Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes

Background Both Alzheimer's disease (AD) and type 2 diabetes (T2D) share common pathological features including inflammation, insulin signaling alterations, or vascular damage. AD has no successful treatment, and the close relationship between both diseases supports the study of antidiabetic drugs to limit or slow down brain pathology in AD. Empagliflozin (EMP) is a sodium-glucose co-transporter 2 inhibitor, the newest class of antidiabetic agents. EMP controls hyperglycemia and reduces cardiovascular comorbidities and deaths associated to T2D. Therefore, we have analyzed the role of EMP at the central level in a complex mouse model of AD-T2D. Methods We have treated AD-T2D mice (APP/PS1xdb/db mice) with EMP 10 mg/kg for 22 weeks. Glucose, insulin, and body weight were monthly assessed. We analyzed learning and memory in the Morris water maze and the new object discrimination test. Postmortem brain assessment was conducted to measure brain atrophy, senile plaques, and amyloid-beta levels. Tau phosphorylation, hemorrhage burden, and microglia were also measured in the brain after EMP treatment. Results EMP treatment helped to maintain insulin levels in diabetic mice. At the central level, EMP limited cortical thinning and reduced neuronal loss in treated mice. Hemorrhage and microglia burdens were also reduced in EMP-treated mice. Senile plaque burden was lower, and these effects were accompanied by an amelioration of cognitive deficits in APP/PS1xdb/db mice. Conclusions Altogether, our data support a feasible role for EMP to reduce brain complications associated to AD and T2D, including classical pathological features and vascular disease, and supporting further assessment of EMP at the central level

Anal atresia in dogs and cats: the scope from three clinical cases

Anal atresia is defined as the lack of a complete communication between rectum and the anus, it is the most common anorectal malformation and has been observed mainly in dogs. It has been associated to alterations of anogenital differentiation of the cloaca in the embryo, however, the exact mechanisms remain unclear. Different criteria have been proposed in the literature to classify anal atresia. This study shows the diagnosis, treatment and outcome of three cases (two dogs and one cat) with anal atresia. The frequency of this malformation in our hospital is reported as well as a discussion of the theories of the processes involved in the development of anal atresia, and a revised classification for this pathology according to embryo anatomy and development is proposed.La atresia anal se define como la falta de comunicación del recto y el perineo a través del ano, siendo esta la malformación anorrectal reportada con mayor frecuencia en el perro y el gato. Está asociada a alteraciones en la diferenciación de la cloaca en el embrión en desarrollo; sin embargo los mecanismos fisiopatológicos involucrados hasta el momento no han sido completamente esclarecidos. En el presente documento se expone la experiencia en el diagnóstico y manejo de tres pacientes (dos perros y un gato) con atresia anal, presentamos los resultados del análisis de la frecuencia de esta patología en nuestro centro hospitalario, realizamos una revisión detallada de las teorías de los mecanismos fisiopatológicos involucrados en el desarrollo embrionario y con base en estos criterios, sugerimos la clasificación del tipo de atresia anal más apropiada partiendo del análisis de las propuestas existentes y su relación con los conceptos actuales de la anatomía embriológica.Al Consejo Nacional de Ciencia y Tecnología de México (CONACyT) por el esquema de becas para los alumnos en el Programa de Especialización en Medicina y Cirugía en Perros y Gatos de la Facultad de Medicina Veterinaria y Zootecnia de la Universidad Autónoma del Estado de México, inserto en el Padrón Nacional de Excelencia-CONACyT

Alzheimer's Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models

Alzheimer's disease (AD) is the most common cause of dementia. Epidemiological studies show the association between AD and type 2 diabetes (T2DM), although the mechanisms are not fully understood. Dietary habits and lifestyle, that are risk factors in both diseases, strongly modulate gut microbiota composition. Also, the brain-gut axis plays a relevant role in AD, diabetes and inflammation, through products of bacterial metabolism, like short-chain fatty acids. We provide a comprehensive review of current literature on the relation between dysbiosis, altered inflammatory cytokines profile and microglia in preclinical models of AD, T2DM and models that reproduce both diseases as commonly observed in the clinic. Increased proinflammatory cytokines, such as IL-1 beta and TNF-alpha, are widely detected. Microbiome analysis shows alterations in Actinobacteria, Bacteroidetes or Firmicutes phyla, among others. Altered alpha- and beta-diversity is observed in mice depending on genotype, gender and age; therefore, alterations in bacteria taxa highly depend on the models and approaches. We also review the use of pre- and probiotic supplements, that by favoring a healthy microbiome ameliorate AD and T2DM pathologies. Whereas extensive studies have been carried out, further research would be necessary to fully understand the relation between diet, microbiome and inflammation in AD and T2DM

Production yields at the distal fall-off of the β+ emitters 11C and 13N for in-vivo range verification in proton therapy

In proton therapy, Positron Emission Tomography (PET) range verification relies on the comparison of the measured and estimated activity distributions from β+ emitters produced by the proton beam in the patient. The accuracy of the estimated activity distributions is basically that of the underlying reaction cross section data. In this context, we have developed a new method for measuring β+ production yields combining the multi-foil technique with a clinical PET scanner, resulting in energy differential cross sections from a single irradiation. The method has been applied to the production of (t1/2 = 20.36 min) and (t1/2 = 9.97 min), the main candidates for off-line PET range verification, in carbon, nitrogen and oxygen, the main elements of the human body. The energy range studied with the 18 MeV CNA cyclotron corresponds to the distal fall-off of the activity curve, i.e. near the Bragg peak.Ministerio de Economía y Competitividad RYC-2014-15271, FPA2016- 77689-C2-1-R, RTI2018-098117-B-C2

Escenarios de cambio climático regional en Cantabria aplicados a la cartografía agroclimática de precisión

RESUMEN: Se han elaborado para la CC.AA. de Cantabria los modelos climáticos regionales y los escenarios de cambio climático para el presente siglo con una precisión de “pixel” de 1Km, como producto de la interpolación de los datos meteorológicos al territorio a través de un SIG. Para la elaboración de dichos modelos se ha aplicado un método lineal local (regresión multivariada utilizando un conjuntode vecinos de cada punto), considerando como regresores las siguientes variables: elevación sobre el nivel del mar, su cuadrado y su cubo, longitud y latitud, insolación potencial en cinco épocas distintas del año, distancia a la costa, su cuadrado y su cubo, curvatura, calculada con radios de 5, 10 y 25 km, vertical y horizontal, y orientación, según la dirección de ocho cuadrantes. Con esta información se obtuvo el Mapa de tipos o zonas agroclimáticas de Papadakis con resolución 1x1 km. Finalmente, se ha obtenido la evolución del Mapa Agroclimático a lo largo de cuatro períodos temporales 1971– 2000, 2011–2040 y 2041–2070 y 2071–2100. Todos los procesos de cálculo están automatizados, pudiéndose generarse resultados a partir de actualizaciones o nuevos datos.ABSTRACT: Through the interpolation of meteorological data on a Geographic Information System (GIS), regional climate models (at 1 km spatial resolution) and scenarios of climate change for this century have been developed for the Cantabria Region. For the development of those models a local liner method has been used (multivariate regression using a set of neighbours at each point) considering the following variables: altitude, its square and cube, longitude, latitude, potential insolation, distance from the coast, its square and cube, topographic barriers and aspect. With this information zoning of Cantabria and the Papadakis’s Agro–climatic Map have been obtained. Finally, the evolution of the Agro–climatic Map and the potential for the selected crops have been obtained for four time periods: 1971–2000, 2011–2040, 2041–2070 and 2071–2100. GIS procedures make up to date possible when new data is available or refinements desired

Desarrollo Económico de la Comarca de Cartagena 2016

El presente informe tiene la finalidad de servir como una herramienta de diagnóstico de la situación económica del tejido empresarial de la Comarca de Cartagena, promoviendo medidas que contribuyen al desarrollo estratégico de la Comarca. A partir del estudio y análisis del contexto socioeconómico sectorial que han realizado los investigadores especialistas en cada uno de los sectores de actividad, así como del análisis por parte de los paneles de expertos consultados, se incluye a continuación un estudio por sectores de actividad de las actuaciones que deberían considerarse para establecer las líneas estratégicas de contenido económico en la Comarca de Cartagena en los próximos años. Las políticas que permitan desarrollar dichas actuaciones asegurarán la competitividad de las pequeñas y medianas empresas en general y el adecuado progreso económico de la Comarca en particular. Los principales pilares de competitividad sobre los que deberían asentarse las actuaciones estratégicas para la comarca se han clasificado por sectores de actividad atendiendo a las infraestructuras, el conocimiento (formación y cualificación), el desarrollo de las tecnologías de la información y las comunicaciones, la innovación, la financiación y la eficiencia de las Administraciones Públicas. El informe se estructura en una primera aproximación a la situación macroeconómica de la Comarca en su contexto Regional y Nacional desde el punto de vista de la oferta y la demanda, así como un detalle prospectivo de la economía para los próximos meses. A continuación se detalla el análisis sectorial dividido en los sectores: turismo, comercio, industria, agroalimentación y tecnológico. Adicionalmente, se incluye un análisis y diagnóstico económicofinanciero a nivel microeconómico de las pymes de la Comarca. Por último, se incluyen a modo de resumen las principales conclusiones y recomendaciones derivadas del estudi

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Desarrollo de herramientas críticas e instrumentales y diseño de recursos educativos en abierto en torno al cómic

El cómic funciona como hilo conductor temático del proyecto, empleando las nuevas tecnologías y la teoría crítica de manera instrumental. cuenta con una triple vertiente: formación de estudiantes, formación de docentes y futuros docentes, y transferencia de resultados. Esta triple vertiente se desarrolla a través de tres ejes: (1) Club de lectura de cómic autogestionado por estudiantes, bajo el título «Narrativas éticas para repensar el mundo»; (2) Talleres instrumentales, teoría crítica y empleabilidad para estudiantes del club y el resto de la comunidad universitaria y un encuentro con una autora; (3) Realización de contenidos en abierto —podcasts,— con los resultados del aprendizaje en los ejes (1) y (2)

The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

SeqCOVID-Spain consortium: Álvaro Chiner-Oms, Irving Cancino-Muñoz, Mariana G. López, Manuela Torres-Puente, Inmaculada Gómez-Navarro, Santiago Jiménez-Serrano, Jordi Pérez-Tur, Darío García de Viedma, Laura Pérez-Lago, Marta Herranz, Jon Sicilia, Pilar Catalán-Alonso, Julia Suárez González, Patricia Muñoz, Mireia Coscolla, Paula Ruiz-Rodríguez, Fernando González-Candelas, Iñaki Comas, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Llúcia Martínez Priego, Inmaculada Galán-Vendrell, Paula Ruiz-Hueso, Griselda De Marco, María Loreto Ferrús-Abad, Sandra Carbó-Ramírez, Giuseppe D’Auria, Galo Adrian Goig, Juan Alberola, Jose Miguel Nogueira, Juan José Camarena, David Navarro, Eliseo Albert, Ignacio Torres, Maitane Aranzamendi Zaldumbide, Óscar Martínez Expósito, Nerea Antona Urieta, María de Toro, María Pilar Bea-Escudero, Jose Antonio Boga, Cristian Castelló-Abietar, Susana Rojo-Alba, Marta Elena Álvarez-Argüelles, Santiago Melón, Elisa Martró, Antoni E. Bordoy, Anna Not, Adrián Antuori, Anabel Fernández-Navarro, Andrés Canut-Blasco, Silvia Hernáez Crespo, Maria Luz Cordón Rodríguez, Maria Concepción Lecaroz Agara, Carmen Gómez-González, Amaia Aguirre-Quiñonero, José Israel López-Mirones, Marina Fernández-Torres, Maria Rosario Almela-Ferrer, Ana Carvajal, Juan Miguel Fregeneda-Grandes, Héctor Argüello, Gustavo Cilla Eguiluz, Milagrosa Montes Ros, Luis Piñeiro Vázquez, Ane Sorarrain, José María Marimón, José J. Costa-Alcalde, Rocío Trastoy, Gema Barbeito Castiñeiras, Amparo Coira, María Luisa Pérez del Molino, Antonio Aguilera, Begoña Palop-Borrás, Inmaculada de Toro Peinado, Maria Concepción Mediavilla Gradolph, Mercedes Pérez-Ruiz, Mirian Fernández-Alonso, Jose Luis del Pozo, Oscar González-Recio, Mónica Gutiérrez-Rivas, Jovita Fernández-Pinero, Miguel Ángel Jiménez Clavero, Begoña Fuster Escrivá, Concepción Gimeno Cardona, María Dolores Ocete Mochón, Rafael Medina-Gonzalez, José Antonio Lepe, Verónica González Galán, Ángel Rodríguez-Villodres, Nieves Gonzalo Jiménez, Jordi Reina, Carla López-Causapé, Maria Dolores Gómez-Ruiz, Eva M. Gonzalez-Barbera, José Luis López-Hontangas, Vicente Martín, Antonio J. Molina, Tania Fernandez-Villa, Ana Milagro Beamonte, Nieves Felisa Martínez-Cameo, Yolanda Gracia-Grataloup, Rosario Moreno-Muñoz, Maria Dolores Tirado Balaguer, José María Navarro-Marí, Irene Pedrosa-Corral, Sara Sanbonmatsu-Gámez, Antonio Oliver, Mónica Parra Grande, Bárbara Gómez Alonso, Francisco José Arjona Zaragozí, Maria Carmen Pérez González, Francisco Javier Chamizo López, Ana Bordes-Benítez, Núria Rabella, Ferran Navarro, Elisenda Miró, Antonio Rezusta, Alexander Tristancho, Encarnación Simarro Córdoba, Julia Lozano-Serra, Lorena Robles Fonseca, Álex Soriano, Francisco Javier Roig Sena, Hermelinda Vanaclocha Luna, Isabel Sanmartín, Daniel García-Souto, Ana Pequeño-Valtierra, Jose M. C. Tubio, Javier Temes, Jorge Rodríguez-Castro, Martín Santamarina García, Manuel Rodríguez-Iglesias, Fátima Galán-Sanchez, Salud Rodríguez-Pallares, José Manuel Azcona-Gutiérrez, Miriam Blasco-Alberdi, Alfredo Mayor, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobaño, Pau Cisteró, Oriol Mitjà, Camila González-Beiras, Martí Vall-Mayans, Marc Corbacho-Monné, Andrea Alemany, Cristina Muñoz-Cuevas, Guadalupe Rodríguez-Rodríguez, Rafael Benito, Sonia Algarate, Jessica Bueno, Andrea Vergara-Gómez, Miguel J. Martínez, Jordi Vila, Elisa Rubio, Aida Peiró-Mestres, Jessica Navero-Castillejos, David Posada, Diana Valverde, Nuria Estévez, Iria Fernández-Silva, Loretta de Chiara, Pilar Gallego-García, Nair Varela, Ulises Gómez-Pinedo, Mónica Gozalo-Margüello, Maria Eliecer Cano García, José Manuel Méndez-Legaza, Jesus Rodríguez-Lozano, María Siller, Daniel Pablo-Marcos, Maria Montserrat Ruiz-García, Antonio Galiana, Judith Sánchez-Almendro, Maria Isabel Gascón Ros, Cristina Juana Torregrosa-Hetland, Eva María Pastor Boix, Paloma Cascales Ramos, Pedro Luis Garcinuño Enríquez, Salvador Raga Borja, Julia González Cantó, Olalla Martínez Macias, Adolfo de Salazar, Laura Viñuela González, Natalia Chueca, Federico García, Cristina Gómez-Camarasa, Amparo Farga Martí, Rocío Falcón, Victoria Domínguez-Márquez, Anna M. Planas, Israel Fernández-Cádenas, Maria Ángeles Marcos, Carmen Ezpeleta, Ana Navascués, Ana Miqueleiz Zapatero, Manuel Segovia, Antonio Moreno-Docón, Esther Viedma, Raúl Recio Martínez, Irene Muñoz-Gallego, Sara Gonzalez-Bodi, Maria Dolores Folgueira, Jesús Mingorance, Elias Dahdouh, Fernando Lázaro-Perona, María Rodríguez-Tejedor, María Pilar Romero-Gómez, Julio García-Rodríguez, Juan Carlos Galán, Mario Rodríguez-Dominguez, Laura Martínez-García, Melanie Abreu Di Berardino, Manuel Ponce-Alonso, Jose Maria González-Alba, Ivan Sanz-Muñoz, Diana Pérez San José, Maria Gil Fortuño, Juan B. Bellido-Blasco, Alberto Yagüe Muñoz, Noelia Hernández Pérez, Helena Buj Jordá, Óscar Pérez Olaso, Alejandro González Praetorius, Nora Mariela Martínez Ramírez, Aida Ramírez Marinero, Eduardo Padilla León, Alba Vilas Basil, Mireia Canal Aranda, Albert Bernet Sánchez, Alba Bellés Bellés, Eric López González, Iván Prats Sánchez, Mercè García-González, Miguel José Martínez-Lirola, Manuel Ángel Rodríguez Maresca, Maria Teresa Cabezas Fernández, María Eugenia Carrillo Gil, Maria Paz Ventero Martín, Carmen Molina Pardines, Nieves Orta Mira, María Navarro Cots, Inmaculada Vidal Catalá, Isabel García Nava, Soledad Illescas Fernández-Bermejo, José Martínez-Alarcón, Marta Torres-Narbona, Cristina Colmenarejo, Lidia García-Agudo, Jorge A. Pérez García, Martín Yago López, María Ángeles Goberna Bravo, Victoria Simón García, Gonzalo Llop Furquet, Agustín Iranzo Tatay, Sandra Moreno-Marro, Noelia Lozano Rodríguez, Amparo Broseta Tamarit, Juan José Badiola Díez, Amparo Martínez-Ramírez, Ana Dopazo, Sergio Callejas, Alberto Benguría, Begoña Aguado, Antonio Alcamí, Marta Bermejo Bermejo, Ricardo Ramos-Ruíz, Víctor Manuel Fernández Soria, Fernando Simón Soria & Mercedes Roig CardellsThe coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.This work was mainly funded by the Instituto de Salud Carlos III project COV20/00140, with additional funding by Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia project PID2019-104477RB-100, ERC StG 638553 and ERC CoG 101001038 to I.C., and BFU2017-89594R to F.G.C. M.C. is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and Generalitat Valenciana (Regional Government) project SEJI/2019/011. We gratefully acknowledge Hospital Universitari Vall d’Hebron, Instituto de Salud Carlos III, IrsiCaixa AIDS Research Lab and all the international researchers and institutions that submitted sequenced SARS-CoV-2 genomes to the GISAID’s EpiCov Database (Supplementary Table 1), as an important part of our analyses has been made possible by the sharing of their work. We also thank Unidad de Bioinformática y Estadística, Centro de Investigación Príncipe Felipe, for allowing us to use the Computer Cluster to perform some of the bioinformatic analysis.Peer reviewe