Mitochondrial activity is modulated by TNFα and IL-1β in normal human chondrocyte cells

SummaryObjectivePro-inflammatory cytokines play an important role in osteoarthritis (OA). In osteoarthritic cartilage, chondrocytes exhibit an alteration in mitochondrial activity. This study analyzes the effect of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) on the mitochondrial activity of normal human chondrocytes.Materials and methodsMitochondrial function was evaluated by analyzing the activities of respiratory chain enzyme complexes and citrate synthase, as well as by mitochondrial membrane potential (Δψm) and adenosine triphosphate (ATP) synthesis. Bcl-2 family mRNA expression and protein synthesis were analyzed by RNase protection assay (RPA) and Western-blot, respectively. Cell viability was analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and apoptosis by 4′, 6-diamidino-2-phenylindole dihydrochloride (DAPI) stain. Glycosaminoglycans were quantified in supernatant by a dimethyl-methylene blue binding assay.ResultsCompared to basal cells, stimulation with TNFα (10ng/ml) and IL-1β (5ng/ml) for 48h significantly decreased the activity of complex I (TNFα=35% and IL-1β=35%) and the production of ATP (TNFα=18% and IL-1β=19%). Both TNFα and IL-1β caused a definitive time-dependent decrease in the red/green fluorescence ratio in chondrocytes, indicating depolarization of the mitochondria. Both cytokines induced mRNA expression and protein synthesis of the Bcl-2 family. Rotenone, an inhibitor of complex I, caused a significant reduction of the red/green ratio, but it did not reduce the viability of the chondrocytes. Rotenone also increased Bcl-2 mRNA expression and protein synthesis. Finally, rotenone as well as TNFα and IL-1β, reduced the content of proteoglycans in the extracellular matrix of normal cartilage.ConclusionThese results show that both TNFα and IL-1β regulate mitochondrial function in human articular chondrocytes. Furthermore, the inhibition of complex I by both cytokines could play a key role in cartilage degradation induced by TNFα and IL-1β. These data could be important for understanding of the OA pathogenesis

El rol de la educación en materia de discriminación derivada de factores étnicos y religiosos

Plantear el rol de la educación en materia de discriminación derivada de factores étnicos y religiosos nos conduce necesariamente a afirmar la igualdad en la diferencia: la Dignidad Humana.Sabemos que todos los seres humanos somos diferentes, sexo, edad, religión, nacionalidad, profesión, nivel educativo etc. sin embargo por encima de cualquier diferencia, todas las personas somos iguales en nuestra naturaleza humana; por el solo hecho de ser personas somos merecedores (dignos) de gozar de características que conforman la dignidad humana. En la actualidad la dignidad humana es la base sobre la que se construye la justicia y el derecho, o sea, que solo por pertenecer a la especie humana nos corresponde gozar de derechos y justicia. Este principio está protegido constitucionalmente en el artículo dieciséis “…todos los habitantes son iguales ante la ley…”.No obstante, sabemos que la convivencia presenta conflictos, las sociedades asisten con frecuencia a conflictos entre sus miembros que van desde las guerras hasta las persecuciones políticas, religiosas o raciales. Muchos de estos conflictos se producen sobre la base de una actitud de discriminación, que se genera cuando se utilizan las diferencias existentes entre las personas para afirmar la superioridad de unas sobre otras. La discriminación origina situaciones de desigualdad. La Universidadcomo ámbito de estudio, reflexión y de formación de profesionales, y más aun nuestra Universidad Católica debe fortalecer a través de los procesos de formación de sus alumnos los principios de promoción y defensa de la dignidad humana. La eliminación de toda forma de discriminación, especialmente la discriminación de género, étnica y racial, y de las diversas formas de intolerancia, así como la promoción y protección de los derechos humanos de los pueblos indígenas y los inmigrantes y el respeto a la diversidad étnica, cultural y religiosa en las Américas, contribuyen al fortalecimiento de la democracia y la participación ciudadana. (Dulitzky Ariel, 2006).Por lo anteriormente analizado es que desde este proyecto de investigación nos vamos a posicionar desde la perspectiva intercultural, ya que consideramos que esta conceptualización es superadora en relación al concepto de muticulturalidad, y contribuyen a combatir la discriminación y la intolerancia religiosa y racial. La perspectiva  intercultural pone énfasis en el terreno de la interacción entre sujetos o entidades culturales diferenciados. El núcleo de la novedad interculturalista se halla en proponer algo sustantivo sobre el deber ser de las relaciones interétnicas, más allá de que no deben ser relaciones no discriminatorias entre iguales y basadas en el respeto y las tolerancia.

Long term clinical outcomes in survivors after out-of-hospital cardiac arrest

Introduction and objectives: Information regarding long-term outcomes in patients surviving out-of-hospital cardiac arrest (OHCA) is scarce. Our aim was to study the long-term clinical outcomes of a large cohort of OHCA patients surviving until hospital discharge and to identify predictors of mortality and cardiovascular events. Methods: Consecutive OHCA patients admitted in the Acute Cardiac Care Unit who survived at least until hospital discharge between 2007 and 2019 were included. All received therapeutic hypothermia according to the local protocol. Pre- and intra-hospital clinical and analytical variables were analyzed, as well as the clinically relevant events during follow-up. Results: A total of 201 patients were included, with a mean age of 57.6 ± 14.2 years, 168 (83.6%) were male. Thirty-six (17.9%) died during a median follow-up of 40.3 months (18.9–69.1), the most frequent causes of death being cardiovascular and neurological, followed by cancer. We calculated a predictive model for mortality during follow-up using Cox regression that included the following variables: poor neurological outcome [HR 3.503 (1.578–7.777)], non-shockable rhythm [HR 2.926 (1.390–6.163)], time to onset of CPR [HR 1.063 (0.997–1.134)], older age [1.036 (1.008–1.064)) and worse ejection fraction at discharge [1.033 (1.009–1.058)]. Conclusions: Even though few patients experience recurrent cardiac arrest events, survivors after OHCA face high morbidity and mortality during long-term follow-up. Therefore, they may benefit from multidisciplinary teams providing an integral management and ensuring continuity of car

MOOC as a Way of Dissemination, Training and Learning of Telecommunication Engineering

In this chapter, the use of massive open online courses (MOOCs) for the dissemination, training capabilities and learning of telecommunication engineering is described taking as example the successful MOOC ‘Ultra- Dense Networks for 5G and its Evolution’ developed under the European innovative training network (ITN) TeamUp5G. MOOCs are usually understood as a way of teaching or learning for massive potential students. Indeed, this is the main goal of any MOOC. However, we also propose its use for training and dissemination. The ITN TeamUp5G is a training network for 15 PhD students of seven different institutions (universities and companies) where the students make research on different interconnected topics for the common goal of Ultra dense networks for 5G. At the same time they researched, they prepared a MOOC to disseminate their most recent advances and their challenges. For the MOOC, they needed to collect their thoughts, organizse their knowledge and establish a common vision of the whole system. The cooperative work, the cross-related meetings and, the preparation of all the materials for the MOOC were very interesting and useful in their training process. The whole experience of designing and creating the MOOC is described in detail along with the challenges and lessons learned.info:eu-repo/semantics/acceptedVersio

Implementation of the Random Forest Method for the Imaging Atmospheric Cherenkov Telescope MAGIC

The paper describes an application of the tree classification method Random Forest (RF), as used in the analysis of data from the ground-based gamma telescope MAGIC. In such telescopes, cosmic gamma-rays are observed and have to be discriminated against a dominating background of hadronic cosmic-ray particles. We describe the application of RF for this gamma/hadron separation. The RF method often shows superior performance in comparison with traditional semi-empirical techniques. Critical issues of the method and its implementation are discussed. An application of the RF method for estimation of a continuous parameter from related variables, rather than discrete classes, is also discussed.Comment: 16 pages, 8 figure