Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

27 p.Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry and confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondriaJunta de Comunidades de Castilla-La Manch

A deletion at Adamts9-magi1 Locus is associated with psoriatic arthritis risk

Objective: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. Methods: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). Results: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). Conclusions: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk

Innovación del Diseño para el Desarrollo Social

Una labor de síntesis alrededor de la gran temática de este libro que surge a partir de una serie de reflexiones y propuestas encaminadas desde la innovación del diseño para el desarrollo social, refleja una invitación al lector para enunciar a partir de su lectura nuevas discusiones sobre el quehacer del diseño con una perspectiva de innovación para este tipo de desarrollo, es pues este texto una invitación a enunciar nuevos retos y diálogos partiendo de reconocer al desarrollo social como uno de los pilares fundamentales desde la Organización de las Naciones Unidas (ONU) como parte fundamental para garantizar el mejoramiento de la vida de las personas. Desde la disciplina del diseño y retomado como eje para su discusión se pretendería establecer una serie de reflexiones y acciones que permitan atender situaciones para grupos minoritarios y vulnerables, así como apoyar esfuerzos encaminados a mejorar la calidad de vida de los integrantes de grupos y sociedades establecidas y recuperar el patrimonio cultural como parte fundamental de las identidades culturales y por tanto de la historia de la humanidad.A lo largo de la historia, el diseño, en cualquiera de sus manifestaciones, ha estado presente en todos los ámbitos. Se ha convertido en una disciplina que evoluciona al ritmo de las sociedades, que se pone al servicio de las necesidades de mercado pero también de las que requieren un abordaje distinto, observadas desde una mirada que concierne a lo social, entendido éste como lo que se reproduce o se instaura en el colectivo, en el grupo, en las comunidades, en las sociedades como parte significativa de sus cotidianeidades. El Diseño desde esta perspectiva acompaña al ser humano produciendo una significación de los objetos como parte fundamental de sus vidas, que transforma una realidad deseada en una realidad concreta, de aquí la importancia de crear una conciencia social para la praxis laboral de esta disciplina. En este sentido el campo profesional, académico y de investigación del diseño debe ocuparse de crear, difundir y divulgar el quehacer de la misma, manifestando un equilibrio entre conciencia, racionalidad y la realidad. Desde el contexto planteado, la Universidad Autónoma del Estado de México, a través de su Facultad de Arquitectura y Diseño presenta en esta obra una serie de reflexiones en torno al papel que desempeña el diseño humanístico, científico y tecnológico desde un enfoque de vanguardia e innovación para el desarrollo social, como resultado de la experiencia vertida en el Coloquio Internacional de Diseño que organiza éste año este espacio académico, en donde cada una de las aportaciones refleja la experiencia de cada uno de sus participantes; con base en ello, el presente libro integrado por una compilación de trabajos ofrece descripciones, análisis y propuestas que contribuyen a la solución de problemas procurando un desarrollo social

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Extracción a nivel de documento de reacciones adversas a medicamentos en informes médicos electrónicos en español

Presentamos un sistema de extracción de Reacciones Adversas a Medicamentos (RAMs) para Informes Médicos Electrónicos escritos en español. El objetivo del sistema es asistir a expertos en farmacia cuando tienen que decidir si un paciente padece o no una o más RAMs. El núcleo del sistema es un modelo predictivo inferido de un corpus etiquetado manualmente, que cuenta con características semánticas y sintácticas. Este modelo es capaz de extraer RAMs de parejas enfermedad-medicamento en un informe dado. Finalmente, las RAMs extraídas automáticamente son post-procesadas usando un heurístico para presentar la información de una forma compacta. Esta fase ofrece los medicamentos y enfermedades del documento con su frecuencia, y también une las parejas relacionadas como RAMs. En resumen, el sistema no sólo presenta las RAMs en el texto sino que también da información concisa a petición de los expertos en farmacia (los usuarios potenciales del sistema).We outline an Adverse Drug Reaction (ADRs) extraction system for Electronic Health Records (EHRs) written in Spanish. The goal of the system is to assist experts on pharmacy in making the decision of whether a patient suffers from one or more ADRs. The core of the system is a predictive model inferred from a manually tagged corpus that counts on both semantic and syntactically features. This model is able to extract ADRs from disease-drug pairs in a given EHR. Finally, the ADRs automatically extracted are post-processed using a heuristic to present the information in a compact way. This stage reports the drugs and diseases of the document together with their frequency, and it also links the pairs related as ADRs. In brief, the system not only presents the ADRs in the text but also provides concise information on request by experts in pharmacy (the potential users of the system).This work was partially supported by the Spanish Ministry of Science and Innovation (EXTRECM: TIN2013-46616-C2-1-R) and the Basque Government (DETEAMI: Ministry of Health 2014111003, IXA Research Group of type A (2010-2015), Ber2Tek: IE12-333, Predoctoral Grant: PRE 2015 1 0211)

Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma

AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) by localized application into HepG2 tumor in vivo

Design and implementation of support and planning for 360º video recording: Video Recording techniques and problem solving derived from it

El objetivo principal del proyecto es potenciar las habilidades y capacidades de los alumnos mediante su involucración en proyectos relacionados con la práctica profesional y el espíritu de investigación, dentro de las áreas académicas pertenecientes a las Ciencias de la Información:Comunicación Audiovisual, Publicidad y Periodismo. En este sentido, los estudiantes desarrollan su potencial en un área, el entorno 360, en el que la industria se encuentra, en estos momentos, en una fase de búsqueda de soluciones que ofrezcan un producto satisfactorio no solo desde el punto de vista de su eficacia técnica y comunicativa, sino desde una perspectiva económica, esto es, del abaratamiento de costes.The main objective of the project is to enhance the skills and abilities of students through their involvement in projects related to professional practice and the spirit of research, within the academic areas belonging to the Communication Sciences: Audiovisual Communication, Advertising and Journalism. In this sense, students develop their potential in an area, the 360 ​​environment, in which the industry is currently in a phase of searching for solutions. It is important to offer a satisfactory product not only from the point of view of its technical and communicative efficiency, but from an economic perspective, that is, cost reduction.Depto. de Ciencias de la Comunicación AplicadaFac. de Ciencias de la InformaciónFALSEsubmitte

Anti-glomerular Basement Membrane Glomerulonephritis: A Study in Real Life.

Anti-glomerular basement membrane (anti-GBM) disease is a severe entity with few therapeutic options including plasma exchange and immunosuppressive agents. The aim of this study was to analyze the clinical and pathological features that predict the evolution of end-stage kidney disease (ESKD) and the kidney survival in a cohort of patients with anti-GBM disease with renal involvement in real life. A retrospective multicentre observational study including 72 patients from 18 nephrology departments with biopsy-proven anti-GBM disease from 1999 to 2019 was performed. Progression to ESKD in relation to clinical and histological variables was evaluated. Creatinine at admission was 8.6 (± 4) mg/dL and 61 patients (84.7%) required dialysis. Sixty-five patients (90.3%) underwent plasma exchange. Twenty-two patients (30.6%) presented pulmonary hemorrhage. Kidney survival was worse in patients with creatinine levels > 4.7 mg/dL (3 vs. 44% p 4.7 mg/dL (3 vs. 44% p 50% crescents (6 vs. 49%; p = 0.03). Dialysis dependence at admission and creatinine levels > 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25-7.84); HR 3 (1.01-9.14); p 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25-7.84); HR 3 (1.01-9.14); p 4.7 mg/dL and 50.5% crescents had an area under the curve (AUC) of 0.9 (95% CI 0.82-0.97; p In real life, patients with severe anti-GBM disease (creatinine > 4.7 mg/dL and > 50% crescents) remained with devastating renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies for the treatment of this rare renal disease are urgently needed