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.

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.

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-1ß, 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].

[Undergraduate student's perception of clinical simulation workshops: assessment of an instrument]. / Percepción de estudiantes de pregrado de Medicina de talleres de simulación de procedimientos médico-quirúrgicos.

BACKGROUND: Simulation is a useful training tool for undergraduate medical students. A valid instrument is needed to assess students' perception of simulation workshops. AIM: To adapt and validate an instrument to assess the undergraduate medical student's perception of simulation workshops of clinical procedures. MATERIAL AND METHODS: Delphi Methodology was used to adapt the instrument. Exploratory and confirmatory analyses were performed to determine the construct validity and Cronbach's Alpha (0 to 1) for internal consistency of the instrument. RESULTS: A Delphi panel of 10 experts adapted a seven-item questionnaire (Likert scale 1-5; ranging from 7 to 35) and four open-questions. After 3-delphi-rounds, the instrument was administered to 210 students in six simulation training programs (Paracentesis, Cardiopulmonary Resuscitation, Airway management, Sutures, Thoracentesis and Nursing Procedures). The instrument was considered unidimensional in the factorial analysis. The overall median (Q1-Q3) score was 34 ranging from 32 to 35 and the Cronbach Alpha coefficient was 0.72, indicating a good reliability. CONCLUSIONS: The perception questionnaire is a useful and reliable instrument to assess students' perceptions of clinical simulations.

Percepción de estudiantes de pregrado de Medicina de talleres de simulación de procedimientos médico-quirúrgicos / Undergraduate student's perception of clinical simulation workshops: assessment of an instrument

Background: Simulation is a useful training tool for undergraduate medical students. A valid instrument is needed to assess students' perception of simulation workshops. Aim: To adapt and validate an instrument to assess the undergraduate medical student's perception of simulation workshops of clinical procedures. Material and Methods: Delphi Methodology was used to adapt the instrument. Exploratory and confirmatory analyses were performed to determine the construct validity and Cronbach's Alpha (0 to 1) for internal consistency of the instrument. Results: A Delphi panel of 10 experts adapted a seven-item questionnaire (Likert scale 1-5; ranging from 7 to 35) and four open-questions. After 3-delphi-rounds, the instrument was administered to 210 students in six simulation training programs (Paracentesis, Cardiopulmonary Resuscitation, Airway management, Sutures, Thoracentesis and Nursing Procedures). The instrument was considered unidimensional in the factorial analysis. The overall median (Q1-Q3) score was 34 ranging from 32 to 35 and the Cronbach Alpha coefficient was 0.72, indicating a good reliability. Conclusions: The perception questionnaire is a useful and reliable instrument to assess students' perceptions of clinical simulations.

Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation.

BACKGROUND: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model. METHODS: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 μg/g/d (n = 10); (3) HFD + IGF-1 0.02 µg/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured. RESULTS: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia). CONCLUSIONS: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model.

Fragmento sérico de citoqueratina-18 como marcador no invasivo de esteatohepatitis no alcohólica en población chilena / Serum cytokeratin-18 fragment levels as noninvasive marker of nonalcoholic steatohepatitis in the chilean population

La esteatohepatitis no alcohólica (EHNA) es la forma más agresiva de hígado graso no alcohólico (HGNA) e involucra el riesgo de progresión a etapas más avanzadas de enfermedad hepática. Se requieren métodos no invasivos para identificar a pacientes con EHNA. Objetivo: Evaluar el rendimiento diagnóstico de la determinación de los niveles séricos de citoqueratina-18 como marcador no invasivo de EHNA en población chilena. Métodos: Se determinaron los niveles séricos de CK-18 en un grupo de 41 pacientes con HGNAprobado por biopsia. El diagnóstico de EHNA se basó en los criterios histológicos recomendados (presencia de balonamiento) y se calculó el puntaje de actividad del HGNA (PAH) y grado de fibrosis. Mediante correlación de Spearman se evaluó la asociación entre CK-18 y PAH. Se confeccionó una curva ROC para evaluar la capacidad de CK-18 como test diagnóstico para EHNA. Además, se evaluó el rendimiento del puntaje de fibrosis en hígado graso no alcohólico (NFS) para pesquisa de fibrosis y EHNA y se lo comparó con CK-18 por regresión lineal simple. Los datos son expresados en medianas [percentil 25-75] y evaluados con test de rangos de Wilcoxon. Resultados: La edad promedio del grupo estudiado (23% hombres) fue de 50,4 ± 11,1 años. Un 34,2% fue diagnosticado con EHNA (PAH≥5). Los niveles de CK-18 fueron mayores en los pacientes con EHNA versus los sin EHNA (183,6 UI/l [97,4-734,4] vs. 117,2 UI/l [83,8-954,8], p = 0,016). Los niveles de CK-18 fueron buenos predictores de la presencia de EHNA en la biopsia con un área bajo la curva (AUC) de 0,732 (IC95% 0,572-0,897). Un punto de corte de 130,5 UI/l de CK-18 exhibió una sensibilidad de 92,9% y una especificidad de 63%, con un VPP de 56,5% y un VPN 94,4%, y clasificó correctamente al 73,2% de los pacientes con EHNA. El NFS tuvo un buen rendimiento para diagnóstico de fibrosis avanzada (AUC 0,739, IC95% 0,56---0,91), pero limitado para identificar EHNA (AUC 0,413, IC95% 0,21-0,61). Conclusión: La determinación de CK-18 es un buen marcador no invasivo de EHNA. Si bien, NFS tiene un buen rendimiento en la identificación de pacientes con fibrosis avanzada, no fue de utilidad para diagnosticar EHNA. En pacientes con HGNA, la determinación de CK-18 y NFS es útil en la pesquisa de EHNA y fibrosis hepática respectivamente (AU)

Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH. Objective: To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population. Methods: Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt’s criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman’s rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test. Results: The mean age of the study group (23% male) was 50.4 ± 11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56---0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61). Conclusion: CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively (AU)

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis.

Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-amino-acid-defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-times/week). Also, we assessed serum levels of alanine-aminotransferase (ALT), liver histology, hepatic triglyceride content (HTC) and hepatic expression of pro-inflammatory, pro-fibrotic and inflammasome genes. Inflammasome activation was also evaluated in fat-laden HepG2 cells. Our results showed that ANDRO administration decreased HTC and attenuated hepatic inflammation and fibrosis in CDAA-fed mice. ANDRO treatment determined a strong reduction in hepatic macrophage infiltration and reduced hepatic mRNA levels of both pro-inflammatory and pro-fibrotic genes. In addition, mice treated with ANDRO showed reduced expression of inflammasome genes. Finally, ANDRO inhibited LPS-induced interleukin-1ß expression through NF-κB inhibition in fat-laden HepG2 cells and inflammasome disassembly. In conclusion, ANDRO administration reduces inflammation and fibrosis in experimental NASH. Inflammasome modulation by a NF-κB-dependent mechanism may be involved in the therapeutic effects of ANDRO.

Serum cytokeratin-18 fragment levels as noninvasive marker of nonalcoholic steatohepatitis in the chilean population. / Fragmento sérico de citoqueratina-18 como marcador no invasivo de esteatohepatitis no alcohólica en población chilena.

Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH. OBJECTIVE: To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population. METHODS: Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt's criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman's rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test. RESULTS: The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61). CONCLUSION: CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.

Diet-Induced Nonalcoholic Fatty Liver Disease Is Associated with Sarcopenia and Decreased Serum Insulin-Like Growth Factor-1.

BACKGROUND: Decreased muscle mass or sarcopenia has been associated with nonalcoholic fatty liver disease (NAFLD). However, the functional consequences of this association and its pathogenesis remain ill-defined. AIMS: To evaluate muscle mass and function in a diet-induced NAFLD mouse model and explore its association with changes in serum insulin-like growth factor-1 (IGF-1). METHODS: Weight gain, visceral fat, serum biochemical parameters, liver histology, and hepatic triglyceride content (HTC) were assessed in C57/Bl6 mice fed a westernized diet during 16 weeks. In addition, we determined muscle fiber size and strength of limb skeletal muscle, myosin heavy chain (MHC) protein levels, and IGF-1 serum levels. RESULTS: Westernized diet feeding was associated with weight gain, increased visceral fat mass (epididymal pad weight: 0.76 g ± 0.13 vs. 0.33 ± 0.27 g; p = 0.0023), hepatic steatosis (HTC: 118.2 ± 6.88 mg/g liver vs. 43.26 ± 5.63 mg/g<, p < 0.05), and necroinflammation (histological scores: 1.29 ± 0.42 vs. 4.00 ± 0.53<, p < 0.05). Also, mice fed the experimental diet had an increased proportion of low-diameter muscle fibers (0-30 µm) and a decreased proportion of high-diameter muscle fibers (60-90 µm), which correlated with decreased MHC protein levels, consistent with significant muscle atrophy. Functional studies showed that mice fed a westernized diet had reduced muscle strength and lower serum levels of IGF-1 (284.2 ± 20.04 pg/ml) compared with chow-fed mice (366.0 ± 12.42 pg/ml, p < 0.05). CONCLUSION: Experimental NAFLD is associated with sarcopenia, decreased muscle strength, and reduced IGF-1 serum levels. IGF-1 reduction may be involved in pathogenesis of NAFLD-associated sarcopenia.

Evaluation of Radiology Teachers' Performance and Identification of the "Best Teachers" in a Residency Program: Mixed Methodology and Pilot Study of the MEDUC-RX32 Questionnaire.

RATIONALE AND OBJECTIVES: Radiology teachers are well trained in their specialty; however, when working in academic institutions, faculty development and promotion through the education pathway tends to be based on their teaching knowledge and skills. The aim of this study is to assess psychometric properties of the Medicina Universidad Católica-Radiology 32 items (MEDUC-RX32), an instrument designed to evaluate the performance of postgraduate radiology teachers and to identify the best teachers. MATERIALS AND METHODS: Mixed methodology was used, including qualitative and quantitative phases. The psychometric properties of the MEDUC-RX32 survey were performed by factor analysis (validity), Cronbach alpha coefficient, and G coefficient (reliability). The residents assessed their teachers and simultaneously voted for the "best teacher," which was used as a gold standard for the receiver operating characteristic curves construction comparing their votes with the global score. RESULTS: A total of 28 residents answered 164 surveys. The global score was 6.23 ± 0.8 (scale from 1 to 7). The factor analysis showed six domains of the resident's perception: (1) tutorial teaching, feedback, and independent learning; (2) communication and teamwork; (3) learning objectives; (4) respectful behavior; (5) radiological report; and (6) teaching and care support. The tutor's strengths were related with respectful behavior and teamwork. The instrument is highly reliable with a Cronbach alpha of 0.937 and a G coefficient of 0.831 (with a minimum of 8 residents). The MEDUC-RX32 instrument has a sensitivity of 91.7% and specificity of 83.3% to identify tutors as best teachers with at least one vote with an area under the receiver operating characteristic curve of 0.931 with a cutoff of 5.94. CONCLUSIONS: The MEDC-RX32 instrument is a multidimensional, valid, and highly reliable method to evaluate radiology teachers, identifying teachers with excellence in tutorial teaching in a postgraduate radiology program.

[Development of MEDUC-PG14 survey to assess postgraduate teaching in medical specialties]. / Evaluación de docentes clínicos de Postgrado: desarrollo y propiedades psicométricas del instrumento MEDUC-PG14.

BACKGROUND: Feedback is one of the most important tools to improve teaching in medical education. AIM: To develop an instrument to assess the performance of clinical postgraduate teachers in medical specialties. MATERIAL AND METHODS: A qualitative methodology consisting in interviews and focus-groups followed by a quantitative methodology to generate consensus, was employed. After generating the instrument, psychometric tests were performed to assess the construct validity (factor analysis) and reliability (Cronbach’s alpha). RESULTS: Experts in medical education, teachers and residents of a medical school participated in interviews and focus groups. With this information, 26 categories (79 items) were proposed and reduced to 14 items (Likert scale 1-5) by an expert’s Delphi panel, generating the MEDUC-PG14 survey, which was answered by 123 residents from different programs of medical specialties. Construct validity was carried out. Factor analysis showed three domains: Teaching and evaluation, respectful behavior towards patients and health care team, and providing feedback. The global score was 4.46 ± 0.94 (89% of the maximum). One teachers’ strength, as evaluated by their residents was “respectful behavior” with 4.85 ± 0.42 (97% of the maximum). “Providing feedback” obtained 4.09 ± 1.0 points (81.8% of the maximum). MEDUC-PG14 survey had a Cronbach’s alpha coefficient of 0.947. CONCLUSIONS: MEDUC-PG14 survey is a useful and reliable guide for teacher evaluation in medical specialty programs. Also provides feedback to improve educational skills of postgraduate clinical teachers.

Evaluación de docentes clínicos de Postgrado: desarrollo y propiedades psicométricas del instrumento MEDUC-PG14 / Development of MEDUC-PG14 survey to assess postgraduate teaching in medical specialties

Background: Feedback is one of the most important tools to improve teaching in medical education. Aim: To develop an instrument to assess the performance of clinical postgraduate teachers in medical specialties. Material and Methods: A qualitative methodology consisting in interviews and focus-groups followed by a quantitative methodology to generate consensus, was employed. After generating the instrument, psychometric tests were performed to assess the construct validity (factor analysis) and reliability (Cronbach’s alpha). Results: Experts in medical education, teachers and residents of a medical school participated in interviews and focus groups. With this information, 26 categories (79 items) were proposed and reduced to 14 items (Likert scale 1-5) by an expert’s Delphi panel, generating the MEDUC-PG14 survey, which was answered by 123 residents from different programs of medical specialties. Construct validity was carried out. Factor analysis showed three domains: Teaching and evaluation, respectful behavior towards patients and health care team, and providing feedback. The global score was 4.46 ± 0.94 (89% of the maximum). One teachers’ strength, as evaluated by their residents was “respectful behavior” with 4.85 ± 0.42 (97% of the maximum). “Providing feedback” obtained 4.09 ± 1.0 points (81.8% of the maximum). MEDUC-PG14 survey had a Cronbach’s alpha coefficient of 0.947. Conclusions: MEDUC-PG14 survey is a useful and reliable guide for teacher evaluation in medical specialty programs. Also provides feedback to improve educational skills of postgraduate clinical teachers.

Measuring the educational environment in ambulatory settings / Medición del ambiente educacional en contextos ambulatorios

BACKGROUND AND OBJECTIVES: Students' perceptions of their educational environment (EE) have been studied in undergraduate and postgraduate curricula. The Ambulatory Care Learning Educational Environment Measure (ACLEEM) is an inventory that was recently developed to measure the EE in postgraduate ambulatory settings. The aim of this study was to assess the psychometric properties of the inventory. METHODS: A mixed methodology was used to develop the ACLEEM including: Grounded theory (8 focus groups); a two-round Delphi technique to identify consensus; and a pilot study. The inventory was refined to 50-items after the pilot study and it was prospectively administered to a large cohort of clerks and residents in Chile during 2010-2011. Psychometric measurements included factor analysis followed by Varimax rotation for construct validity, Cronbach's alpha coefficients for internal consistency and Generalizability theory for test reliability. RESULTS: Four-hundred and eleven students responded: 151 clerks (83.9% of the target population) and 260 residents (74% of the target population) from 31 postgraduate programs. The factor analyses showed an eight factor instrument. ACLEEM was found highly reliable with a Cronbach's alpha of 0.94 and D-study revealed a reliable outcome for residency programs with at least 15 respondents with a G coefficient of 0.831. The EE perceived by residents and clerks was positive without differences between groups: 152.52 ± 23.36 (76.26%) and 150.61 ± 24.62 (75.30%), respectively (p = 0.761). CONCLUSIONS: The 50-item ACLEEM inventory is a multidimensional and valid instrument requiring only 15 respondents for reliable RESULTS: We recommend using it to measure the EE in the ambulatory postgraduate Spanish-speaking programs

INTRODUCCIÓN Y OBJETIVOS: Las percepciones de los estudiantes sobre el ambiente educacional (AE) han sido estudiadas en programas de pregrado y posgrado. El cuestionario Ambulatory Care Learning Educational Environment Measure (ACLEEM) es un instrumento desarrollado para medir el ambiente educacional en programas de posgrado ambulatorios. El objetivo de este estudio fue evaluar las propiedades psicométricas de este instrumento. MÉTODOS: Se utilizó metodología mixta para desarrollar el instrumento ACLEEM, incluyendo: teoría fundada (8 grupos focales) y panel Delfi de 2 rondas (consenso). Se realizó un estudio piloto y luego se refinó el cuestionario a 50 ítems, que fue administrado prospectivamente en una cohorte de internos y residentes chilenos durante los años 2010-2011. Las evaluaciones psicométricas incluyeron análisis factorial seguido de rotación Varimax (validez de constructo), coeficiente alfa de Cronbach (consistencia interna) y teoría de la generalizabilidad (confiabilidad). RESULTADOS: Se obtuvieron 411 respuestas: 151 internos y 260 residentes (tasa de respuesta: 83,9% y 74%, respectivamente) correspondientes a rotaciones de internado y 31 programas de posgrado en Medicina. El análisis factorial mostró un instrumento de 8 categorías. ACLEEM presentó una alta confiabilidad (alfa de Cronbach 0,94) y un estudio de generalizabilidad que mostró resultados confiables en programas con al menos 15 encuestados (coeficiente G de 0,831). El ambiente educacional percibido por los residentes e internos fue positivo, sin diferencias entre ambos grupos: 152,52 ± 23,36 (76,26%) y 150,61 ± 24,62 (75,30%), respectivamente (p = 0,761). CONCLUSIONES: El cuestionario ACLEEM de 50 ítems es un instrumento multidimensional y válido, que requiere solo 15 encuestados para contar con resultados confiables. Recomendamos su uso para medir el ambiente educacional en programas de posgrado ambulatorios de habla hispana

[Assessment for learning: experience in an undergraduate medical theoretical course]. / Evaluación para el aprendizaje: experiencia en un curso teórico de pregrado en medicina.

BACKGROUND: Assessment for learning is a paradigm that is taking shape in the field of medical education. This approach aims to embed the assessment process within the educational and learning process. AIM: To evaluate the impact of curricular changes, from a focus of assessment of learning to one of assessment for learning, in the perception of undergraduate students of medicine and their final grades obtained in a theoretical course (TCG). MATERIAL AND METHODS: In the year 2011 lectures were reduced and intermediate assessments followed by a feedback session were introduced. The activities of each program course, surveys about student perceptions of the course and the final grades of students (assessments with multiple choice questions) were compared between the periods prior and after curricular changes (2005-2010 and 2011-2013). RESULTS: As a consequence of curricular changes, time for lectures was reduced by 19.5%, time for summative assessments was increased by 8.5%, and feedback activity, occupying 7.3% of the course time was added. There were significant improvements in student is perceptions in all areas assessed by surveys, emphasizing feedback and assessments. The overall grade assigned to the course dictated after implementing the changes increased from 6.18 to 6.59 (p < 0.001, 1-7 scale). The grades of students also improved from an average of 5.78 to 6.43 (p < 0.001, 1-7 scale). CONCLUSIONS: Assessment for learning achieved the desired educational impact without increasing the assigned curricular time. Programmatic assessment is favorably perceived by students.

[Introduction of virtual patients to clinical case portfolios for undergraduate medical students]. / Incorporación de paciente virtual en portafolio de estudiantes de medicina de pregrado.

BACKGROUND: In 2007, a Clinical-Case-Portfolio (CCP) was introduced as a new assessment instrument for fourth grade undergraduate medical students. Since then, several changes have been implemented such as reduction on the number of clinical cases, peer review and the introduction of virtual patient to the portfolio. AIM: To describe the virtual patient model incorporated to the CCP and assess the perception of this change and its effects on the performance of undergraduate students. MATERIAL AND METHODS: Virtual patients were implemented based on prototype clinical cases with specific syndromes. Students’ perceptions about CCP before and after the introduction of virtual patients were evaluated using a validated questionnaire that was answered voluntarily and anonymously. RESULTS: Overall perception of CCP significantly improved after the incorporation of virtual patients (97.1 ± 24.9 and 111.3 ± 25.7 points; 57.8 and 66.2% respectively). The same improvements were observed for the domains “Student Learning”, “Organization and Evaluation”, “Teaching Methodology” and “Integration”. In both years, students obtained high grades in CCP evaluations. However CCP grades were not significantly correlated with integrated final grades. CONCLUSIONS: The incorporation of virtual patients improved undergraduate students’ perception of CCP.

Evaluación para el aprendizaje: experiencia en un curso teórico de pregrado en medicina / Assessment for learning: experience in an undergraduate medical theoretical course

Background: Assessment for learning is a paradigm that is taking shape in the field of medical education. This approach aims to embed the assessment process within the educational and learning process. Aim: To evaluate the impact of curricular changes, from a focus of assessment of learning to one of assessment for learning, in the perception of undergraduate students of medicine and their final grades obtained in a theoretical course (TCG). Material and Methods: In the year 2011 lectures were reduced and intermediate assessments followed by a feedback session were introduced. The activities of each program course, surveys about student perceptions of the course and the final grades of students (assessments with multiple choice questions) were compared between the periods prior and after curricular changes (2005-2010 and 2011-2013). Results: As a consequence of curricular changes, time for lectures was reduced by 19.5%, time for summative assessments was increased by 8.5%, and feedback activity, occupying 7.3% of the course time was added. There were significant improvements in student is perceptions in all areas assessed by surveys, emphasizing feedback and assessments. The overall grade assigned to the course dictated after implementing the changes increased from 6.18 to 6.59 (p < 0.001, 1-7 scale). The grades of students also improved from an average of 5.78 to 6.43 (p < 0.001, 1-7 scale). Conclusions: Assessment for learning achieved the desired educational impact without increasing the assigned curricular time. Programmatic assessment is favorably perceived by students.

Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis.

BACKGROUND: Therapeutic options to treat Non-alcoholic steatohepatitis (NASH) are limited. Mineralocorticoid receptor (MR) activation could play a role in hepatic fibrogenesis and its modulation could be beneficial for NASH. AIM: To investigate whether eplerenone, a specific MR antagonist, ameliorates liver damage in experimental NASH. METHODS: C57bl6 mice were fed a choline-deficient and amino acid-defined (CDAA) diet for 22 weeks with or without eplerenone supplementation. Serum levels of aminotransferases and aldosterone were measured and hepatic steatosis, inflammation and fibrosis scored histologically. Hepatic triglyceride content (HTC) and hepatic mRNA levels of pro-inflammatory pro-fibrotic, oxidative stress-associated genes and of MR were also assessed. RESULTS: CDAA diet effectively induced fibrotic NASH, and increased the hepatic expression of pro-inflammatory, pro-fibrotic and oxidative stress-associated genes. Hepatic MR mRNA levels significantly correlated with the expression of pro-inflammatory and pro-fibrotic genes and were significantly increased in hepatic stellate cells obtained from CDAA-fed animals. Eplerenone administration was associated to a reduction in histological steatosis and attenuation of liver fibrosis development, which was associated to a significant decrease in the expression of collagen-α1, collagen type III, alpha 1 and Matrix metalloproteinase-2. CONCLUSION: The expression of MR correlates with inflammation and fibrosis development in experimental NASH. Specific MR blockade with eplerenone has hepatic anti-steatotic and anti-fibrotic effects. These data identify eplerenone as a potential novel therapy for NASH. Considering its safety and FDA-approved status, human studies are warranted.

Incorporación de paciente virtual en portafolio de estudiantes de medicina de pregrado / Introduction of virtual patients to clinical case portfolios for undergraduate medical students

Background: In 2007, a Clinical-Case-Portfolio (CCP) was introduced as a new assessment instrument for fourth grade undergraduate medical students. Since then, several changes have been implemented such as reduction on the number of clinical cases, peer review and the introduction of virtual patient to the portfolio. Aim: To describe the virtual patient model incorporated to the CCP and assess the perception of this change and its effects on the performance of undergraduate students. Material and Methods: Virtual patients were implemented based on prototype clinical cases with specific syndromes. Students’ perceptions about CCP before and after the introduction of virtual patients were evaluated using a validated questionnaire that was answered voluntarily and anonymously. Results: Overall perception of CCP significantly improved after the incorporation of virtual patients (97.1 ± 24.9 and 111.3 ± 25.7 points; 57.8 and 66.2% respectively). The same improvements were observed for the domains “Student Learning”, “Organization and Evaluation”, “Teaching Methodology” and “Integration”. In both years, students obtained high grades in CCP evaluations. However CCP grades were not significantly correlated with integrated final grades. Conclusions: The incorporation of virtual patients improved undergraduate students’ perception of CCP.

Bile acid supplementation improves established liver steatosis in obese mice independently of glucagon-like peptide-1 secretion

Bile acids or its derivatives may influence non-alcoholic fatty liver disease development through multiple mechanisms. Intestinal L-cells secrete glucagon-like peptide-1 (GLP-1) and can be activated by bile acids (BA) influencing insulin resistance and hepatic steatosis development and progression. The aim of the present study was to assess the effects of cholic acid (CA) or ursodeoxycholic acid (UDCA) administration on portal and systemic levels of GLP-1 in genetically obese mice with established hepatic steatosis. Eight-week-old ob/ob mice were fed CA or UDCA during 4 weeks. Systemic and portal GLP-1 levels were measured as well as glucose tolerance test, serum and biliary parameters, hepatic triglyceride content, liver histology, and hepatic gene expression of relevant genes related to bile secretion. Eight-week-old ob/ob mice