Mechanisms involved in the remyelinating effect of sildenafil

Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is. Using myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a MS model, we previously showed that daily administration of sildenafil starting at peak disease rapidly ameliorates clinical symptoms while administration at symptoms onset prevents disease progression. These beneficial effects of the drug involved down-regulation of adaptive and innate immune responses, protection of axons and oligodendrocytes (OLs) and promotion of remyelination. In this work we have investigated mechanisms involved in the remyelinating effect of sildenafil. Using demyelinated organotypic cerebellar slice cultures we demonstrate that sildenafil stimulates remyelination by direct effects on CNS cells in a nitric oxide (NO)-cGMP-protein kinase G (PKG)-dependent manner. We also show that sildenafil treatment enhances OL maturation and induces expression of the promyelinating factor ciliary neurotrophic factor (CNTF) in spinal cord of EAE mice and in cerebellar slice cultures. Furthermore, we demonstrate that sildenafil promotes a M2 phenotype in bone marrow derived macrophages (BMDM) and increases myelin phagocytosis in these cells and in M2 microglia/macrophages in the spinal cord of EAE mice. Taken together these data indicate that promotion of OL maturation directly or through induction of growth factor expression, regulation of microglia/macrophage inflammatory phenotype and clearance of myelin debris may be relevant mechanisms involved in sildenafil enhancement of remyelination in demyelinated tissue and further support the contention that this well tolerated drug could be useful for ameliorating MS pathology

Are quality regulations displacing PDOs? A choice experiment study on Iberian meat products in Spain

La publicación de la legislación española sobre normas de calidad que regula los productos cárnicos de cerdos ibéricos ha supuesto la certificación obligatoria del sistema de producción, piensos y raza en el sector porcino. El estándar está diseñado para garantizar la calidad del producto final, evitando los fraudes que pueden haberse producido anteriormente, aprovechando la heterogeneidad del producto. Tradicionalmente, las etiquetas de Denominación de Origen Protegida ofrecían la garantía y seguridad del consumidor, pero esta función ha sido asumida en gran medida por los Estándares de Calidad. En este contexto, es necesario estudiar el conocimiento de los consumidores y la valoración de estos dos indicadores de calidad. Se ha observado que, aunque los DOP son más conocidos que los estándares de calidad, los consumidores están dispuestos a pagar solo una pequeña prima por los productos ibéricos con un DOP. Por lo tanto, las PDO deben reorientarse para proporcionar un valor agregado al producto.The publication of the Spanish Quality Standards legislation regulating meat products from Iberian pigs has meant the obligatory certification of the system of production, feed, and breed in the Iberian pig sector. The Standard is designed to ensure the quality of the final product, avoiding the frauds that may have occurred previously taking advantage of the heterogeneity of the product. Traditionally, the Protected Designation of Origin labels offered the consumer guarantee and security, but this role has largely been taken over by the Quality Standards. In this context, there is a need to study consumers’ knowledge and valuation of these two quality indicators. It has been observed that, although PDOs are better known than the Quality Standards, consumers are willing to pay only a small premium for Iberian products with a PDO. Hence, PDOs need to be reoriented so as to provide added value to the product.peerReviewe

El proceso de una auditoría de cuentas anuales

Esta memoria detalla, de una manera teórico-práctica, las fases que se siguen a la hora de realizar un trabajo de auditoría de cuentas, a través de la visión de un auditor junior. De esta manera el lector podrá comprender el trabajo que un auditor realiza durante el transcurso completo de una auditoría. El proceso de auditoría de estados financieros comienza con la aceptación del encargo, tras ello se encuentra la fase de planificación, se sigue con la fase de ejecución, y finalizando con la propia emisión del informe de auditoría. El informe se encuentra respaldado por una evidencia suficiente y adecuada, obtenida a través de numerosos procedimientos realizados a lo largo de la auditoría. En esta memoria de fin de máster se incluyen anexadas la explicación de algunas de estas pruebas de auditoría comentadas desde una perspectiva práctica.<br /

Mechanisms Involved in the Remyelinating Effect of Sildenafil

Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is. Using myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a MS model, we previously showed that daily administration of sildenafil starting at peak disease rapidly ameliorates clinical symptoms while administration at symptoms onset prevents disease progression. These beneficial effects of the drug involved down-regulation of adaptive and innate immune responses, protection of axons and oligodendrocytes (OLs) and promotion of remyelination. In this work we have investigated mechanisms involved in the remyelinating effect of sildenafil. Using demyelinated organotypic cerebellar slice cultures we demonstrate that sildenafil stimulates remyelination by direct effects on CNS cells in a nitric oxide (NO)-cGMP-protein kinase G (PKG)-dependent manner. We also show that sildenafil treatment enhances OL maturation and induces expression of the promyelinating factor ciliary neurotrophic factor (CNTF) in spinal cord of EAE mice and in cerebellar slice cultures. Furthermore, we demonstrate that sildenafil promotes a M2 phenotype in bone marrow derived macrophages (BMDM) and increases myelin phagocytosis in these cells and in M2 microglia/macrophages in the spinal cord of EAE mice. Taken together these data indicate that promotion of OL maturation directly or through induction of growth factor expression, regulation of microglia/macrophage inflammatory phenotype and clearance of myelin debris may be relevant mechanisms involved in sildenafil enhancement of remyelination in demyelinated tissue and further support the contention that this well tolerated drug could be useful for ameliorating MS pathology

La metodología en el trabajo de huerto escolar y coherencia con la ambientalización curricular. Análisis de una práctica docente

This research introduces a case study of a primary school teacher who works with the school garden. It aims to know the degree of integration of sustainability in the teaching-learning process and the methodology carried out with the school garden. A series of indicators are designed for each of the proposed curricular background categories. In order to analyse the results we have used an interpretative qualitative methodology

The combination of crop diversification and no tillage enhances key soil quality parameters related to soil functioning without compromising crop yields in a low-input rainfed almond orchard under semiarid Mediterranean conditions

Soils provide key ecosystem services and are crucial to combat climate change. Agriculture provides important ecosystem services but also causes negative environmental effects depending on agricultural management. In this regard, crop diversification is a promising sustainable land management strategy to combat soil erosion and degradation, mitigate climate change and ensure food security. Here, we assess the combined short-term effects of crop diversification and no tillage on several key soil physico-chemical parameters related to soil functioning as well as on crop yields in a rainfed almond (Prunus dulcis Mill.) orchard under semiarid Mediterranean conditions. Almond trees were inter-cropped with Capparis spinosa L. (caper) or Thymus hyemalis Lange (winter thyme) and compared with the almond monocrop system. The experimental design consisted of three plots in a randomized-block design, with three replicates for each crop management treatment (almond monocrop, almond inter-cropped with caper, and almond inter-cropped with winter thyme). Along with crop yields, the combined effects of crop diversification and no tillage on a range of soil quality and health indicators including soil physical (bulk density, aggregate stability, water retention and availability) and chemical (total and particulate organic carbon and nitrogen, ammonium and nitrate content, available macro- and micro-nutrients) properties were monitored in the topsoil and subsoil (at 0–10 and 10–30 cm depth, respectively) one and three years from establishment.EEA Delta del ParanáFil: Almagro, María. Consejo Superior de Investigaciones Científicas (CSIC). Centro de Edafología y Biología Aplicada del Segura; EspañaFil: Díaz-Pereira, Elvira. Consejo Superior de Investigaciones Científicas (CSIC). Centro de Edafología y Biología Aplicada del Segura; EspañaFil: Boix-Fayos, Carolina. Consejo Superior de Investigaciones Científicas (CSIC). Centro de Edafología y Biología Aplicada del Segura; EspañaFil: Zornoza, Raúl. Universidad Politécnica de Cartagena. Departamento de Ingeniería Agronómica; EspañaFil: Sánchez-Navarro, Virginia. Universidad Politécnica de Cartagena. Departamento de Ingeniería Agronómica; EspañaFil: Re, Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Delta del Paraná; ArgentinaFil: Re, Paula. Universidad de Buenos Aires. Facultad de Agronomía; ArgentinaFil: Fernández, Cristina. Consejo Superior de Investigaciones Científicas (CSIC). Centro de Edafología y Biología Aplicada del Segura; EspañaFil: Martínez-Mena, María. Consejo Superior de Investigaciones Científicas (CSIC). Centro de Edafología y Biología Aplicada del Segura; Españ

Self-balanced two-output battery charger

The design and modeling of a self-balanced two-output battery charger capable to charge two high-power LiFePO4 battery packs is presented. The proposal is based on a four-phase resonant converter, which is designed as a voltage-controlled current-source, working at constant switching frequency. The output stage consists of a transformer with a single primary and two secondaries implementing two current-doubler rectifiers. The structure of the output stage naturally imposes the self-balance-of-charge of both battery packs provided that the coupling between the primary and each of the secondaries has a negligible mismatch. The electrical model of the battery is used to study the batteries charge equalization during the charging process considering the non-idealities of the output transformer. The theoretical analysis and design procedure of the proposed battery charger is fully explained. The output current capability and efficiency are validated experimentally considering a 50 Ah 48 V commercial battery pack.This work was supported by the Spanish Ministry of Science and Innovation and the European Commission under the research project PID2021-128941OB-I00 “Efficient Energy Transformation in IndustrialEnvironments

Improving the dynamic performance of bridgeless PFC controllers with zero crossing detector and root-mean-square calculation blocks

Bridgeless Power Factor Correctors (PFC) with a controller utilizing rectified ac variables can benefit from well-established strategies and circuits employed in PFCs with diode-bridge front-end. The grid voltage polarity is detected to compute the rms value of the grid voltage, and also used to generate and route the gate signals for the power devices. However, depending on the implementation, grid voltage disturbances may propagate through the polarity detection and RMS calculation stages, leading to a degradation of the input current and output voltage. This issue is addressed in this manuscript by investigating a single-phase bridgeless totem-pole (TP) PFC through simulation and proposing the replacement of the conventional implementation with a frequency-locked loop (FLL) to enhance the converter dynamics.This work has been partially supported by the Spanish Ministry of Science and Innovation under grant PID2021-128941-OB-100: “Efficient Energy Transformation in Industrial Environments” (TRENTI)

Diseño de alternativas de mejora de los tiempos de parada por el proceso de limpieza de tanques en la empresa Slenger S.A.

The Colombian industry is looking to generate a positive impact on the country's economy by implementing high standards of quality and competitiveness. This is the reason why the industrial processes must be efficient in improving dead times and waste. A lost of time in a process causes a waste of the capacity of the production, which then breaches strategic objectives and therefore it is necessary to incur in product shortages. Some of the events that cause different types of waste are corrective and preventive maintenance, stops due to damages, stops due to wastes and stops due to design changes of product references. Taking into account the mentioned above, in order to improve the efficiency of a process, it is necessary to focus on finding and eliminating factors that slow down the operation directly.Ingeniero (a) IndustrialPregrad