Amyloid-driven tau accumulation on mitochondria potentially leads to cognitive deterioration in alzheimer’s disease

Despite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer’s disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the present study, an adeno-associated virus (AAV9) carrying the mutant P301L form of human tau, was injected into the dorsal hippocampi of APP/PS1 transgenic mice or wild type mice (WT). Three months after injections, memory tasks, biochemical and immunohistochemical analysis were performed. We found that the overexpression of hTauP301L accelerates memory deficits in APP/PS1 mice, but it did not affect memory function of WT mice. Likewise, biochemical assays showed that only in the case of APP/PS1-hTauP301L injected mice, an important accumulation of tau was observed in the insoluble urea fraction. Similarly, electron microscopy images revealed that numerous clusters of tau immunoparticles appear at the dendrites of APP/PS1 injected mice and not in WT animals, suggesting that the presence of amyloid is necessary to induce tau aggregation. Interestingly, these tau immunoparticles accumulate in dendritic mitochondria in the APP/PS1 mice, whereas most of mitochondria in WT injected mice remain free of tau immunoparticles. Taken together, it seems that amyloid induces tau aggregation and accumulation in the dendritic mitochondria and subsequently may alter synapse function, thus, contributing to accelerate cognitive decline in APP/PS1 mice.We gratefully acknowledge grant funding support from Ministry of Science and Innovation (MINECO) with exp. PID2019-104921RB-I00/MCI/AEI/10.13039/501100011033 as well as to the Foundation for Applied Medical Research, the University of Navarra (Pamplona, Spain) for financial support and the Asociación de Amigos of the University of Navarra for the grant to M.P.-G. and S.B. We also gratefully acknowledge grant funding support from Spanish Ministerio de Economía y Competitividad (RTI2018-095812-B-I00 MCIN/ AEI/10.13039/501100011033) y por FEDER una manera de hacer Europa and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229) to RL, from the Spanish Ministry of Science Innovation and Universities (Ref. PID2019-110356RB-I00/AEI/10.13039/501100011033) to J.F.-I. and E.S and from the Department of Economic and Business Development from Government of Navarra (INNOLFACT project; Ref. 0011-1411-2020-000028)

Complicaciones patológicas de la menopausia

El objetivo del presente informe es formular, de acuerdo con la evidencia científica disponible y del juicio del panel de expertos convocados, los criterios generales que configuran conceptualmente el término "complicaciones patológicas de la menopausia" en orden a establecer recomendaciones prácticas que orienten su manejo diagnóstico y terapéutico.Presentación, Introducción, Definiciones y Cuestiones Planteadas Descripción de los Fenómenos Clínico-Biologicos Asociados a, o Coincidentes con la Menopausia, Técnicas y Procedimientos Diagnósticos Utilizados Para la Caracterización del Estado Biológico de la menopausia: Uso Apropiado, Intervenciones Preventivo-Terapéuticas: Beneficios y Riesgos, Medidas Generales, Terapia Hormonal Sustitutiva Otros Tratamientos, Selección de Grupos Potencialmente Beneficiarios de Intervenciones Terapéuticas, Conclusiones, Bibliografía, Abstrac

Small bowel enteroscopy - A joint clinical guideline from the spanish and portuguese small bowel study groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication and on its diagnostic and therapeutic yields. A set of recommendations were issued accordingly.Estas recomendações baseadas na evidência detalham o uso da enteroscopia assistida por dispositivo no manejo clínico das doenças do intestino delgado. Um conjunto de Gastrenterologistas diferenciados em patologia do intestino delgado foi selecionado pelos grupos de estudos Espanhol e Português de intestino delgado para rever a evidência disponível sobre as principais indicações desta técnica, o seu papel nos algoritmos de manejo de cada indicação e sobre o seu rendimento diagnóstico e terapêutico. Foi gerado um conjunto de recomendações pelos autores

Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database

Background: Studies have shown a slight excess risk in Guillain-Barre syndrome (GBS) incidence associated with A(H1N1) pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1) pdm09 vaccination. Methods: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. Results: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1) pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. Conclusions: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1) pdm09 monovalent or trivalent influenza immunisations, appears unlikely

Caracterización en la dinámica espacial de los macrohábitats acuáticos en la región de La Mojana

Con el fin de consolidar el levantamiento y análisis de la información sobre ecología en los humedales de La Mojana, este documento describe la biodiversidad asociada a las zonas de transición entre los principales macrohábitats acuáticos naturales identificados en esta región. Caracterizando por sectores desde la transición más húmeda hasta la más seca, identificando y caracterizando los micro-hábitats presentes dentro de cada uno de ellos e identificando la ocupación en el territorio por los distintos grupos biológicos.Bogotá, ColombiaPrograma Gestión Territorial de la Biodiversida

100 años investigando el mar. El IEO en su centenario (1914-2014).

Se trata de un libro que pretende divulgar a la sociedad las principales investigaciones multidisciplinares llevadas a cabo por el Instituto Español de Oceanografía durante su primer siglo de vida, y dar a conocer la historia del organismo, de su Sede Central y de los nueve centros oceanográficos repartidos por los litorales mediterráneo y atlántico, en la península y archipiélagos.Kongsberg 20

Diagnosis and therapeutic endoscopic management of mid-gastrointestinal bleeding = Manejo endoscópico diagnóstico y terapéutico de la hemorragia digestiva media

La hemorragia digestiva media (HDM) constituye la principal indicación de la cápsula endoscópica (CE) y la enteroscopia de doble balón (EDB). Ambos procedimientos se han demostrado de gran utilidad en estos pacientes alcanzando un rendimiento diagnóstico similar aunque hay factores que han demostrado afectar a la concordancia entre ambas pruebas. Así mismo, se ha descrito que la CE debería de ser la primera línea en la mayoría de los pacientes. Sin embargo, hay muchas situaciones específicas de HDM en las que no hay consenso en el papel de estas técnicas como la HDM manifiesta masiva y los tumores malignos de intestino delgado (TMID). En la presente tesis doctoral se recogen tres artículos que analizan la base de datos de pacientes del Hospital Morales Meseguer entre los años 2004-2014 en los que se realizó una CE y/o EDB por HDM, con especial énfasis en esclarecer la concordancia diagnóstica entre estas técnicas por tipo de lesión y su papel concreto en las situaciones descritas previamente. Aunque el nivel de acuerdo diagnóstico es similar entre la CE y EDB de forma global, esta puede variar notablemente para cada tipo de lesión. La concordancia diagnóstica entre CE y EDB según el tipo de lesión es alta en pólipos, lesiones vasculares y tumores. El nivel de acuerdo entre ambas es bajo en la lesión de Dieulafoy y en el sangrado sin lesión identificada.La EDB puede modificar el curso evolutivo de pacientes con TMID hasta en un 25% de los casos evitando o retrasando la cirugía. Este procedimiento permite identificar la localización tumoral y sus características, proporcionando información adicional que influye en su manejo posterior. Las lesiones vasculares y en particular la lesión de Dieulafoy situada habitualmente en ID proximal constituyen una de las casas más frecuentes de HDM manifiesta severa recurrente.La EDB urgente es un procedimiento efectivo en la HDM masiva, encontrando lesiones sugestivas de tratamiento endoscópico en la mayoría de los casos. El procedimiento combinado con CE en tiempo real se ha demostrado eficaz como primera línea, siendo especialmente útil para determinar el nivel de la hemorragia y orientar el abordaje posterior con EDB. Mid-gastrointestinal bleeding (MGIB) is the first indication of capsule endoscopy (CE) and double-balloon enteroscopy (DBE). Both procedures have demonstrated to be useful in these patients achieving a similar diagnostic yield. However, there are many factors that may influence the agreement between both procedures. In addition, CE should be administered as first-line in most of cases. However, there are many specific situations of MGIB in which there is no consensus about the role of these techniques, such as massive overt-MGIB and malignant small bowel tumors (MSBT). In the present thesis, three articles analyzed the Morales Meseguer Hospital database. Patients in whom a CE and/or DBE was carried out between 2004 and 2014 were considered, with focus on clarifying the diagnostic agreement by type of lesion of both techniques and its role in the previously described situations. Although the degree ofdiagnosticagreement is similarbetween the CE and DBE,thiscan vary significantlyforeach type of lesion.The diagnosis agreement between CE and DBE according to the type of lesion is high in polyps, vascular lesions and tumors. The degree of agreement between both is low for Dieulafoy’s lesion and bleeding without lesion identified.DBE may modify clinical outcome of patients with MSBT in up to 25% of cases by modifying or avoiding surgery. This procedure allows to identify the tumor location and characteristics, providing additional information that may influence further management. Vascular lesions and Dieulafoy’s lesion usually located in proximal small bowel are one of the most frequent causes of recurrent severe overt-MGIB.Emergency DBE is an effective procedure in massive MGIB, finding lesions amenable to endoscopic therapy in most of cases. Combined approach with real-time by CE has shown to be effective as fist-line, being especially useful to determine the level of the bleeding and guiding further DBE route