Aprendizaje en investigación clínica: experiencia de enseñanza híbrida con estudiantes de medicina / Learning in Clinical Research: Hybrid Teaching Experience with Medical Students

Introducción: la pandemia de COVID-19 indujo un cambio en nuestro sistema de salud y de educación. Los programas formativos también tuvieron que adaptarse y exigieron un cambio rápido. Objetivos: describir una experiencia educativa de enseñanza virtual/híbrida en investigación clínica, entre docentes del Servicio de Clínica de un hospital universitario y estudiantes de Medicina de una institución privada, que participaron del Programa ESIN (EStudiantes en INvestigación). Metodología: los contenidos y las estrategias educativas incluyeron las clases teóricas audiograbadas o videograbadas (asincrónicas y autoadministradas), el aprendizaje basado en proyectos, los talleres prácticos (encuentros sincrónicos virtuales y grupales), mediante la adopción de modelos de aprendizaje como el aula invertida, y la tutoría individual entre docente-estudiante. Los datos se recopilaron mediante la observación en contextos académicos, y basándonos en elementos de encuestas anónimas de satisfacción, previo consentimiento informado de los participantes. Resultados: participaron 14 estudiantes, 6 durante el año 2021 y 8 durante 2022. Todas mujeres y estudiantes de medicina (50% de cuarto año, 35% de sexto año y 15% de quinto año). Las técnicas implementadas favorecieron la participación y promovieron el aprendizaje activo, basado en proyectos. Mencionaron aspectos positivos como el enfoque académico práctico, la disponibilidad del equipo docente para atender cualquier duda, el tiempo y el entusiasmo por enseñar y fomentar la participación. Los videos teóricos resultaron útiles como herramientas de repaso, y los encuentros grupales fueron especialmente valorados, si bien los encuentros individuales fueron destacados como ayuda y apoyo previo a los congresos científicos. En general, manifestaron que fue una experiencia enriquecedora que demostró que se puede lograr lo que se creía imposible. Todas participaron activamente de al menos un congreso científico, y el 50% resultó coautora de una publicación académica. Conclusión: los estudiantes asumieron compromisos y responsabilidades, e incorporaron competencias y habilidades en la implementación y en la difusión de los proyectos. Esta experiencia educativa facilitó que el tiempo de clase pudiera optimizarse para intercambio, discusión y dudas. Los recursos producidos, las actividades desarrolladas y los contenidos abordados quedan disponibles a nivel institución. (AU)

Introduction: the COVID-19 pandemic brought about a change in our health and education system. Training programs also had to adapt and required rapid change. Objectives: to describe an educational experience of virtual/hybrid teaching in clinical research between teachers of the Clinical Service of a university hospital and medical students of a private institution who participated in the ESIN Program (Students in Research). Methodology: the contents and educational strategies included audio or videotaped lectures (asynchronous and self-administered), project-based learning, practical workshops (virtual and group synchronous meetings) by adopting learning models such as the inverted classroom, and individual tutoring between teacher and student. We gathered the data through observation in academic contexts and based on elements of anonymous satisfaction surveys, with prior informed consent of participants. Results: fourteen students participated, six in 2021 and eight in 2022. All were women and medical students (50% fourth year, 35% sixth year, and 15% fifth year). The techniques implemented favored participation and promoted active, project-based learning. They mentioned positive aspects such as the practical academic approach, the availability of the teaching team for any doubts, the time and enthusiasm for teaching, and encouraging participation. The theory videos were a valuable review tool, and team meetings received high praise even if the one-on-one meetings received much attention as help and support before the scientific congresses. In general, they stated that it was an enriching experience that showed that you can achieve what you thought impossible. All of them actively participated in at least one scientific congress, and 50% were co-authors of an academic publication. Conclusion: the students assumed commitments and responsibilities and incorporated competencies and skills in project implementation and dissemination. This educational experience helped to optimize class time for exchange, discussion, and doubts. The resources produced, the activities developed, and the contents addressed are now available at the institutional level. (AU)

Prevalencia de diabetes, características epidemiológicas y complicaciones vasculares / Prevalence of diabetes, epidemiological characteristics and vascular complications

Resumen Objetivo: Estimar la prevalencia de diabetes en atención ambulatoria y describir sus características epidemiológicas, comorbilidades y complicaciones vasculares relacionadas. Método: Corte transversal que incluyó la totalidad de adultos afiliados a la prepaga del Hospital Italiano de Buenos Aires en marzo de 2019, Argentina. Resultados: La prevalencia global de diabetes resultó del 8.5% con intervalo de confianza del 95% (IC95%): 8.3-8.6 (12,832 de un total de 150,725 afiliados). El estrato etario con mayor prevalencia fue el grupo entre 65 y 80 años, con un 15.7% (IC95%: 15.3-16.1). Las personas con diabetes presentaban una media de edad de 70 años (desviación estándar: 14), el 52% eran mujeres, y los factores de riesgo cardiovasculares más frecuentemente asociados fueron: dislipidemia (88%), hipertensión arterial (74%) y obesidad (55%). En relación con el control metabólico, el 60% tenía al menos una hemoglobina glucosilada medida en el último año, siendo el 70% de estas menores al 7%. Casi el 80% tiene medido el colesterol vinculado a lipoproteínas de baja densidad (c-LDL) al menos una vez en los últimos dos años, de ellos el 55% presentaba un valor de c-LDL igual o menor a 100 mg/dl. Las complicaciones macrovasculares presentes en orden de frecuencia fueron: infarto agudo de miocardio (11%), accidente cerebrovascular (8%) y enfermedad vascular periférica (4%); mientras que las complicaciones microvasculares resultaron ser neuropatía diabética (4%) y retinopatía (2%). El 7% tuvo pie diabético, con menos del 1% de amputaciones. Conclusiones: La diabetes representa un problema prevalente, incluso en pacientes ancianos. Esta población sigue presentando un elevado riesgo cardiovascular, con escaso cumplimiento de objetivos terapéuticos.

Abstract Objective: To estimate prevalence of diabetes in outpatient care and to describe its epidemiological characteristics, comorbidities, and related vascular complications. Methods: Observational cross-sectional study which included all adults affiliated from a private insurance health plan on March 2019, at Hospital Italiano de Buenos Aires, from Argentina. Results: The global prevalence of diabetes resulted in 8.5% with 95% CI 8.3-8.6 (12,832 out of a total of 150,725 affiliates). The age stratum with the highest prevalence was the group between 65 and 80 years old with 15.7% (95% CI 15.3-16.1). People with diabetes had a mean age of 70 years (SD 14), 52% were women, and the most frequently associated cardiovascular risk factors were: dyslipidaemia (88%), arterial hypertension (74%) and obesity (55%). In relation to metabolic control, 60% had at least one glycosylated hemoglobin measured in the last year, 70% of which were less than 7%. Almost 80% have LDL measured at least once in the last 2 years, 55% of them had an LDL value equal to or less than 100 mg/dl. The macrovascular complications present in order of frequency were: acute myocardial infarction (11%), cerebrovascular accident (8%) and peripheral vascular disease (4%); while the microvascular complications were found to be diabetic neuropathy (4%) and retinopathy (2%). 7% had diabetic foot, with less than 1% amputations. Conclusion: Diabetes represents a prevalent problem, even in elderly patients. This population continues to present a high cardiovascular risk, with little compliance with therapeutic goals.

Prevalence of diabetes, epidemiological characteristics and vascular complications.

OBJECTIVE: To estimate prevalence of diabetes in outpatient care and to describe its epidemiological characteristics, comorbidities, and related vascular complications. METHODS: Observational cross-sectional study which included all adults affiliated from a private insurance health plan on March 2019, at Hospital Italiano de Buenos Aires, from Argentina. RESULTS: The global prevalence of diabetes resulted in 8.5% with 95% CI 8.3-8.6 (12,832 out of a total of 150,725 affiliates). The age stratum with the highest prevalence was the group between 65 and 80 years old with 15.7% (95% CI 15.3-16.1). People with diabetes had a mean age of 70 years (SD 14), 52% were women, and the most frequently associated cardiovascular risk factors were: dyslipidaemia (88%), arterial hypertension (74%) and obesity (55%). In relation to metabolic control, 60% had at least one glycosylated hemoglobin measured in the last year, 70% of which were less than 7%. Almost 80% have LDL measured at least once in the last 2 years, 55% of them had an LDL value equal to or less than 100 mg/dl. The macrovascular complications present in order of frequency were: acute myocardial infarction (11%), cerebrovascular accident (8%) and peripheral vascular disease (4%); while the microvascular complications were found to be diabetic neuropathy (4%) and retinopathy (2%). 7% had diabetic foot, with less than 1% amputations. CONCLUSION: Diabetes represents a prevalent problem, even in elderly patients. This population continues to present a high cardiovascular risk, with little compliance with therapeutic goals.

OBJETIVO: Estimar la prevalencia de diabetes en atención ambulatoria y describir sus características epidemiológicas, comorbilidades y complicaciones vasculares relacionadas. MÉTODO: Corte transversal que incluyó la totalidad de adultos afiliados a la prepaga del Hospital Italiano de Buenos Aires en marzo de 2019, Argentina. RESULTADOS: La prevalencia global de diabetes resultó del 8.5% con intervalo de confianza del 95% (IC95%): 8.3-8.6 (12,832 de un total de 150,725 afiliados). El estrato etario con mayor prevalencia fue el grupo entre 65 y 80 años, con un 15.7% (IC95%: 15.3-16.1). Las personas con diabetes presentaban una media de edad de 70 años (desviación estándar: 14), el 52% eran mujeres, y los factores de riesgo cardiovasculares más frecuentemente asociados fueron: dislipidemia (88%), hipertensión arterial (74%) y obesidad (55%). En relación con el control metabólico, el 60% tenía al menos una hemoglobina glucosilada medida en el último año, siendo el 70% de estas menores al 7%. Casi el 80% tiene medido el colesterol vinculado a lipoproteínas de baja densidad (c-LDL) al menos una vez en los últimos dos años, de ellos el 55% presentaba un valor de c-LDL igual o menor a 100 mg/dl. Las complicaciones macrovasculares presentes en orden de frecuencia fueron: infarto agudo de miocardio (11%), accidente cerebrovascular (8%) y enfermedad vascular periférica (4%); mientras que las complicaciones microvasculares resultaron ser neuropatía diabética (4%) y retinopatía (2%). El 7% tuvo pie diabético, con menos del 1% de amputaciones. CONCLUSIONES: La diabetes representa un problema prevalente, incluso en pacientes ancianos. Esta población sigue presentando un elevado riesgo cardiovascular, con escaso cumplimiento de objetivos terapéuticos.

Rootstock-scion interaction affecting citrus response to CTV infection: a proteomic view.

Citrus tristeza virus (CTV) is the causal agent of various diseases with dramatic effects on citrus crops worldwide. Most Citrus species, grown on their own roots, are symptomless hosts for many CTV isolates. However, depending on different scion-rootstock combination, CTV infection should result in distinct syndromes, being 'tristeza' the more severe one, leading to a complete decline of the susceptible plants in a few weeks. Transcriptomic analyses revealed several genes involved either in defense response, or systemic acquired resistance, as well as transcription factors and components of the phosphorylation cascades, to be differentially regulated during CTV infection in Citrus aurantifolia species. To date little is known about the molecular mechanism of this host-pathogen interaction, and about the rootstock effect on citrus response to CTV infection. In this work, the response to CTV infection has been investigated in tolerant and susceptible scion-rootstock combinations by two-dimensional gel electrophoresis (2DE). A total of 125 protein spots have been found to be differently accumulated and/or phosphorylated between the two rootstock combinations. Downregulation in tolerant plants upon CTV infection was detected for proteins involved in reactive oxygen species (ROS) scavenging and defense response, suggesting a probable acclimation response able to minimize the systemic effects of virus infection. Some of these proteins resulted to be modulated also in absence of virus infection, revealing a rootstock effect on scion proteome modulation. Moreover, the phospho-modulation of proteins involved in ROS scavenging and defense response, further supports their involvement either in scion-rootstock crosstalk or in the establishment of tolerance/susceptibility to CTV infection.

Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells.

Bacterial lipopolysaccharide (LPS) stimulates Kupffer cells and participates in the pathogenesis of alcohol-induced liver injury. However, it is unknown whether LPS directly affects hepatic stellate cells (HSCs), the main fibrogenic cell type in the injured liver. This study characterizes LPS-induced signal transduction and proinflammatory gene expression in activated human HSCs. Culture-activated HSCs and HSCs isolated from patients with hepatitis C virus-induced cirrhosis express LPS-associated signaling molecules, including CD14, toll-like receptor (TLR) 4, and MD2. Stimulation of culture-activated HSCs with LPS results in a rapid and marked activation of NF-kappaB, as assessed by in vitro kinase assays for IkappaB kinase (IKK), IkappaBalpha steady-state levels, p65 nuclear translocation, NF-kappaB-dependent luciferase reporter gene assays, and electrophoretic mobility shift assays. Lipid A induces NF-kappaB activation in a similar manner. Both LPS- and lipid A-induced NF-kappaB activation is blocked by preincubation with either anti-TLR4 blocking antibody (HTA125) or Polymyxin B. Lipid A induces NF-kappaB activation in HSCs from TLR4-sufficient (C3H/OuJ) mice but not from TLR4-deficient (C3H/HeJ) mice. LPS also activates c-Jun N-terminal kinase (JNK), as assessed by in vitro kinase assays. LPS up-regulates IL-8 and MCP-1 gene expression and secretion. LPS-induced IL-8 secretion is completely inhibited by the IkappaB super repressor (Ad5IkappaB) and partially inhibited by a specific JNK inhibitor, SP600125. LPS also up-regulates cell surface expression of ICAM-1 and VCAM-1. In conclusion, human activated HSCs utilize components of TLR4 signal transduction cascade to stimulate NF-kappaB and JNK and up-regulate chemokines and adhesion molecules. Thus, HSCs are a potential mediator of LPS-induced liver injury.

IKK beta and phosphatidylinositol 3-kinase/Akt participate in non-pathogenic Gram-negative enteric bacteria-induced RelA phosphorylation and NF-kappa B activation in both primary and intestinal epithelial cell lines.

Pathogenic and enteroinvasive bacteria have been shown to trigger the I kappa B/NF-kappa B transcriptional system and proinflammatory gene expression in epithelial cells. In this study, we investigated the molecular mechanism of the commensal Gram-negative Bacteroides vulgatus-induced NF-kappa B signal transduction in intestinal epithelial cells (IEC). We report that B. vulgatus induced interleukin-1 receptor-associated kinase-1 degradation, I kappa B alpha phosphorylation/degradation, RelA and Akt phosphorylation, as well as NF-kappa B DNA binding and NF-kappa B transcriptional activity in rat non-transformed IEC-6 cells. B. vulgatus- but not interleukin-1 beta-mediated NF-kappa B transcriptional activity was inhibited by dominant negative (dn) toll-like receptor 4. Of importance, B. vulgatus induced I kappa B alpha phosphorylation/degradation and IKK alpha/beta and RelA phosphorylation in primary IEC derived from germ-free or mono-associated HLA-B27 transgenic and wild type rats, demonstrating the physiological relevance of non-pathogenic bacterial signaling in IEC. Adenoviral delivery of dn IKK beta or treatment with wortmannin inhibited B. vulgatus-induced endogenous RelA Ser-536 and GST-p65TAD (Ser-529/Ser-536) phosphorylation as well as NF-kappa B transcriptional activity in IEC-6 cells, suggesting a critical role of IKK beta and phosphatidylinositol 3-kinase/Akt in bacteria-induced RelA phosphorylation and NF-kappa B activation. Interestingly, B. vulgatus-induced I kappa B alpha degradation and NF-kappa B transcriptional activity in IEC transwell cultures were inhibited in the presence of lymphocytes. We propose that non-pathogenic B. vulgatus activates the NF-kappa B signaling pathway through both I kappa B degradation and RelA phosphorylation but that immune cells mediate tolerance of IEC to this commensal bacteria.

Differential requirement for NF-kappaB-inducing kinase in the induction of NF-kappaB by IL-1beta, TNF-alpha, and Fas.

In this study, we examined the role of the nuclear factor-kappaB (NF-kappaB)-inducing kinase (NIK) in distinct signaling pathways leading to NF-kappaB activation. We show that a dominant-negative form of NIK (dnNIK) delivered by adenoviral (Ad5dnNIK) vector inhibits Fas-induced IkappaBalpha phosphorylation and NF-kappaB-dependent gene expression in HT-29 and HeLa cells. Interleukin (IL)-1beta- and tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB activation and kappaB-dependent gene expression are inhibited in HeLa cells but not in Ad5dnNIK-infected HT-29 cells. Moreover, Ad5dnNIK failed to sensitize HT-29 cells to TNF-alpha-induced apoptosis at an early time point. However, cytokine- and Fas-induced signals to NF-kappaB are finally integrated by the IkappaB kinase (IKK) complex, since IkappaBalpha phosphorylation, NF-kappaB DNA binding activity, and IL-8 gene expression were strongly inhibited in HT-29 and HeLa cells overexpressing dominant-negative IKKbeta (Ad5dnIKKbeta). Our findings support the concept that cytokine signaling to NF-kappaB is redundant at the level of NIK. In addition, this study demonstrates for the first time the critical role of NIK and IKKbeta in Fas-induced NF-kappaB signaling cascade.