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

Effect of Hf on the growth of Al coatings onmartensite ferritic by means of CVD-FBR steels

RESUMEN: En las últimas décadas, ha habido un marcado interés por aumentar la temperatura y la presión de vapor en las plantas de generación de energía con el propósito de disminuir el consumo de combustibles. Así, se conseguiría reducir las emisiones de contaminantes tales como CO2, SO2 y NOx. Para lograr estas mejoras, se requiere por un lado desarrollar nuevos aceros ferríticos-martensíticos con contenidos de Cr entre 9-12% y por otro lado, mediante la ingeniería de superficies, mejorar la resistencia a la oxidación de los ya existentes. En el presente trabajo se obtuvieron recubrimientos de Al y de Al-Hf y evaluó el efecto de la adición del Hf al lecho sobre el crecimiento de los recubrimientos de Al. Previamente a la obtención de los recubrimientos, se realizó un estudio termodinámico mediante el programa Themocalc y, de acuerdo a los resultados obtenidos, se depositaron las capas de Al y Al-Hf a tres temperaturas diferentes en el rango de 500 a 600 ºC. Los recubrimientos fueron caracterizados mediante DRX y MEB/EDAX. De acuerdo con los resultados obtenidos se determinó que para ambos casos las capas estaban fundamentalmente formadas por los compuestos intermetálicos Fe2 Al5 y FeAl3.ABSTRACT: In recent decades, there has been a marked interest for increasing the temperature and vapor pressure in the power generation plants with the aim of reducing fuel consumption. So, there would be a reduction in the emissions of pollutants such as CO2, SO2 and NOx. To achieve these improvements, it is required on one hand, to develop new ferritic-martensitic steels with Cr contents between 9-12% and on the other hand, to improve resistance against oxidation of the existing ones by using surface engineering. For this reason, the following work is intended to obtain Al and Al-Hf coatings and evaluate the effect of the addition of Hf to the bed on the growth of the coating of Al. In order to optimize the deposition process, a thermodynamic study was conducted using Themocalc program. Al and Al-Hf layers were deposited at three different temperatures in the range of 500 to 600 º C. The coatings were subsequently characterized by DRX and SEM / EDS. According to the results, it was found that for both cases, the layers were mainly formed by intermetallic compounds Fe2 Al5 and FeAl3

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)

Detection of Biological CO2 and 1,3-Pentadiene Using Non-refrigerated Low-Cost MWIR Detectors

The early detection of spoiling metabolic products in contaminated food is a very important tool to control quality. Some volatile compounds produce unpleasant odours at very low concentrations, making their early detection very challenging. This is the case of 1,3-pentadiene produced by microorganisms through decarboxylation of the preservative sorbate. In this work, we have developed a methodology to use the data produced by a low-cost, compact MWIR (Mid-Wave IR) spectrometry device without moving parts, which is based on a linear array of 128 elements of VPD PbSe coupled to a linear variable filter (LVF) working in the spectral range between 3 and 4.6 ?m. This device is able to analyze food headspace gases through dedicated sample presentation setup. This methodology enables the detection of CO2 and the volatile compound 1,3-pentadiene, as compared to synthetic patrons. Data analysis is based on an automated multidimensional dynamic processing of the MWIR spectra. Principal component and discriminant analysis allow segregating between four yeast strains including producers and no producers. The segregation power is accounted as a measure of the discrimination quality

Dendronized Anionic Gold Nanoparticles: Synthesis, Characterization and Antiviral Activity

Anionic carbosilane dendrons decorated with sulfonate functions and with a thiol moiety at the focal point have been used to synthesize water soluble gold nanoparticles (AuNPs) by direct reaction of dendrons, gold precursor and reducing agent in water and also by place-exchange reaction. These nanoparticles have been characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), UV, elemental analysis, and Z potential. Also, the interacting ability of the anionic sulfonate functions was investigated by electron paramagnetic resonance (EPR) using copper(II) as a probe. It was found that the different structures and conformations of the AuNPs modulate the availability of sulfonate and thiol groups to be complexed by copper(II). Toxicity assays of AuNPs showed that those produced by direct reaction were less toxic than those obtained by ligand exchange. Inhibition of HIV-1 infection was higher for dendronized AuNPs than for dendrons.Ministerio de Economía y EmpresaComunidad de MadridUniversidad de Alcal

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Precariedad, exclusión social y modelo de sociedad: lógicas y efectos subjetivos del sufrimiento social contemporáneo (IV). Innovación docente en Filosofía

El PIMCD “Precariedad, exclusión social y modelo de sociedad: lógicas y efectos subjetivos del sufrimiento social contemporáneo (IV). Innovación docente en Filosofía” constituye la cuarta edición de un PIMCD que ha recibido financiación en las últimas convocatorias de PIMCD UCM, de los que se han derivado actividades de formación para estudiantes de Grado, Máster y Doctorado y al menos 3 publicaciones colectivas publicadas por Ediciones Complutense, Siglo XXI y Palgrave McMillan

Psicothema

Resumen tomado de la publicaciónEl objetivo de esta investigación ha sido analizar el mantenimiento de los efectos, tras un año de su finalización, de una intervención que integró 3 programas coordinados implementados con 27 niños con TDAH de 7 a 10 años, sus padres y sus profesores. La intervención tuvo una duración de 10 semanas e incluyó modificación de conducta, técnicas cognitivo-conductuales, adaptaciones académicas y habilidades sociales. Se valoraron los efectos sobre la adaptación académica, emocional y social a partir de informaciones aportadas por los padres, profesores y compañeros. Los resultados confirman el mantenimiento en la evaluación de seguimiento de las mejoras experimentadas tras el tratamiento, especialmente en las áreas académica y social, en las que estos niños presentaban las mayores dificultades.AsturiasColegio Oficial de Psicólogos de Asturias; Calle Ildefonso Sánchez del Río, 4-1 B; 33001 Oviedo; Tel. +34985285778; Fax +34985281374;Universidad de Oviedo. Facultad de Psicología; Plaza Feijoo, s. n.; 33003 Oviedo; Tel. +34985104146; Fax +34985104126;ES

Érase una vez : los artistas desde los principios

Esta innovación obtuvo un premio de la Consejería de Educación de la Comunidad de Madrid en 2003Este proyecto crea la posibilidad de que cada niño se transforme en un artista y exprese sus sentimientos. Se trabaja sobre las relaciones entre las primeras manifestaciones artísticas de la prehistoria y las primeras producciones plásticas del ser humano en sus primeros años de vida. Los objetivos son facilitar a los niños el acceso a distintas manifestaciones culturales artísticas de la época prehistórica y compararla con la actual; fomentar el respecto y la tolerancia hacia las personas y a la diversidad; conocer y valorar las normas y hábitos de comportamiento; comprender y expresar los mensajes mediante el lenguaje oral como medio de relación con los demás; utilización y comprensión de signos iconográficos diversos. Las actividades se dividen en actividades realizadas con los niños y las aquellas realizadas por las familias y equipo educativo. La metodología se basa en el principio de actividad, fomentando la creatividad, observación y experimentación. La evaluación de los niños se realiza a través de la observación directa; la exposición de trabajos de los propios niños que permita conocer la opinión de los otros niños al tiempo que les permite reflexionar sobre el trabajo de otros niños; anecdotarios. La evaluación de los adultos se lleva a cabo a través de la recogida de actividades en un diario con las actividades de los niños y otro con las actividades de los adultos, así como la realización de una encuesta a las familias al comienzo y al final del proyecto.Madrid (Comunidad Autónoma). Consejería de EducaciónMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES