Evaluación de docentes y jefes de programas de residencia en posgrado

La formación en docencia es central en la educación médica. La percepción de los estudiantes respecto a las habilidades de sus docentes es muchas veces desconocida. La retroalimentación desde los estudiantes hacia los docentes permite la mejoría continua. Objetivo: Evaluar la percepción que tienen los médicos residentes de programas de especialidad y subespecialidad respecto a las habilidades y actitudes de sus docentes de la Pontificia Universidad Católica de Chile.MétodosSe realizó una encuesta electrónica a 415 residentes de especialidad y subespecialidad. La encuesta incluyó preguntas de evaluación a sus docentes en general y, en particular, al Jefe de Programa con una escala Likert de 1 a 5, donde 1 significaba no o nunca y 5 sí o siempre.ResultadosAl ser consultados los residentes si han evaluado a sus docentes un 38.3% nunca o pocas veces lo hizo y un 37.6% de las veces lo realizó siempre o casi siempre. Al evaluar a los docentes en general, la mayoría obtuvo un puntaje mayor o igual a 4 (casi siempre o siempre) en los ítems evaluados: motivación y dedicación (79.4%), buenas destrezas docentes (71.5%), dominio de los temas (96.2%), respuesta adecuada durante los turnos (80%) y adecuadas habilidades de comunicación (70.7%). Al preguntar solo por los Jefes de Programas se repite la tendencia, siendo el ítem mejor evaluado las habilidades cognitivas de conocimiento (dominio de los temas que enseña) obteniendo un puntaje mayor o igual a 4 en el 96.1% de los encuestados y el ítem peor evaluado fueron las habilidades de comunicación obteniendo un 77.35% de los encuestados un puntaje mayor o igual a 4 (casi siempre o siempre), en un 14.7% de los encuestados obtuvo un puntaje de 3 (correspondiente a la respuesta: 50% de las veces) y un 7.95% de los encuestados contestó 1 o 2 (nunca o pocas veces).ConclusiónLa evaluación de los docentes y de los jefes de programa de residencia en Posgrado permite el perfeccionamiento continuo y orienta hacia qué áreas enfocar la formación de los formadores, pudiendo desarrollar talleres con objetivos ajustados a las necesidades individuales por programa, en este caso, se debe trabajar en perfeccionar las habilidades de comunicación de los docentes y Jefes de Programa

Characterization of extracellular vesicles and synthetic nanoparticles with four orthogonal single-particle analysis platforms

Ingreso parcial de los coautores.We compared four orthogonal technologies for sizing, counting, and phenotyping of extracellular vesicles (EVs) and synthetic particles. The platforms were: singleparticle interferometric reflectance imaging sensing (SP-IRIS) with fluorescence, nanoparticle tracking analysis (NTA) with fluorescence, microfluidic resistive pulse sensing (MRPS), and nanoflow cytometry measurement (NFCM). EVs from the human T lymphocyte line H9 (high CD81, low CD63) and the promonocytic line U937 (low CD81, high CD63) were separated from culture conditioned medium (CCM) by differential ultracentrifugation (dUC) or a combination of ultrafiltration (UF) and size exclusion chromatography (SEC) and characterized by transmission electron microscopy (TEM) and Western blot (WB). Mixtures of synthetic particles.(silica and polystyrene spheres) with known sizes and/or concentrations were also tested.MRPS andNFCMreturned similar particle counts,whileNTAdetected counts approximately one order of magnitude lower for EVs, but not for synthetic particles. SP-IRIS events could not be used to estimate particle concentrations. For sizing, SPIRIS, MRPS, and NFCM returned similar size profiles, with smaller sizes predominating (per power law distribution), but with sensitivity typically dropping off below diameters of 60 nm. NTA detected a population of particles with a mode diameter greater than 100 nm. Additionally, SP-IRIS, MRPS, and NFCM were able to identify at least three of four distinct size populations in a mixture of silica or polystyrene nanoparticles. Finally, for tetraspanin phenotyping, the SP-IRIS platform in fluorescencemode was able to detect at least twomarkers on the same particle, while NFCM detected either CD81 or CD63. Based on the results of this study, we can draw conclusions about existing single-particle analysis capabilities that may be useful for EV biomarker development and mechanistic studies

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

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]

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

Mineralocorticoid Receptor Modulation by Dietary Sodium Influences NAFLD Development in Mice

Introduction and Objectives Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD. Materials and Methods C57BL/6J mice were fed either a high-fat-diet (HFD) or a choline/methionine deficient (MCD) diet with different sodium concentrations. Hepatic concentration of lipid species, serum aldosterone levels, expression of MR, proinflammatory and profibrotic markers and liver histology were assessed. Results Mice fed with High-Na+/HFD showed a lower MR expression in liver (p = 0.01) and less steatosis on histology (p = 0.04). Consistently, animals from this group exhibited lower levels of serum aldosterone (p = 0.028) and lower hepatic triglyceride content (p = 0.008). This associated to a reduced expression of lipogenic genes, significant changes in lipid subspecies, lower HOMA-IR (p < 0.05), and lower expression of pro-inflammatory and profibrotic markers compared to those mice fed a Low-Na+/HFD. Additionally, mice fed a High-Na+/HFD showed higher expression of salt-inducible kinase (SIK)-1 and lower expression of serum-and-glucocorticoid-inducible kinase (SGK)-1. Similar results were observed with the MCD diet model. Conclusion We identified in two experimental models of NAFLD that High-Na+ diet content is associated to lower serum aldosterone levels and hepatic MR downregulation, associated to decreased steatosis and reduced de novo hepatic lipogenesis, proinflammatory and profibrotic markers. Decreased activation of hepatic MR seems to generate beneficial downstream inhibition of lipogenesis in experimental NAFLD.This work was funded, in part, by grants from the Chilean Government [FONDECYT #1150327 and #1191145 to M.A.; #1200227 to JPA; #1190419 to R.B and #1191183 to F.B.; #1211879 to D.C.) and the Comisión Nacional de Investigación Científica y Tecnológica (CONICYT, AFB170005, CARE Chile UC)]. MA is part of the European- Latin American ESCALON consortium funded by the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 825510. Funding from Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT971-16 to P.A.), MCIU/AEI/FEDER, UE (RTI2018-095134-B-100 to P.A) is also acknowledged

A multisociety Delphi consensus statement on new fatty liver disease nomenclature

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.Fil: Rinella, Mary E.. University of Chicago; Estados UnidosFil: Lazarus, Jeffrey V.. City University of New York; Estados Unidos. Universidad de Barcelona; EspañaFil: Ratziu, Vlad. Sorbonne University; FranciaFil: Francque, Sven M.. Universiteit Antwerp; BélgicaFil: Sanyal, Arun J.. Virginia Commonwealth University; Estados UnidosFil: Kanwal, Fasiha. Baylor College of Medicine; Estados UnidosFil: Romero, Diana. City University of New York; Estados UnidosFil: Abdelmalek, Manal F.. Mayo Clinic; Estados UnidosFil: Anstee, Quentin M.. University of Newcastle; Reino Unido. The Newcastle Upon Tyne Hospitals Nhs Foundation Trust; Reino UnidoFil: Arab, Juan Pablo. Western University; Canadá. Pontificia Universidad Católica de Chile; ChileFil: Arrese, Marco. Escuela de Medicina; Chile. Latin American Association For The Study Of The Liver (aleh) Santiago; ChileFil: Bataller, Ramon. Institut d'Investigacions Biomediques August Pi i Sunyer; EspañaFil: Beuers, Ulrich. University of Amsterdam; Países BajosFil: Boursier, Jerome. Angers University; Estados UnidosFil: Bugianesi, Elisabetta. Università di Torino; ItaliaFil: Byrne, Christopher D.. University of Southampton; Reino UnidoFil: Castro Narro, Graciela E.. Instituto Nacional de la Nutrición Salvador Zubiran; México. Latin American Association for the Study of the Liver; Chile. Fundacion Clinica Medica Sur; MéxicoFil: Chowdhury, Abhijit. Indian Institute Of Liver And Digestive Sciences; India. Universidade Nova de Lisboa; PortugalFil: Cortez Pinto, Helena. Universidade Nova de Lisboa; PortugalFil: Cryer, Donna R.. University of Florida; Estados UnidosFil: Cusi, Kenneth. University of Florida; Estados UnidosFil: El Kassas, Mohamed. Washington University School of Medicine; Estados UnidosFil: Klein, Samuel. University of Washington; Estados UnidosFil: Sookoian, Silvia Cristina. Universidad Maimónides; Argentina. University of Cape Town; Sudáfrica. Pontificia Universidad Católica de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yilmaz, Yusuf. Inova Health System; Estados UnidosFil: Younossi, Zobair. University Of Birmingham; . Universidad de Barcelona; EspañaFil: Hobbs, Ansley. City University of New York; Estados UnidosFil: Villota Rivas, Marcela. University Of Birmingham;Fil: Newsome, Philip N.. University Of Birmingham

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a threeday in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a supermajority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat.Fil: Lazarus, Jeffrey V.. City University of New York; Estados Unidos. Universidad de Barcelona; EspañaFil: Mark, Henry E.. European Association for the Study of the Liver; SuizaFil: Allen, Alina M.. Mayo Clinic; Estados UnidosFil: Arab, Juan Pablo. Pontificia Universidad Católica de Chile; Chile. Western University; CanadáFil: Carrieri, Patrizia. Inserm; Francia. Sciences Economiques & Sociales de la Santé & Traitement de l’Information Médicale; FranciaFil: Noureddin, Mazen. Houston Methodist Hospital; Estados UnidosFil: Alazawi, William. Queen Mary University of London; Estados UnidosFil: Alkhouri, Naim. Arizona Liver Health; Estados UnidosFil: Alqahtani, Saleh A.. King Faisal Specialist Hospital And Research Centre; Arabia SauditaFil: Arrese, Marco. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Bataller, Ramon. Universidad de Barcelona; EspañaFil: Berg, Thomas. Universitat Leipzig; AlemaniaFil: Brennan, Paul N.. University of Dundee; Reino UnidoFil: Burra, Patrizia. Università di Padova; ItaliaFil: Castro Narro, Graciela E.. Instituto Nacional de la Nutrición Salvador Zubiran; México. Fundacion Clinica Medica Sur; México. Asociación Latinoamericana Para El Estudio del Hígado; ChileFil: Cortez Pinto, Helena. Universidade Nova de Lisboa; PortugalFil: Cusi, Kenneth. University of Florida; Estados UnidosFil: Dedes, Nikos. Greek Patients Association; GreciaFil: Duseja, Ajay. Postgraduate Institute of Medical Education and Research; IndiaFil: Francque, Sven M.. Universiteit Antwerp; BélgicaFil: Hagström, Hannes. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Huang, Terry T. K.. City University of New York; Estados UnidosFil: Wajcman, Dana Ivancovsky. Universidad de Barcelona; EspañaFil: Valenti, Luca. Università degli Studi di Milano; ItaliaFil: Zelber-Sagi, Shira. University Of Haifa; Israel. Universitat Tel Aviv; IsraelFil: Schattenberg, Jörn M.. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Wong, Vincent Wai-Sun. Chinese University Of Hong Kong; Hong KongFil: Younossi, Zobair M.. Universiteit Antwerp; BélgicaFil: Zheng, Kenneth I.. Universiteit Antwerp; BélgicaFil: 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; Argentina. Universidad Abierta Interamericana; Argentin

A global research priority agenda to advance public health responses to fatty liver disease

BACKGROUND & AIMS: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. METHODS: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. RESULTS: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had 90% combined agreement. CONCLUSIONS: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. IMPACT AND IMPLICATIONS: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat