathology, not fully resolved yet. This fact, together with the lack of reliable models, has impeded the development of effective therapies. Recently, several studies have shown that functional glial cell defects have a key role in the pathology of AD. However, this glial dysfunction, currently, cannot be correctly modeled using the available animal models, so we hypothesized that cells derived from Alzheimer's patients can serve as a better platform for studying the disease. In this sense, human pluripotent stem cells (hPSC) allow the generation of different types of neural cells, which can be used for disease modeling, identification of new targets and drugs development. Methods: We have a collection of hiPSCs derived from patients with sporadic forms of AD stratified based on APOE genotype. We have differentiated these cells towards neural cells and mature them to neurons or astrocytes using a serum-free approach, to assess intrinsic differences between those derived from AD patients or healthy controls. Results: We have implemented a serum-free approach and generated neural precursors and astrocytes from all the lines tested. We observe differences at the phenotypic level and a reduced capacity to differentiate towards neural lineage in those lines derived from APOE4 carriers. Conclusions: Our preliminary data suggest intrinsic differences in the neural differentiation capacity between cell lines derived from APOE4 or APOE3 carrier subjects. Further experiments would contribute to elucidate novel pathogenic pathways associated with neurodegeneration and susceptible of therapeutic modulation, likely contributing to the development of new effective drugs against AD.This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI21/00915 (to AG) and PI21/00914 (to JV); by Junta de Andalucia through Consejería de Economía y Conocimiento grants PY18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014-2020, Consejeria de Salud grant PI-0276-2018 (to JAGL) and Programa Operativo de Empleo Juvenil SNGJ4-11 to LCP. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Glia and neurons from human iPSCs to address the pathology of Alzheimer´s disease

Alzheimer's disease (AD) is characterized by presenting a complex pathology, not fully resolved yet. This fact, together with the lack of reliable models, has impeded the development of effective therapies. Recently, several studies have shown that functional glial cell defects have a key role in the pathology of AD. However, this glial dysfunction, currently, cannot be correctly modeled using the available animal models, so we hypothesized that cells derived from Alzheimer's patients can serve as a better platform for studying the disease. In this sense, human pluripotent stem cells (hPSC) allow the generation of different types of neural cells, which can be used for disease modeling, identification of new targets and drugs development. Methods: We have a collection of hiPSCs derived from patients with sporadic forms of AD stratified based on APOE genotype. We have differentiated these cells towards neural cells and mature them to neurons or astrocytes using a serum-free approach, to assess intrinsic differences between those derived from AD patients or healthy controls. Results: We have implemented a serum-free approach and generated neural precursors and astrocytes from all the lines tested. We observe differences at the phenotypic level and a reduced capacity to differentiate towards neural lineage in those lines derived from APOE4 carriers. Conclusions: Our preliminary data suggest intrinsic differences in the neural differentiation capacity between cell lines derived from APOE4 or APOE3 carrier subjects. Further experiments would contribute to elucidate novel pathogenic pathways associated with neurodegeneration and susceptible of therapeutic modulation, likely contributing to the development of new effective drugs against AD.This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI21/00915 (to AG) and PI21/00914 (to JV); by Junta de Andalucia through Consejería de Economía y Conocimiento grants UMA20-FEDERJA-048 (to JAGL), PY18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014-2020, and Programa Operativo de Empleo Juvenil SNGJ4-11 to LCP. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Impulsando la competitividad internacional de la empresa turística en España: Una agenda de cambio institucional

In a context in which tourism destinations are increasingly seeing the internationalisation of their enterprises, as well as the setting up of foreign businesses there, it becomes a point of interest to know the circumstances under which tourism enterprises can maintain and strengthen their international competitiveness. In order to make a contribution in this area, the present work identifies –in the case of Spain– the necessary changes to the cognitive, normative and regulatory institutional pillars so as to favour the international competitiveness of tourism businesses established in the country. To this end, empirical research has been carried out in two phases, the first qualitative and the second quantitative. The work done makes it possible to identify and prioritise in terms of importance 37 changes to the institutional pillars and 139 more specific measures, which would contribute to improving the international competitiveness of the enterprises in the tourism sector. Given that the competitiveness of enterprises in a country affects their results and their survival, as well as the socio-economic prosperity of the territory, the work presented is of practical utility both for entrepreneurs and business associations, and for those responsible for formulating laws and policies that support the tourism sector in Spain, since all are necessary and responsible actors in the development of the required institutional changes.Este trabajo ha obtenido el 1.er Premio «Estudios Financieros» 2019 en la modalidad de Contabilidad y Administración de Empresas. En un contexto en el que los destinos turísticos asisten de forma creciente tanto a la internacionalización de sus empresas como a la instalación en ellos de empresas foráneas, adquiere elevado interés conocer las circunstancias bajo las cuales la empresa turística puede mantener y reforzar su competitividad internacional. En aras de realizar una contribución en este ámbito, el presente trabajo identifica, para el caso de España, los cambios necesarios en los pilares institucionales cognitivo, normativo y regulativo al objeto de favorecer la competitividad internacional de la empresa turística establecida en el país. A tal objeto se lleva a cabo un trabajo empírico en dos fases, la primera de índole cualitativa y la segunda cuantitativa. El trabajo realizado permite identificar y priorizar 37 cambios en los pilares institucionales, y su concreción en 139 propuestas, que contribuirían a mejorar la competitividad internacional de las empresas del sector. Dado que la competitividad de las empresas de un país afecta a los resultados y supervivencia de estas, así como a la prosperidad socioeconómica del territorio, el trabajo que se presenta es de utilidad práctica tanto para empresarios y asociaciones empresariales como para los responsables de formular leyes y políticas de apoyo al sector turístico en España, pues todos son actores necesarios y con responsabilidad en el desarrollo del cambio institucional requerido

Co-cultures between neurons and astrocytes to address Alzheimer´s disease pathology.

Background: Alzheimer's disease (AD) is characterized by presenting a complex pathology, not fully resolved yet. This fact, together with the lack of reliable models, has impeded the development of effective therapies. Recently, several studies have shown that functional glial cell defects have a key role in the pathology of AD. However, this glial dysfunction, currently, cannot be correctly modeled using the available animal models, so we hypothesized that cells derived from Alzheimer's patients can serve as a better platform for studying the disease. In this sense, human pluripotent stem cells (hPSC) allow the generation of different types of neural cells, which can be used for disease modeling, identification of new targets and drugs development. Methods: We have a collection of hiPSCs derived from patients with sporadic forms of AD stratified based on APOE genotype. We have differentiated these cells towards neural cells and mature them to neurons or astrocytes using a serum-free approach, to assess intrinsic differences between those derived from AD patients or healthy controls. Results: We have implemented a serum-free approach and generated neural precursors and astrocytes from all the lines tested. We observe differences at the phenotypic level and a reduced capacity to differentiate towards neural lineage in those lines derived from APOE4 carriers. Conclusions: Our preliminary data suggest intrinsic differences in the neural differentiation capacity between cell lines derived from APOE4 or APOE3 carrier subjects. Further experiments would contribute to elucidate novel pathogenic pathways associated with neurodegeneration and susceptible of therapeutic modulation, likely contributing to the development of new effective drugs against AD.This study was supported by ISCiii (Spain), co-financed by FEDER funds, through grants PI21/00915 (AG) and PI21/00914 (JV); by Junta de Andalucia through Consejería de Economía and Conocimiento grants UMA20-FEDERJA-048 (JAGL), PY18-RT-2233 (to AG) and US-1262734 (JV), co-financed by Programa Operativo FEDER 2014-2020, and SNGJ4-11 (LCP). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Nodopathies in the Early Diagnosis of Axonal Forms of Guillain-Barré Syndrome

[EN] Introduction: Guillain-Barré syndrome (GBS) has been classified into demyelinating and axonal subtypes or forms, such as acute motor axonal neuropathy (AMAN) and regional pharyngeal-cervical-brachial variant (PCBv). Objective: To study the relationship between motor nerve conduction blocks (CBs) and prognosis in AMAN and PCBv. Patients and Methods: We retrospectively analyzed six cases of AMAN and PCBv with serial nerve conduction studies (NCS) and electromyography (EMG). Results: The serial NCS (1st−2nd and 3rd week) showed, as the most constant data, a decreased amplitude of the compound muscle action potential (CMAP) in 100% of cases. CBs were present in 66.6% of cases. EMG (3rd week) showed signs of severe denervation in 33.3%. All patients were treated from the 1st−2nd week of evolution with intravenous immunoglobulins (IVIGs). Patients with CBs (1st−2nd and 3rd week), showed reversible CBs or reversible conduction failure (RCF) and complete recovery at 1 month. Patients without CBs, with persistent reduced distal CMAP amplitude (dCMAP), showed severe acute denervation due to axonal degeneration (3rd week and 1st−3rd month) and a slow recovery of several months. Conclusions: Not all axonal forms of GBS have a poor prognosis. This study of AMAN and PCBv shows that patients with CBs can have reversible CBs or RCF, and good prognosis. Patients without CBs, with persistent reduction of dCMAP amplitude decrement, have severe acute denervation, and a worse prognosis. AMAN and PCBv have a continuous spectrum ranging from CBs due to dysfunction/disruption of Nodes of Ranvier, called nodopathies, with reversible CBs or RCF and good prognosis, to axonal degeneration with worse prognosisS

Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review

The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin’s lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy