32 research outputs found

    Características morfológicas del círculo arterial del cerebro en fallecidos por infarto cerebral

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    Se realiza un estudio en el Hospital General Docente “Dr. Agostinho Neto” de Guantánamo con el objetivo de describir características morfométricas del círculo arterial del cerebro en 30 fallecidos por infarto cerebral, de febrero a julio de 2008. La información fue procesada utilizando paquete estadístico SPSS V. 10.0. Se determina frecuencia absoluta, porcentaje de variables cualitativas, media y desviación estándar para longitud de arterias cerebrales que conforman el círculo del cerebro. Predomina el sexo masculino, grupo de edades de 80 años y más, color de piel mestizo, antecedentes de hipertensión arterial y fumadores. No se muestra diferencias estadísticamente significativas al comparar valores de longitud media de arterias que forman círculo arterial del cerebro, El círculo arterial de los fallecidos estaba modificado manifestándose en el aspecto delgado de las arterias que aparecieron mayoritariamente en arterias comunicantes posteriores derechas, en fallecidos del sexo femenino, en mestizos y fumadores

    Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

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    Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Nervio ignorado: nervio craneal cero

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    Since 1998 the international anatomical nomenclature recognizes the existence of the terminal nerve, however, is ignored by classical anatomy and forgotten in texts and medical training programs. This motivates the current study with the aim to describe the morphological and functional characteristics of this cranial nerve, highlighting its role in the body. An extensive literature review of the anatomical literature, research and scientific publications is done; as a conclusion that the cranial nerve zero or a nerve terminal is poorly understood but has important functions related to olfaction, reproductive behavior and secretes a powerful sex hormone (GnRH) in the blood.Desde 1998 la nomenclatura anatómica internacional reconoce la existencia del nervio terminal, sin embargo, es ignorado por los clásicos de la anatomía y olvidado en los textos y programas de instrucción médica. Esto motiva el actual estudio con el objetivo de describir las características morfofuncionales de este nervio craneal, destacando el papel que juega en el organismo. Para ello se realiza una amplia revisión bibliográfica de la literatura anatómica, trabajos de investigación y publicaciones científicas; pudiendo concluir, que el nervio craneal cero o terminal es un nervio poco conocido pero que tiene importantes funciones relacionadas con la olfacción y la conducta reproductivaya que segrega una hormona sexual poderosa (GnRH) en la sangre

    Nervio ignorado: nervio craneal cero

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    Since 1998 the international anatomical nomenclature recognizes the existence of the terminal nerve, however, is ignored by classical anatomy and forgotten in texts and medical training programs. This motivates the current study with the aim to describe the morphological and functional characteristics of this cranial nerve, highlighting its role in the body. An extensive literature review of the anatomical literature, research and scientific publications is done; as a conclusion that the cranial nerve zero or a nerve terminal is poorly understood but has important functions related to olfaction, reproductive behavior and secretes a powerful sex hormone (GnRH) in the blood.Desde 1998 la nomenclatura anatómica internacional reconoce la existencia del nervio terminal, sin embargo, es ignorado por los clásicos de la anatomía y olvidado en los textos y programas de instrucción médica. Esto motiva el actual estudio con el objetivo de describir las características morfofuncionales de este nervio craneal, destacando el papel que juega en el organismo. Para ello se realiza una amplia revisión bibliográfica de la literatura anatómica, trabajos de investigación y publicaciones científicas; pudiendo concluir, que el nervio craneal cero o terminal es un nervio poco conocido pero que tiene importantes funciones relacionadas con la olfacción y la conducta reproductivaya que segrega una hormona sexual poderosa (GnRH) en la sangre

    Ignored nerve: Cranial nerve zero

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    Desde 1998 la nomenclatura anatómica internacional reconoce la existencia del nervio terminal, sin embargo, es ignorado por los clásicos de la anatomía y olvidado en los textos y programas de instrucción médica. Esto motiva el actual estudio con el objetivo de describir las características morfofuncionales de este nervio craneal, destacando el papel que juega en el organismo. Para ello se realiza una amplia revisión bibliográfica de la literatura anatómica, trabajos de investigación y publicaciones científicas; pudiendo concluir, que el nervio craneal cero o terminal es un nervio poco conocido pero que tiene importantes funciones relacionadas con la olfacción y la conducta reproductivaya que segrega una hormona sexual poderosa (GnRH) en la sangre.Since 1998 the international anatomical nomenclature recognizes the existence of the terminal nerve, however, is ignored by classical anatomy and forgotten in texts and medical training programs. This motivates the current study with the aim to describe the morphological and functional characteristics of this cranial nerve, highlighting its role in the body. An extensive literature review of the anatomical literature, research and scientific publications is done; as a conclusion that the cranial nerve zero or a nerve terminal is poorly understood but has important functions related to olfaction, reproductive behavior and secretes a powerful sex hormone (GnRH) in the blood

    Importancia del cadáver para la investigación científica en Anatomía Humana y en la formación del profesional de la salud

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    La Anatomía es una ciencia muy amplia en la cual los medios de enseñanza son imprescindibles para el aprendizaje pues con su utilización los resultados son superiores, fundamentalmente, los de origen natural. Por su importancia se realiza esta revisión bibliográfica, además, de que hay que considerar el  creciente número de estudiantes que ingresan en los centros de Educación Médica Superior y, por ende, mayor será la cantidad de cadáveres y vísceras necesarios en los laboratorios de anatomía. Siempre teniendo presente y respetando, antes de utilizar el cadáver con fines de investigación, la decisión en vida de esa persona de donar su cuerpo o no para que sea utilizado como pieza anatómica

    La repitencia: un reto para la Educación Médica guantanamera

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    A descriptive cross-sectional study was carried out during the first semester of the academic year 2016/2017, with the objective of analyzing the academic results of the students repeating in this discipline, in the Faculty of Medical Sciences of Guantanamo. The universe was composed of 165 students who were repeaters of the first year of the medical school, 137 students were used as sample, theoretical and empirical methods were used, a survey was applied to students with informed consent and interviewed teachers, obtaining as results, almost half of the repeating students were disapproved in the BBM discipline in the first semester of the current course, with great influence of those who had to study the 3 subjects of this discipline. The lack of motivation and a carefree attitude towards the study were the main causes to which the repeating students attribute the low academic performance. The teachers consider that there is a discrepancy between the previous knowledge that the university requires of its students and those that in fact they acquire from the preuniversity and that the student's motivation for the career is cause of the academic performance.Se realizó un estudio descriptivo transversal durante el primer semestre del curso 2016-2017, con el objetivo de analizar los resultados académicos de los estudiantes repitentes, en la Facultad de Ciencias Médicas de Guantánamo. El universo estuvo integrado por 165 estudiantes repitentes del primer año de la carrera de Medicina. Se utilizó como muestra 137 estudiantes. Se emplearon métodos teóricos y empíricos, se aplicaron encuestas a estudiantes previo consentimiento informado y entrevista a profesores. Se obtuvo como resultados, que casi la mitad de los estudiantes repitentes resultaron reprobados en la disciplina Bases Biológicas de la Medicina en el primer semestre del presente curso, con gran influencia de los que debían cursar las tres asignaturas de esta disciplina. La desmotivación y una actitud despreocupada frente al estudio fueron las principales causas a que atribuyen los estudiantes repitentes el bajo rendimiento académico. Los docentes consideran que existe discrepancia entre los saberes previos que la universidad requiere de sus alumnos y los que en realidad éstos traen del preuniversitario y que la desmotivación del estudiante por la carrera es causa del rendimiento académico
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