RESUMEN
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.
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Enfermedad del Hígado Graso no Alcohólico/metabolismo , Receptores de Mineralocorticoides/metabolismo , Sodio en la Dieta/administración & dosificación , Aldosterona/sangre , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Triglicéridos/metabolismoRESUMEN
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].
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Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Hipoxia/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Apnea Obstructiva del Sueño/genética , Animales , Caspasa 1/genética , Deficiencia de Colina/genética , Deficiencia de Colina/metabolismo , Deficiencia de Colina/patología , Cobalto/toxicidad , Modelos Animales de Enfermedad , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patología , Ácidos Grasos no Esterificados/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Hipoxia/inducido químicamente , Hipoxia/metabolismo , Hipoxia/patología , Inflamasomas/genética , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/genética , Macrófagos del Hígado/metabolismo , Macrófagos del Hígado/patología , Ratones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Ratas , Apnea Obstructiva del Sueño/etiología , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/patología , Triglicéridos/genéticaRESUMEN
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.
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Competencia Clínica/normas , Educación de Pregrado en Medicina/métodos , Percepción , Entrenamiento Simulado/métodos , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios/normas , Técnica Delphi , Análisis Factorial , Retroalimentación Formativa , Humanos , Estándares de Referencia , Reproducibilidad de los Resultados , Procedimientos Quirúrgicos Operativos/educación , Procedimientos Quirúrgicos Operativos/psicologíaRESUMEN
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.
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Humanos , Percepción , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios/normas , Competencia Clínica/normas , Educación de Pregrado en Medicina/métodos , Entrenamiento Simulado/métodos , Estándares de Referencia , Procedimientos Quirúrgicos Operativos/educación , Procedimientos Quirúrgicos Operativos/psicología , Reproducibilidad de los Resultados , Análisis Factorial , Técnica Delphi , Retroalimentación FormativaRESUMEN
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.
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Suplementos Dietéticos , Hormona del Crecimiento/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/terapia , Adiponectina/sangre , Alanina Transaminasa/sangre , Animales , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Hormona del Crecimiento/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Leptina/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Contracción Muscular , Fuerza Muscular , Enfermedad del Hígado Graso no Alcohólico/patología , Triglicéridos/metabolismoRESUMEN
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.
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Antiinflamatorios no Esteroideos/administración & dosificación , Diterpenos/administración & dosificación , Inflamasomas/metabolismo , Inflamación/prevención & control , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Animales , Células Cultivadas , Fibrosis/prevención & control , Inflamación/complicaciones , Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Ratas WistarRESUMEN
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.
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Queratina-18/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Adulto , Biomarcadores/sangre , Biopsia , Chile/epidemiología , Femenino , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Fragmentos de Péptidos/sangre , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
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.
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Dieta Occidental , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hígado/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Sarcopenia/metabolismo , Animales , Modelos Animales de Enfermedad , Grasa Intraabdominal , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Fibras Musculares Esqueléticas/patología , Fuerza Muscular/fisiología , Músculo Esquelético/patología , Cadenas Pesadas de Miosina/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Sarcopenia/patología , Sarcopenia/fisiopatología , Triglicéridos/metabolismo , Aumento de PesoRESUMEN
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.
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Internado y Residencia , Competencia Profesional , Radiología/educación , Encuestas y Cuestionarios , Enseñanza , Adulto , Comunicación , Femenino , Retroalimentación Formativa , Humanos , Masculino , Proyectos Piloto , Evaluación de Programas y Proyectos de Salud , Psicometría , Reproducibilidad de los ResultadosRESUMEN
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 (Cronbachs 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 experts 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 Cronbachs 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.
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Educación Médica/normas , Docentes Médicos/normas , Proyectos de Investigación/normas , Grupos Focales , Humanos , Entrevistas como Asunto , Psicometría , Investigación Cualitativa , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Enseñanza/métodos , Enseñanza/normasRESUMEN
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 (Cronbachs 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 experts 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 Cronbachs 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.
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Humanos , Educación Médica/normas , Docentes Médicos/normas , Proyectos de Investigación/normas , Grupos Focales , Entrevistas como Asunto , Psicometría , Investigación Cualitativa , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Enseñanza/métodos , Enseñanza/normasRESUMEN
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.
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Curriculum , Educación de Pregrado en Medicina/métodos , Gastroenterología/educación , Aprendizaje , Evaluación Educacional , Humanos , Conocimiento Psicológico de los Resultados , Percepción , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
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.
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Documentación , Educación de Pregrado en Medicina/métodos , Evaluación Educacional/métodos , Materiales de Enseñanza , Competencia Clínica , Humanos , Percepción , Encuestas y Cuestionarios , Adulto JovenRESUMEN
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.
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Humanos , Curriculum , Educación de Pregrado en Medicina/métodos , Gastroenterología/educación , Aprendizaje , Evaluación Educacional , Conocimiento Psicológico de los Resultados , Percepción , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
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.
Asunto(s)
Cirrosis Hepática/patología , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Estrés Oxidativo/genética , Receptores de Mineralocorticoides/metabolismo , Espironolactona/análogos & derivados , Animales , Biomarcadores/análisis , Modelos Animales de Enfermedad , Eplerenona , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Mineralocorticoides/genética , Espironolactona/administración & dosificaciónRESUMEN
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.
Asunto(s)
Animales , Ratones , Apoptosis , Proteína Axina/metabolismo , Activación Enzimática , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Factor Inductor de la Apoptosis/genética , Factor Inductor de la Apoptosis/metabolismo , Aurora Quinasas , Línea Celular , Membrana Celular/metabolismo , Membrana Celular/fisiología , Mitocondrias/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Interferencia de ARN , Imagen de Lapso de TiempoRESUMEN
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 exhibited marked obesity, hyperinsulinemia, and fasting hyperglycemia. Administration of both CA and UDCA was associated to decreased hepatic triglyceride content and complete reversion of histological steatosis. BA-fed animals did not exhibit significant differences in glucose tolerance. In addition, neither CA nor UDCA administration significantly influenced portal or systemic GLP-1 levels. CA and UDCA strongly ameliorated established fatty liver in ob/ob mice independently of the GLP-1 incretin pathway. Thus, the anti-steatotic action of these bile acids is likely related to direct hepatic effects.
Asunto(s)
Ácidos y Sales Biliares/administración & dosificación , Péptido 1 Similar al Glucagón/sangre , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP , Transportadoras de Casetes de Unión a ATP/genética , Animales , Colesterol 7-alfa-Hidroxilasa/genética , Ácido Cólico/administración & dosificación , Expresión Génica/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Incretinas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/patología , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Receptores Citoplasmáticos y Nucleares/genética , Simportadores/genética , Triglicéridos/metabolismo , Ácido Ursodesoxicólico/administración & dosificaciónRESUMEN
BACKGROUND: Determination of Alanine aminotransferase serum levels ([ALT]s) is a sensitive ana reliable test for liver diseases. AIM: To report the prevalence of abnormal [ALT]s in Chilean population and to identify associated variables. METHODS: We analyzed data from a random sub-sample of 2,794 adults surveyed during the second Chilean National Health Survey. Abnormal [ALT]s were defined by using three different cut-off values (COV), two fixed COV (COV1: > 30 IU/L in men and > 19 IU/L in women and COV2 pre-defined by the performing laboratory) and a COV adjusted by age, weight and sex (COV3 > 31 IU/L for women and > 44 IU/L and men > 42 IU/L and > 66 IU/L with a BMI > 23). Logistic regression analysis was performed to determine risk factors for elevated [ALT]s. RESULTS: Mean [ALT]s values were 30.14 I U/L in men and 22.03 IU/L in women. The observed prevalence of abnormal [ALT]s defined by different COV were 38%, 11.5%, and 8.1% for COV1, COV2 and COV3 respectively. Variables independently associated to abnormal [ALT]s in a multivariate analysis were the following: serum gamma-glutamyl-transpeptidase (OR: 1.055 [95% CI 1.033-1.078]) and body mass index (OR:1.13 [95% CI 1.09-1.17]). Variables inversely associated with abnormal [ALT]s (COV1) were mole gender (OR-.0.976 [95% CI 0.96-0.99) and HDL-cholesterol (OR:0979 [95% CI 0.96-0.99]). CONCLUSIONS: Independently of the COV used, Chilean population exhibits a high prevalence of abnormal [ALT]s which may reflect a significant burden of liver disease. Non-alcoholic fatty liver disease could be a major contributor to elevated [ALT]s considering the association of abnormal [ALT]s and metabolic variables.
Asunto(s)
Alanina Transaminasa/sangre , Adulto , Biomarcadores/sangre , Chile , Femenino , Encuestas Epidemiológicas , Humanos , Hepatopatías/diagnóstico , Hepatopatías/enzimología , Masculino , Prevalencia , Valores de Referencia , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Training of postgraduate medical specialty program managers (PMSPM) is essential for the proper development of their programs. Aim: To identify the main training needs of PMSPM at a medical school. Material and Methods: A mixed-methodology approach was implemented including focus group/interviews and the administration of the Program Managers Training Needs Assessment Questionnaire (PROMANAQ) developed by an expert panel with 59 items (with two sections: relevance/performance-self-perception). Higher priority was assigned to items with high relevance and low performance. Results: Forty five PMSPM completed the PROMANAQ (81.8% response rate). Both sections of PROMANAQ were highly reliable (Cronbach alpha of 0.95/0.97 for relevance/performance-self-perception, respectively). The items with higher priority value were evaluation of clinical educators, evaluation of teaching programs and accreditation of programs. Ten PMSPM were included in the focus group (18.2% of the universe). The findings of the qualitative component were concordant with the areas explored in the questionnaire. Conclusions: The PROMANAQ is valid and reliable to identify the training needs of PMSPM. The views of PMSPM must be taken into account for faculty development planning.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Educación Continua/organización & administración , Docentes , Capacitación en Servicio/métodos , Facultades de Medicina/estadística & datos numéricos , Chile , Evaluación de Necesidades , UniversidadesRESUMEN
Background: Determination of Alanine aminotransferase serum levels ([ALT]s) is a sensitive ana reliable test for liver diseases. Aim: To report the prevalence of abnormal [ALT]s in Chilean population and to identify associated variables. Methods: We analyzed data from a random sub-sample of 2,794 adults surveyed during the second Chilean National Health Survey. Abnormal [ALT]s were defined by using three different cut-off values (COV), two fixed COV (COV1: > 30 IU/L in men and > 19 IU/L in women and COV2 pre-defined by the performing laboratory) and a COV adjusted by age, weight and sex (COV3 > 31 IU/L for women and > 44 IU/L and men > 42 IU/L and > 66 IU/L with a BMI > 23). Logistic regression analysis was performed to determine risk factors for elevated [ALT]s Results: Mean [ALT]s values were 30.14 I U/L in men and 22.03 IU/L in women. The observed prevalence of abnormal [ALT]s defined by different COV were 38%, 11.5%, and 8.1% for COV1, COV2 and COV3 respectively. Variables independently associated to abnormal [ALT]s in a multivariate analysis were the following: serum gamma-glutamyl-transpeptidase (OR: 1.055 [95% CI 1.033-1.078]) and body mass index (OR:1.13 [95% CI 1.09-1.17]). Variables inversely associated with abnormal [ALT]s (COV1) were mole gender (OR-.0.976 [95% CI 0.96-0.99) and HDL-cholesterol (OR:0979 [95% CI 0.96-0.99]). Conclusions: Independently of the COV used, Chilean population exhibits a high prevalence of abnormal [ALT]s which may reflect a significant burden of liver disease. Non-alcoholic fatty liver disease could be a major contributor to elevated [ALT]s considering the association of abnormal [ALT]s and metabolic variables.