renovation of annals of hepatology s scientific scope towards preventing rather than treating end stage liver disease

n/

Entrenamiento y calidad de vida en la adolescencia tardía

El objetivo del estudio es determinar en ambos sexos durante la adolescencia tardía las asociaciones entre la calidad de vida relacionada con la salud (CVRS) y la práctica de deporte, la práctica de deporte competitivo, el nivel de competición, el tipo de competición, el tipo de deporte, el metabolismo y el lugar de entrenamiento. En relación a la metodología, evaluamos en 2.831 adolescentes (1.315 chicas) de 16-19 años la CVRS con el cuestionario KIDSCREEN-52. 413 sujetos eran inactivos, 1.008 hacían deporte no competitivo, 649 competían a nivel local/regional y 761 a nivel nacional/internacional en modalidades incluidas en el programa de los JJOO de verano. Categorizamos a los deportistas que compiten según el tipo de competición (individual, colectivo), tipo de deporte (continuo, técnico, equipo, gimnástico, combate, potencia, raqueta), metabolismo predominante (aláctico, láctico, aeróbico, mixto) y lugar de entrenamiento (aire libre, sala). Respecto a los resultados, las chicas mostraron peor CVRS que los chicos. Los adolescentes inactivos mostraron peor CVRS que los que realizaban deporte no competitivo. Los adolescentes que realizaban deporte no competitivo mostraron peor CVRS que los que realizaban deporte competitivo. Los adolescentes que competían a nivel nacional/internacional tuvieron mejor CVRS que los que competían a nivel local/regional. El tipo de competición, el tipo de deporte, el metabolismo predominante y el lugar de entrenamiento no se asoció con la CVRS.Finalmente podemos concluir que en ambos sexos, durante la adolescencia tardía, la práctica de deporte, especialmente a un elevado nivel de competición se asocia con una mejor CVRS, sin influencia del tipo de competición, tipo de deporte, metabolismo predominante y lugar de entrenamiento.<br /

Mega mercado municipal en Sullana

En el presente trabajo se expone el planificación y principio del proyecto “Mega Mercado Municipal de Sullana”, ubicado Sullana, Piura. Este proyecto parte con el estudio y análisis de la problemática de la zona, la cual se basa principalmente, en la necesidad de los comerciantes de tener un lugar de calidad para poder ofrecer sus productos a los consumidores. Para el desarrollo del proyecto se realizo varias visitas de campo para analizar los posibles usuarios y/o beneficiarios para saber sus necesidades y funciones a realizar en el proyecto, ademas de zonas y sub zonas a desarrollar en el proyecto; posteriormente procesaremos la información obtenida mediante cuadros y estadisticas y datos reales sobre los números de puestos comerciales formales y el número de comerciantes informales de cada zona y subzona a la que pertenecen cada uno, tratando de cumplir con la demanda requerida y ofertar mas puestos requeridos para un futuro crecimiento de número de comerciantes en el mercado. Tambien realizamos un analis de casos analogos de mercados nacionales e internacional los cuales funcionan exitosamente, para tener un conocimiento previo a diseñar nuestro proyecto y asi entender el funcionamiento del mercado y sus respectivas zonas. Ya con los datos obtenidos en la investigación pasamos a realizar nuestra propuesta de Mega Mercado Municipal de Sullana, basandonos en las normativas del Reglamento Nacional de Edificaciones y los parametros Urbanisticos de la ciudad, para asi satisfacer las necesidades demandadas por los usuarios para poder brindar mejor la compra y venta de productos y a la vez la calidad del servicio mejorando la economía del distrito y provincia. Por último, el proyecto arquitectonico se ha realizado en paralelo con el análisis estructural, instalaciones electricas, instalaciones sanitarias, condiciones de seguridad normadas e instalaciones mecánicas.In the present work the planning and principle of the project “Mega Mercado Municipal de Sullana”, located in Sullana, Piura, are exposed. This project starts with the study and analysis of the problems of the area, which is mainly based on the need for merchants to have a quality place to offer their products to consumers. For the development of the project, several field visits were made to analyze the possible users and / or beneficiaries to know their needs and functions to be carried out in the project, in addition to the zones and sub-zones to be developed in the project; Subsequently, we will process the information obtained through tables and statistics and real data on the numbers of formal business positions and the number of informal merchants in each zone and sub-zone to which each one belongs, trying to meet the required demand and offer more positions required to a future growth in the number of merchants in the market. We also carry out an analysis of analog cases of national and international markets which work successfully, to have prior knowledge to design our project and thus understand the operation of the market and its respective areas. With the data obtained in the research, we now carry out our proposal for the Sullana Municipal Mega Market, based on the regulations of the National Building Regulations and the urban parameters of the city, in order to satisfy the needs demanded by users in order to better provide the purchase and sale of products and at the same time the quality of the service improving the economy of the district and province. Finally, the architectural project has been carried out in parallel with the structural analysis, electrical installations, sanitary installations, regulated security conditions and mechanical installations.Tesi

Serum biomarkers for the prediction of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Major etiologies of HCC relate to chronic viral infections as well as metabolic conditions. The survival rate of people with HCC is very low and has been attributed to late diagnosis with limited treatment options. Combining ultrasound and the biomarker alpha-fetoprotein (AFP) is currently one of the most widely used screening combinations for HCC. However, the clinical utility of AFP is controversial, and the frequency and operator-dependence of ultrasound lead to a variable degree of sensitivity and specificity across the globe. In this review, we summarize recent developments in the search for non-invasive serum biomarkers for early detection of HCC to improve prognosis and outcome for patients. We focus on tumor-associated protein markers, immune mediators (cytokines and chemokines), and micro-RNAs in serum or circulating extracellular vesicles and examine their potential for clinical application.Fil: Debes, José D.. Erasmus MC Rotterdam; Países Bajos. University of Minnesota; Estados UnidosFil: Romagnoli, Pablo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Prieto, Jhon. Centro de Enfermedades Hepáticas y Digestivas; ColombiaFil: Arrese, Marco. Pontificia Universidad Católica de Chile; ChileFil: Mattos, Angelo Z.. Universidade Federal de Ciencias Da Saúde de Porto Alegre; BrasilFil: Boonstra, André. Erasmus MC Rotterdam; Países Bajo

Extracellular Vesicles in NAFLD/ALD:From Pathobiology to Therapy

In recent years, knowledge on the biology and pathobiology of extracellular vesicles (EVs) has exploded. EVs are submicron membrane-bound structures secreted from different cell types containing a wide variety of bioactive molecules (e.g., proteins, lipids, and nucleic acids (coding and non-coding RNA) and mitochondrial DNA). EVs have important functions in cell-to-cell communication and are found in a wide variety of tissues and body fluids. Better delineation of EV structures and advances in the isolation and characterization of their cargo have allowed the diagnostic and therapeutic implications of these particles to be explored. In the field of liver diseases, EVs are emerging as key players in the pathogenesis of both nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD), the most prevalent liver diseases worldwide, and their complications, including development of hepatocellular carcinoma. In these diseases, stressed/damaged hepatocytes release large quantities of EVs that contribute to the occurrence of inflammation, fibrogenesis, and angiogenesis, which are key pathobiological processes in liver disease progression. Moreover, the specific molecular signatures of released EVs in biofluids have allowed EVs to be considered as promising candidates to serve as disease biomarkers. Additionally, different experimental studies have shown that EVs may have potential for therapeutic use as a liver-specific delivery method of different agents, taking advantage of their hepatocellular uptake through interactions with specific receptors. In this review, we focused on the most recent findings concerning the role of EVs as new structures mediating autocrine and paracrine intercellular communication in both ALD and NAFLD, as well as their potential use as biomarkers of disease severity and progression. Emerging therapeutic applications of EVs in these liver diseases were also examined, along with the potential for successful transition from bench to clinic

The use of sports psychology consultants in elite sports teams

This study investigates the use of psychology services in teams of the top division Spanish leagues of handball, basketball, volleyball, indoor soccer, soccer and field hockey. Personal interviews were conducted to determine the composition of the multidisciplinary teams. The response rate was 81.8% (77 of 94). Though most teams have different professionals employed on a full-time basis, only 15.6% of these teams have a sport psychologist. Moreover, only three teams have a full-time sports psychologist. These results indicate that, compared to other professional services, managers and/or coaches do not perceive the need for psychological services. We discarded the hypothesis that most of the teams do not hire psychologists due to financial reasons. Sport psychology associations should reinforce the importance of the psychologist to enhance sports performance

Chemical hypoxia induces pro-inflammatory signals in fat-laden hepatocytes and contributes to cellular crosstalk with Kupffer cells through extracellular vesicles

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated to intermittent hypoxia (IH) and is an aggravating factor of non-alcoholic fatty liver disease (NAFLD). We investigated the effects of hypoxia in both in vitro and in vivo models of NAFLD. METHODS: Primary rat hepatocytes treated with free fatty acids (FFA) were subjected to chemically induced hypoxia (CH) using the hypoxia-inducible factor-1 alpha (HIF-1α) stabilizer cobalt chloride (CoCl2). Triglyceride (TG) content, mitochondrial superoxide production, cell death rates, cytokine and inflammasome components gene expression and protein levels of cleaved caspase-1 were assessed. Also, Kupffer cells (KC) were treated with conditioned medium (CM) and extracellular vehicles (EVs) from hypoxic fat-laden hepatic cells. The choline deficient L-amino acid defined (CDAA)-feeding model used to assess the effects of IH on experimental NAFLD in vivo. RESULTS: Hypoxia induced HIF-1α in cells and animals. Hepatocytes exposed to FFA and CoCl2 exhibited increased TG content and higher cell death rates as well as increased mitochondrial superoxide production and mRNA levels of pro-inflammatory cytokines and of inflammasome-components interleukin-1β, NLRP3 and ASC. Protein levels of cleaved caspase-1 increased in CH-exposed hepatocytes. CM and EVs from hypoxic fat-laden hepatic cells evoked a pro-inflammatory phenotype in KC. Livers from CDAA-fed mice exposed to IH exhibited increased mRNA levels of pro-inflammatory and inflammasome genes and increased levels of cleaved caspase-1. CONCLUSION: Hypoxia promotes inflammatory signals including inflammasome/caspase-1 activation in fat-laden hepatocytes and contributes to cellular crosstalk with KC by release of EVs. These mechanisms may underlie the aggravating effect of OSAS on NAFLD. [Abstract word count: 257]

Hepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles

Liver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one-directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications. Therefore, the aim of the present study was to investigate the role of HSCs on the inflammatory phenotype of KCs. Primary rat HSCs and KCs were isolated from male Wistar rats. HSCs-derived conditioned medium (CM) was harvested from different time intervals (Day 0−2: CM-D2 and Day 5−7: CM-D7) during the activation of HSCs. Extracellular vesicles (EVs) were isolated from CM by ultracentrifugation and evaluated by nanoparticle tracking analysis and western blot analysis. M1 and M2 markers of inflammation were measured by quantitative PCR and macrophage function by assessing phagocytic capacity. CM-D2 significantly induced the inflammatory phenotype in KCs, but not CM-D7. Neither CM-D2 nor CM-D7 affected the phagocytosis of KCs. Importantly, the proinflammatory effect of HSCs-derived CM is mediated via EVs released from HSCs since EVs isolated from CM mimicked the effect of CM, whereas EV-depleted CM lost its ability to induce a proinflammatory phenotype in KCs. In addition, when the activation of HSCs was inhibited, HSCs produced less EVs. Furthermore, the proinflammatory effects of CM and EVs are related to activating Toll-like receptor 4 (TLR4) in KCs. In conclusion, HSCs at an early stage of activation induce a proinflammatory phenotype in KCs via the release of EVs. This effect is absent in CM derived from HSCs at a later stage of activation and is dependent on the activation of TLR4 signaling pathway.</p

Extracellular vesicles derived from fat-laden hepatocytes undergoing chemical hypoxia promote a pro-fibrotic phenotype in hepatic stellate cells

Background: The transition from steatosis to non-alcoholic steatohepatitis (NASH) is a key issue in non-alcoholic fatty liver disease (NAFLD). Observations in patients with obstructive sleep apnea syndrome (OSAS) suggest that hypoxia contributes to progression to NASH and liver fibrosis, and the release of extracellular vesicles (EVs) by injured hepatocytes has been implicated in NAFLD progression. Aim: To evaluate the effects of hypoxia on hepatic pro-fibrotic response and EV release in experimental NAFLD and to assess cellular crosstalk between hepatocytes and human hepatic stellate cells (LX-2). Methods: HepG2 cells were treated with fatty acids and subjected to chemically induced hypoxia using the hypoxia-inducible factor 1 alpha (HIF-1α) stabilizer cobalt chloride (CoCl2). Lipid droplets, oxidative stress, apoptosis and pro-inflammatory and pro-fibrotic-associated genes were assessed. EVs were isolated by ultracentrifugation. LX-2 cells were treated with EVs from hepatocytes. The CDAA-fed mouse model was used to assess the effects of intermittent hypoxia (IH) in experimental NASH. Results: Chemical hypoxia increased steatosis, oxidative stress, apoptosis and pro-inflammatory and pro-fibrotic gene expressions in fat-laden HepG2 cells. Chemical hypoxia also increased the release of EVs from HepG2 cells. Treatment of LX2 cells with EVs from fat-laden HepG2 cells undergoing chemical hypoxia increased expression pro-fibrotic markers. CDAA-fed animals exposed to IH exhibited increased portal inflammation and fibrosis that correlated with an increase in circulating EVs. Conclusion: Chemical hypoxia promotes hepatocellular damage and pro-inflammatory and pro-fibrotic signaling in steatotic hepatocytes both in vitro and in vivo. EVs from fat-laden hepatocytes undergoing chemical hypoxia evoke pro-fibrotic responses in LX-2 cells

Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease

Hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567 genotypes and the hepatic transcriptome. The A-INS allele protected against NAFLD [odds ratio (OR) per adenine allele = 0.667; 95% CI, 0.486−0.916; P = 0.012]; this effect was nonsignificant when logistic regression analysis included BMI. The A-INS allele protected against nonalcoholic steatohepatitis (NASH) (OR = 0.612; 95% CI, 0.388−0.964; P = 0.033), ballooning degeneration (OR = 0.474; 95% CI, 0.267−0.842; P = 0.01), lobular inflammation (OR = 0.475; 95% CI, 0.275−0.821; P = 0.007), and fibrosis (OR = 0.590; 95% CI, 0.361−0.965; P = 0.035). In patients carrying A-INS, HSD17B13 levels decreased proportionally to allele dosage. Whole-transcriptome genotype profiling showed overrepresented immune response-related pathways. Thus, the rs72613567 A-INS allele reduces the risk of NASH and progressive liver damage and may become a therapeutic target.Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Garaycoechea, Martin. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Arrese, Marco. Pontificia Universidad Católica de Chile; ChileFil: San Martino, Julio. Hospital Diego Thompson; ArgentinaFil: Gazzi, Carla. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Casta&ntildeo, Gustavo O. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin