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BACKGROUND: About 80% of cardiovascular diseases (including heart failure [HF]) occur in low-income and developing countries. However, most clinical trials are conducted in developed countries. HYPOTHESIS: The American Registry of Ambulatory or Acutely Decompensated Heart Failure (AMERICCAASS) aims to describe the sociodemographic characteristics of HF, comorbidities, clinical presentation, and pharmacological management of patients with ambulatory or acutely decompensated HF in America. METHODOLOGY: Descriptive, observational, prospective, and multicenter registry, which includes patients >18 years with HF in an outpatient or hospital setting. Collected information is stored in the REDCap electronic platform. Quantitative variables are defined according to the normality of the variable using the Shapiro-Wilk test. RESULTS: This analysis includes data from the first 1000 patients recruited. 63.5% were men, the median age of 66 years (interquartile range 56.7-75.4), and 77.6% of the patients were older than 55 years old. The percentage of use of the four pharmacological pillars at the time of recruitment was 70.7% for beta-blockers (BB), 77.4% for angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB II)/angiotensin receptor-neprilysin inhibitor (ARNI), 56.8% for mineralocorticoid receptor antagonists (MRA), and 30.7% for sodium-glucose cotransporter type-2 inhibitors (SGLT2i). The main cause of decompensation in hospitalized patients was HF progression (64.4%), and the predominant hemodynamic profile was wet-warm (68.3%). CONCLUSIONS: AMERICCAASS is the first continental registry to include hospitalized or outpatient patients with HF. Regarding optimal medical therapy, approximately a quarter of the patients still need to receive BB and ACEI/ARB/ARNI, less than half do not receive MRA, and more than two-thirds do not receive SGLT2i.
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Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Cardíaca , Masculino , Humanos , Estados Unidos/epidemiología , Anciano , Persona de Mediana Edad , Femenino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Estudios Prospectivos , Volumen Sistólico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Sistema de Registros , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/uso terapéuticoRESUMEN
DNA double-strand breaks (DSBs) are among the most deleterious lesions that threaten genome integrity. To address DSBs, eukaryotic cells of model organisms have evolved a complex network of cellular pathways that are able to detect DNA damage, activate a checkpoint response to delay cell cycle progression, recruit the proper repair machinery, and resume the cell cycle once the DNA damage is repaired. Cell cycle checkpoints are primarily regulated by the apical kinases ATR and ATM, which are conserved throughout the eukaryotic kingdom. Trypanosoma brucei is a divergent pathogenic protozoan parasite that causes human African trypanosomiasis (HAT), a neglected disease that can be fatal when left untreated. The proper signaling and accuracy of DNA repair is fundamental to T. brucei not only to ensure parasite survival after genotoxic stress but also because DSBs are involved in the process of generating antigenic variations used by this parasite to evade the host immune system. DSBs trigger a strong DNA damage response and efficient repair process in T. brucei, but it is unclear how these processes are coordinated. Here, by knocking down ATR in T. brucei using two different approaches (conditional RNAi and an ATR inhibitor), we show that ATR is required to mediate intra-S and partial G1/S checkpoint responses. ATR is also involved in replication fork stalling, is critical for H2A histone phosphorylation in a small group of cells and is necessary for the recruitment and upregulation of the HR-mediated DNA repair protein RAD51 after ionizing radiation (IR) induces DSBs. In summary, this work shows that apical ATR kinase plays a central role in signal transduction and is critical for orchestrating the DNA damage response in T. brucei.
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Introducción: el pregrado en instrumentación quirúrgica (IQ) de la Universidad de Antioquia (Colombia) concibe las prácticas académicas como un componente fundamental en la formación de los estudiantes; estas incluyen actividades como talleres experimentales, observación dirigida y asistencia en áreas quirúrgicas. La emergencia sanitaria desatada por la pandemia del COVID-19 disminuyó en forma drástica las oportunidades de práctica asistencial en instituciones de salud. Material y método: se posibilitó la participación de los estudiantes de IQ en un entorno formativo nuevo para la realización de prácticas, en el LivingLab Telesalud de la facultad de medicina de la Universidad de Antioquia con atención en la línea telefónica 123. Objetivo: de comprender esta experiencia de los estudiantes de IQ en la atención de la pandemia por COVID-19, se realizó una investigación con enfoque cualitativo que consideró la consulta a fuentes vivas y documentales. Resultados y conclusiones: los resultados indican que la práctica favoreció la formación integral del futuro instrumentador quirúrgico, asunto que se soporta en la identificación de dimensiones pedagógicas, curriculares y didácticas que tuvieron lugar en la experiencia; también se evidenciaron algunas oportunidades de mejora que pueden considerarse para futuros procesos formativos.
Introduction: the undergraduate surgical instrumentation (SI) program at Universidad de Antioquia (Colombia) defines academic practices as a fundamental component of training students, by means of activities such as experimental workshops, guided observation and surgical assistance. The health emergency unleashed by the COVID-19 pandemic drastically reduced the opportunities for clinical practice in healthcare institutions. Materials and methods: the participation of SI students was made possible in a new training practice environment using the Telesalud LivingLab of Universidad de Antioquia School of Medicine, through phone number 123. Objetive: a qualitative approach research was carried out to understand this experience in SI students, by consulting live and documentary sources. Results and conclusions: the results indicate that this practice modality favored the comprehensive training of the future surgical technologist. The latter is supported by pedagogical, curricular and didactic dimensions that took place during the experience. Several improvement opportunities, which can be useful in future training processes, were also evidenced.
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HumanosRESUMEN
One of the most important mechanisms for repairing double-strand breaks (DSBs) in model eukaryotes is homologous recombination (HR). Although the genes involved in HR have been found in Trypanosoma brucei and studies have identified some of the proteins that participate in this HR pathway, the recruitment kinetics of the HR machinery onto DNA during DSB repair have not been clearly elucidated in this organism. Using immunofluorescence, protein DNA-bound assays, and DNA content analysis, we established the recruitment kinetics of the HR pathway in response to the DSBs generated by ionizing radiation (IR) in procyclic forms of T. brucei. These kinetics involved the phosphorylation of histone H2A and the sequential recruitment of the essential HR players Exo1, RPA, and Rad51. The process of DSB repair took approximately 5.5 hours. We found that DSBs led to a decline in the G2/M phase after IR treatment, concomitant with cell cycle arrest in the G1/S phase. This finding suggests that HR repairs DSBs faster than the other possible DSB repair processes that act during the G1/S transition. Taken together, these data suggest that the interplay between DNA damage detection and HR machinery recruitment is finely coordinated, allowing these parasites to repair DNA rapidly after DSBs during the late S/G2 proficient phases.
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Recombinación Homóloga/efectos de la radiación , Radiación Ionizante , Trypanosoma brucei brucei/metabolismo , Fragmentación del ADN/efectos de la radiación , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de la radiación , Histonas/metabolismo , Fosforilación/efectos de la radiación , Proteínas Protozoarias/metabolismo , Reparación del ADN por Recombinación/efectos de la radiación , Proteína de Replicación A/genética , Proteína de Replicación A/metabolismo , Puntos de Control de la Fase S del Ciclo Celular/efectos de la radiación , Trypanosoma brucei brucei/efectos de la radiaciónRESUMEN
Detection of genetic exchange has been a limiting factor to deepen the knowledge on the mechanisms by which Trypanosoma cruzi is able to generate progeny and genetic diversity. Here we show that incorporation of halogenated thymidine analogues, followed by immunostaining, is a reliable method not only to detect T. cruzi fused-cell hybrids, but also to quantify their percentage in populations of this parasite. Through this approach, we were able to detect and quantify fused-cell hybrids of T. cruzi clones CL Brener and Y. Given the increased detection of fused-cell hybrids in naturally-occurring hybrid CL Brener strain, which displays increased levels of RAD51 and BRCA2 transcripts, we further investigated the role of Rad51 - a recombinase involved in homologous recombination - in the process of genetic exchange. We also verified that the detection of fused-cell hybrids in T. cruzi overexpressing RAD51 is increased when compared to wild-type cells, suggesting a key role for Rad51 either in the formation or in the stabilization of fused-cell hybrids in this organism.
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Recombinación Homóloga/fisiología , Proteínas Protozoarias/metabolismo , Recombinasa Rad51/metabolismo , Trypanosoma cruzi/enzimología , Proteínas Protozoarias/genética , Recombinasa Rad51/genética , Trypanosoma cruzi/genéticaRESUMEN
Resumen La infección por SARS-CoV2 es una pandemia. Se creía que el primer caso de esta enfermedad ocurrió el 8 de diciembre de 2019 en la provincia de Hubei en China, aunque posteriormente se indicó que el primer caso confirmado por laboratorio ocurrió el 1.( de diciembre de 2019 ante la presencia de un brote de neumonía en 59 pacientes sospechosos en un mercado local de mariscos en Wuhan. No solo produce patología respiratoria, con frecuencia compremete el sistema cardiovascular ya que produce lesión miocárdica, miocarditis, y, con cierta frecuencia, aumenta la descompensación de enfermedades cardiovasculares preestablecidas. En este artículo se trata de dilucidar el componente cardiovascular hasta ahora existente en la literatura y se sugieren algunos pasos a seguir en pacientes con estas enfermedades, acorde con la evidencia actual.
Abstract Infection due to SARS-CoV2 is a pandemic. It is believed that the first case occurred on 8 December 2019 in Hubei province in China, although it was later indicated that the first laboratory-confirmed case occurred on 1 December 2019 due to the presence of an outbreak of suspected pneumonia in 59 patients in a shellfish market in Wuhan. It not only caused a respiratory disease, it often compromised the cardiovascular system since it produces a myocardial lesion, myocarditis, and, less often, increased the decompensation of pre-established cardiovascular diseases. An attempt is made in this article to elucidate the cardiovascular component presented in the current literature, and to suggest some steps to follow in patients with these diseases in accordance with the current evidence.
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Humanos , Masculino , Femenino , Coronavirus , Insuficiencia Cardíaca , Neumonía , Síndrome de Dificultad Respiratoria del Recién Nacido , Daño por Reperfusión Miocárdica , Síndrome Respiratorio Agudo Grave , MiocarditisRESUMEN
La Facultad de Medicina de la Universidad de Antioquia ha aplicado la estrategia didáctica de Aprendizaje Basado en Problemas (ABP) en el proceso de la renovación curricular que inició en el año 2000. Este artículo analiza la función de los tutores, la formación docente y la percepción de los estudiantes y los profesores sobre el desempeño de los tutores en el ABP. Se basa en un estudio cualitativo más amplio, tendiente a la evaluación del impacto de esa didáctica en el currículo de Medicina de la institución. Se hizo una triangulación de fuentes con datos suministrados por actores participantes en el ABP (estudiantes, tutores y coordinadores), los artículos de análisis sobre la estrategia producidos por profesores de la Facultad y la información obtenida de entrevistas con expertos en el tema. Se encontró que esa didáctica ha estimulado la adopción de nuevos roles entre los docentes y hay satisfacción entre los estudiantes con esta manera de aprender y de relacionarse con los profesores. Se hallaron debilidades en la formación de ABP entre los docentes, lo cual genera inconsistencias en el desarrollo de la estrategia. Se recomienda ampliar y profundizar la capacitación para fortalecer la función del tutor, así como establecer espacios comunes para compartir prácticas y discursos.
In the context of the curricular renewal undertaken since 2000, the Faculty of Medicine (University of Antioquia, Medellín, Colombia) has implemented the teaching strategy Problem Based Learning (PBL). This article discusses the role of PBL tutors, teacher training and the perception of students and teachers on the performance of tutors. The study is part of a larger qualitative study aimed at evaluating the impact of PBL on medical curriculum at this institution. A triangulation of sources was used. They were: data provided by PBL participants (students, tutors and coordinators), analysis of articles about the strategy written by teachers of this Faculty and information obtained from experts in the topic. It was found that PBL has stimulated the adoption of new roles amoung teachers, and that students are satisfied with this way of learning and interacting with teachers. However, there are still weaknesses in PBL training among teachers, which generate inconsistencies in the development of the strategy. It is recommended to broaden and deepen teacher training in order to strengthen the role of tutors in PBL, as well as to establish common spaces to share practices and discourses.
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Humanos , Educación Médica , Docentes Médicos , Aprendizaje , Aprendizaje Basado en Problemas , Estudiantes de Medicina , Facultades de MedicinaRESUMEN
A partir de la reforma curricular en la Facultad de Medicina de la Universidad de Antioquia (Medellín, Colombia) se implementó el Aprendizaje Basado en Problemas como una de las estrategias didácticas activas para favorecer en los estudiantes el liderazgo en su proceso de aprendizaje. Para evaluar el impacto que ha tenido esta estrategia en el currículo, se hizo una investigación con enfoque explicativo y comprensivo. Se triangularon los resultados obtenidos de entrevistas a expertos, encuestas a actores de la estrategia y documentos producidos por profesores de la Facultad de Medicina. Los resultados muestran que hay satisfacción por parte de los actores con el uso de la estrategia para la formación integral del estudiante y que además se reconocen otras opciones didácticas para el desarrollo curricular.
Ever since curricular reforms were made at the Faculty of Medicine (University of Antioquia, Medellín, Colombia), Problem Based Learning has been implemented as one of the active didactic strategies that may help students to lead their process of learning. To assess the impact of this strategy on the curriculum, a qualitative research was carried out. All the results: interviews with experts, surveys with the participants in the strategy and documents written by professors of the medical school were triangulated. Findings show that participants are satisfied with the use of the strategy and acknowledge its importance in the integral formation of students. However, PBL is not the only teaching option to be used in our curriculum.