Na+-H+ exchange activity in brush-border membrane vesicles isolated from chick small intestine

This study was undertaken to investigate the presence of a Na+{single bond}H+ antiporter in brush-border membrane vesicles (BBMV) isolated from chick small intestine. An outwardly directed proton gradient (pH 5.5 inside, 7.5 outside) stimulated Na+ uptake into BBMV and resulted in a transient accumulation. No accumulation was observed in the absence of a proton gradient. Voltage clamping the membrane with K+ and valinomycin decreased the Na+ overshoot. Amiloride inhibited pH gradient-driven Na+ uptake in a dose-dependent manner with an IC50 of 44 μM. The relationship between pH gradient-driven Na+ uptake and external Na+ concentration followed simple, saturating Michaelis-Menten kinetics. Eadie-Hofstee analysis of the pH gradient-driven Na+ uptake indicated a single transport system with a Vmax of 33 nmol/mg protein per 15 s and a Km for Na+ of 12 mM. The initial rate of pH-driven Na+ uptake increased as the intravesicular pH decreased, with a Hill coefficient close to 1. These findings indicate that BBMV isolated from chicken small intestine posses a Na+{single bond}H+ exchanger. This exchanger does not appear to be the one involved in cell pH regulation.Dirección General de Investigaciones Científicas y Técnicas PB89-061

Los incentivos fiscales a la inversión privada en el impuesto sobre sociedades. Especial referencia al País Vasco

La gran funcionalidad de la variable inversión justifica el empeño de las autoridades económicas por implementar medidas que traten de influir en su volumen, su composición, o en su localización. Nuestro trabajo tiene como finalidad estudiar si es posible que los instrumentos fiscales puedan desempeñar un papel de estímulo a la inversión o lo que es equivalente, analizaremos si es posible una relación fiscalidad-inversión. Nos hemos centrado en el Impuesto sobre Sociedades puesto que desde la óptica de las decisiones empresariales de producción, inversión, financiación o empleo es el más relevante, con efectos más rápidos y penetrantes en los diferentes sectores de la economía. Además la política de incentivación fiscal se ha venido concretando, especialmente, a través de este impuesto, dadas las posibilidades que ofrece vía gastos fiscalmente deducibles, deducciones en la cuota, exenciones, o alteración en el tipo de gravamen. Nosotros hemos utilizado los incentivos fiscales más habituales en los códigos fiscales de los países industrializados. Las peculiaridades entre el País Vasco y el resto del Estado en la aplicación de los incentivos nos lleva a estudiar, al menos brevemente, la normativa vasca

Realización de vídeo de enseñanza online y presencial para prácticas por internet y presenciales de la radiografía de muñeca como método para valorar el desarrollo óseo

Se ha realizado un video en el que el alumno visualiza los diferentes estadios de desarrollo que tienen lugar en la osificación de la muñeca y puede aprender cómo utilizar la radiografía de muñeca para determinar el momento de desarrollo del paciente

Análisis de los niveles de lactato en salvamento y socorrismo a través del diseño de un test específico para 100m socorrista (estudio piloto)

Antecedentes: El análisis de lactato en alto rendimiento es fundamental para planificar el entrenamiento de forma eficiente e individualizada, sin embargo no contamos con protocolos específicos para salvamento y socorrismo. Objetivos: i) Diseñar un protocolo específico de valoración del lactato para la prueba 100m socorrista; ii) Conocer los niveles de lactato en socorristas especializadas en pruebas de aletas; iii) Proporcionar una herramienta de valoración específica que permita establecer pautas fisiológicas de control del entrenamiento. Método: Para ello se diseñó un test progresivo específico consistente en: 5 repeticiones de 100m remolque de maniquí con aletas y tubo con descansos de entre 1 y 2 minutos. Dicho test fue realizado por 6 deportistas de categoría femenina de entre 17 y 21 años. Resultados: Los resultados no se corresponden con los esperados para este tipo de tests. Conclusiones: i) Ante la falta de estudios fisiológicos en salvamento y socorrismo se hace necesario diseñar protocolos que puedan establecer patrones analizables y trasladables a las sesiones de entrenamiento; ii) El diseño de pruebas de valoración de carácter aeróbico utilizando material específico es esencial para poder trasladar los resultados a contenidos de entrenamiento; iii) Los resultados obtenidos por las deportistas en el test no concuerdan con los esperados, lo que podría deberse a la incorrecta realización del test en cuanto a sus velocidades de ejecución, a la falta de experiencia de los sujetos analizados o al incorrecto planteamiento del test en relación a los descansos o las repeticiones planificad

Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN) in relation to the possible risk of dietary aluminium

El Comité Mixto FAO/OMS de Expertos en Aditivos Alimentarios (JECFA) en 2006 tuvo en cuenta los efectos que algunos compuestos de Aluminio inducían sobre la reproducción y sobre el desarrollo del sistema nervioso, y redujo la Ingesta Semanal Tolerable Provisional (PTWI) del Al de 7 mg Al/kg pc/semana a 1 mg Al/kg pc/semana. Esta reducción ha sido asumida posteriormente por la Autoridad Europea de Seguridad Alimentaria (EFSA, 2008a, 2008b), que emitió una opinión científica sobre la seguridad de la ingesta de aluminio a través de la dieta, en la que se estima que una parte importante de la población europea puede superar el nivel seguro establecido. La exposición dietética en adultos no expuestos ocupacionalmente a Al muestra una gran variación entre los distintos países, e incluso, en un mismo país. Así, EFSA informa que la exposición por consumo de agua y alimentos en adultos con un peso medio de 60 kg oscila entre 0,2-1,5 mg Al/kg pc/ semana, estimándose que en niños y jóvenes la exposición dietética al percentil 97,5 en algunos países (Reino Unido y Francia) es 0,7-2,3 mg Al/kg pc/semana. Los estudios disponibles no permiten conocer las fuentes dietéticas concretas de Al, ni la diferenciación entre los distintos orígenes del Al que incluyen el intrínseco, el procedente de aditivos alimentarios y el resultante de los procesos de elaboración y almacenamiento de los alimentos. Los contenidos de Al de alimentos analizados en diferentes países europeos muestran una variabilidad relativamente elevada, incluso entre los componentes de un mismo grupo. El Comité Científico de la AESAN considera adecuado el nuevo umbral de seguridad establecido por la EFSA de ingesta de 1 mg Al/kg pc/semana. El Comité destaca la escasez de datos acerca del contenido de Al en alimentos en nuestro país. Los elevados contenidos de Al encontrados en algunas fórmulas para lactantes, en especial a base de soja, aconsejan un control específico de la cantidad del elemento y obtener información adecuada para evaluar los posibles riesgos derivados. En población adulta los aditivos alimentarios que contienen Al pueden contribuir de forma significativa a la ingesta dietética por lo que es necesario realizar estudios de toxicidad adecuados, especialmente para valorar sus efectos. El potencial neurotóxico del Al hace necesario disponer de estimaciones de la exposición dietética al mismo en nuestro país, recomendando este Comité que se deben incluir métodos que permitan identificar sus fuentes, intrínseco o adicionado (aditivos, consecuencia del procesado, migraciones a partir de envases de almacenamiento, etc.).In 2006, the FAO/WHO Joint Expert Committee on Food Additives (JECFA) took into account the effects induced by some aluminium compounds on reproduction and the development of the nervous system, and so reduced the Provisional Tolerable Weekly Intake (PTWI) of Al from 7 mg Al/kg bw/week to 1 mg Al/kg bw/week. This reduction was subsequently accepted by the European Food Safety Authority (EFSA, 2008a, 2008b), which issued a scientific opinion on the safety of consuming aluminium in the diet, in which it was estimated that a major part of the population of Europe could be exceeding the safe threshold established. Dietary exposure in adults not exposed to Al through their occupations reveals great variability from one country to another, and even within the same country. Thus, EFSA has reported that adults’ exposure through consumption of food and water ranges between 0.2-1.5 mg Al/kg bw/week for a mean weight of 60 kg and it is estimated that, among children and teenagers, dietary exposure at the 97.5 percentile is 0.7-2.3 mg Al/kg bw/week in some countries (United Kingdom and France). The available studies do not allow the identification of the specific dietary sources of Al, nor any differentiation between the multiple origins of Al including intrinsic Al, aluminium from food additives and the Al resulting from food preparation and storage processes. The aluminium content in foodstuffs analyzed in different European countries displays relatively elevated variability, even among the members of a single group. The AESAN Scientific Committee considers the new intake safety threshold set by EFSA to be adequate at 1 mg Al/kg bw/week. The Committee has highlighted the scarcity of data about Al content in food in our country. The high Al contents found in some milk formula for infants, particularly soy-based products, make it advisable to carry out a specific check of the amount of this element so as to obtain suitable information to assess the potential risks deriving from this. In an adult population, food additives containing Al may significantly contribute to dietary intake so it is necessary to conduct appropriate toxicity studies, particularly to assess their effects. The neurotoxic potential of Al means estimates must be made available on its dietary exposure in Spain and this Committee has recommended the inclusion of methods allowing its sources to be identified as intrinsic or added (food additives, a consequence of the processing, migrations from packaging materials, etc.)

Valganciclovir—Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship

Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant

Background: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. Methods: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. Results: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. Conclusions: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.This work was funded by grant Ref. no. GLD14-00279 from the GILEAD Fellowship Programme (Spain) and by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018) that is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER).S

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies