RESUMO
Myotonic dystrophy type 1 is a complex disease caused by a genetically unstable CTG repeat expansion in the 3'-untranslated region of the DMPK gene. Age-dependent, tissue-specific somatic instability has confounded genotype-phenotype associations, but growing evidence suggests that it also contributes directly toward disease progression. Using a well-characterized clinical cohort of DM1 patients from Costa Rica, we quantified somatic instability in blood, buccal cells, skin and skeletal muscle. Whilst skeletal muscle showed the largest expansions, modal allele lengths in skin were also very large and frequently exceeded 2000 CTG repeats. Similarly, the degree of somatic expansion in blood, muscle and skin were associated with each other. Notably, we found that the degree of somatic expansion in skin was highly predictive of that in skeletal muscle. More importantly, we established that individuals whose repeat expanded more rapidly than expected in one tissue (after correction for progenitor allele length and age) also expanded more rapidly than expected in other tissues. We also provide evidence suggesting that individuals in whom the repeat expanded more rapidly than expected in skeletal muscle have an earlier age at onset than expected (after correction for the progenitor allele length). Pyrosequencing analyses of the genomic DNA flanking the CTG repeat revealed that the degree of methylation in muscle was well predicted by the muscle modal allele length and age, but that neither methylation of the flanking DNA nor levels of DMPK sense and anti-sense transcripts could obviously explain individual- or tissue-specific patterns of somatic instability.
Assuntos
Distrofia Miotônica , Humanos , Distrofia Miotônica/genética , Expansão das Repetições de Trinucleotídeos/genética , Mucosa Bucal , Alelos , DNA/genética , Miotonina Proteína Quinase/genéticaRESUMO
Emerging respiratory viruses are major health threats due to their potential to cause massive outbreaks. Over the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has caused millions of cases of severe infection and deaths worldwide. Although natural and vaccine-induced protective immune mechanisms against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been increasingly identified, the factors that determine morbimortality are less clear. Comparing the immune signatures of COVID-19 and other severe respiratory infections such as the pandemic influenza might help dissipate current controversies about the origin of their severe manifestations. As such, identifying homologies in the immunopathology of both diseases could provide targets for immunotherapy directed to block shared pathogenic mechanisms. Meanwhile, finding unique characteristics that differentiate each infection could shed light on specific immune alterations exploitable for diagnostic and individualized therapeutics for each case. In this study, we summarize immunopathological aspects of COVID-19 and pandemic influenza from the perspective of cytokine storms as the driving force underlying morbidity. Thereby, we analyze similarities and differences in the cytokine profiles of both infections, aiming to bring forward those molecules more attractive for translational medicine and drug development.
Assuntos
COVID-19 , Influenza Humana , Síndrome da Liberação de Citocina , Humanos , Influenza Humana/epidemiologia , Influenza Humana/terapia , Pandemias , SARS-CoV-2RESUMO
Interferon-induced transmembrane (IFITM) proteins mediate protection against enveloped viruses by blocking membrane fusion at endosomes. IFITM1 and IFITM3 are crucial for protection against influenza, and various single nucleotide polymorphisms altering their function have been linked to disease susceptibility. However, bulk IFITM1 and IFITM3 mRNA expression dynamics and their correlation with clinical outcomes have not been extensively addressed in patients with respiratory infections. In this study, we evaluated the expression of IFITM1 and IFITM3 in peripheral leukocytes from healthy controls and individuals with severe pandemic influenza A(H1N1) or coronavirus disease 2019 (COVID-19). Comparisons between participants grouped according to their clinical characteristics, underlying disease, and outcomes showed that the downregulation of IFITM1 was a distinctive characteristic of severe pandemic influenza A(H1N1) that correlated with outcomes, including mortality. Conversely, increased IFITM3 expression was a common feature of severe pandemic influenza A(H1N1) and COVID-19. Using a high-dose murine model of infection, we confirmed not only the downregulation of IFITM1 but also of IFITM3 in the lungs of mice with severe influenza, as opposed to humans. Analyses in the comparative cohort also indicate the possible participation of IFITM3 in COVID-19. Our results add to the evidence supporting a protective function of IFITM proteins against viral respiratory infections in humans.
Assuntos
Antígenos de Diferenciação , COVID-19 , Influenza Humana , Proteínas de Membrana , Proteínas de Ligação a RNA , Animais , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , COVID-19/genética , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/genética , Leucócitos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
The costs of coronavirus disease 2019 (COVID-19) are devastating. With millions of deaths worldwide, specific serological biomarkers, antiviral agents, and novel therapies are urgently required to reduce the disease burden. For these purposes, a profound understanding of the pathobiology of COVID-19 is mandatory. Notably, the study of immunity against other respiratory infections has generated reference knowledge to comprehend the paradox of the COVID-19 pathogenesis. Past studies point to a complex interplay between cytokines and other factors mediating wound healing and extracellular matrix (ECM) remodeling that results in exacerbated inflammation, tissue injury, severe manifestations, and a sequela of respiratory infections. This review provides an overview of the immunological process elicited after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Also, we analyzed available data about the participation of matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-ß) in immune responses of the lungs. Furthermore, we discuss their possible implications in severe COVID-19 and sequela, including pulmonary fibrosis, and remark on the potential of these molecules as biomarkers for diagnosis, prognosis, and treatment of convalescent COVID-19 patients. Our review provides a theoretical framework for future research aimed to discover molecular hallmarks that, combined with clinical features, could serve as therapeutic targets and reliable biomarkers of the different clinical forms of COVID-19, including convalescence.
Assuntos
COVID-19 , Metaloproteinases da Matriz , Fator de Crescimento Transformador beta , Biomarcadores , COVID-19/imunologia , Efeitos Psicossociais da Doença , Humanos , Metaloproteinases da Matriz/imunologia , SARS-CoV-2 , Fator de Crescimento Transformador beta/imunologiaRESUMO
Resumen La neumonía sigue siendo una de las principales causas de consulta y de hospitalización a la que, además de su un alto impacto en términos de morbilidad y mortalidad, se suma la actual problemática de resistencia a los antimicrobianos, por lo que establecer directrices que permitan su adecuado diagnóstico y tratamiento es de gran importancia para obtener mejores desenlaces clínicos y promover un uso racional de antibióticos en estos pacientes. La presente guía de práctica clínica (GPC) contiene recomendaciones basadas en la evidencia para el diagnóstico y tratamiento de la neumonía adquirida en la comunidad en adultos, las cuales fueron realizadas mediante el proceso de adaptación de GPC basadas en la evidencia para el contexto colombiano.
Abstract Pneumonia continues to be one of the main causes of consultation and hospitalization to which, besides its high impact on morbidity and mortality, the current problem of antimicrobial resistance is added; thus, establishing guidelines that allow its adequate diagnosis and treatment is of great importance to obtain better clinical outcomes and promote a rational use of antibiotics in these patients. This clinical practice guideline (CPG) contains evidence-based recommendations for the diagnosis and treatment of community-acquired pneumonia in adult population; these recommendations were made by means of the process of adaptation of evidence-based CPGs for the Colombian context.
RESUMO
Resumen: ANTECEDENTES: El melanoma vaginal es una alteración excepcional, por lo que el diagnóstico se establece en etapas avanzadas de la enfermedad. El pronóstico a corto plazo es malo y no existen factores de riesgo identificados hasta la fecha. CASO CLINICO: Paciente de 77 años, acudió a consulta por sangrado transvaginal fétido, de dos meses de evolución. Durante la colposcopia se observó una tumoración en la cara lateral izquierda de la vagina, que se extendía hasta su tercio inferior; la cara anterior estaba hiperpigmentada y friable. De acuerdo con el reporte de citología y la biopsia se estableció el diagnóstico de melanoma invasor. La concentración de marcadores tumorales fue positiva para HMB-45, Ki-67 (20%), MART-1 (Melan-1) y PS-100. La paciente fue enviada al servicio de Oncología para estadificación y tratamiento de la enfermedad. CONCLUSIONES: La identificación de una tumoración hiperpigmentada en la exploración ginecológica, además de la biopsia dirigida complementada con estudio de inmunohistoquímica, es sugerente de melanoma vaginal. Las pacientes con este tipo de lesión deben atenderse por un equipo médico multidisciplinario.
Abstract: BACKGROUND: Vaginal melanoma is an exceptional alteration, for which the diagnosis is established in advanced stages of the disease. The short-term prognosis is poor and there are no identified risk factors to date. CLINICAL CASE: 77-year-old patient, who came to the clinic for fetid transvaginal bleeding, two months old. During colposcopy, a tumor was observed on the left lateral aspect of the vagina, which extended to its lower third; the anterior face was hyperpigmented and friable. Based on the cytology report and biopsy, the diagnosis of invasive melanoma was established. The concentration of tumor markers was positive for HMB-45, Ki 67 (20%), MART-1 (Melan-1) and PS-100. The patient was sent to the Oncology service for staging and treatment of the disease. CONCLUSIONS: The identification of a hyperpigmented tumor on gynecological examination, in addition to a directed biopsy, complemented by an immunohistochemical study, is suggestive of vaginal melanoma. Patients with this type of injury should be cared for by a multidisciplinary medical team.
RESUMO
Resumen Introducción . El entrenamiento nórdico ha sido estudiado para optimizar el gesto deportivo y prevenir lesiones en fútbol. Sin embargo, no se han reportado estudios que evidencien su efectividad sobre la fuerza explosiva del deporte. Objetivo. Determinar la efectividad de un protocolo de entrenamiento nórdico sobre la fuerza explosiva de miembros inferiores en futbolistas. Materiales y métodos. Se realizó un ensayo controlado y aleatorizado en el que 26 futbolistas masculinos fueron elegidos para hacer parte de un grupo intervención (n=12) y un grupo control (n=14). Al grupo intervención se le aplicó un protocolo de entrenamiento nórdico, mientras que el control realizó un programa de fortalecimiento convencional. Se evaluaron la fuerza explosiva de miembros inferiores, a través del Test de Bosco y Abalakov en una plataforma de salto, y el ángulo de mayor reclutamiento muscular del bíceps femoral durante la ejecución del ejercicio nórdico mediante de electromiografía de superficie. Resultados. Los dos grupos fueron homogéneos. Se evidenció una mejora en los componentes de la fuerza explosiva (p<0.05) para las variables de velocidad de despegue, de reclutamiento motor y de ángulo de registro del pico de reclutamiento motor en el grupo de intervención. Conclusión. La aplicación de un programa de entrenamiento en futbolistas demostró ser efectiva al influir de manera positiva en las variables involucradas en la fuerza explosiva.
Abstract Introduction: Nordic training has been designed to optimize the sporting movement and prevent injuries in soccer players. However, there are no reports on studies that demonstrate its effectiveness on the explosive power of such sport. Objective: To determine the effectiveness of a Nordic training protocol on the explosive force of lower limbs in soccer players. Materials and methods: A randomized controlled study was performed, in which 26 male players were chosen to be part of an intervention group (n=12) and a control group (n=14). The intervention group was applied a Nordic training protocol, while the control group followed a conventional strengthening program. The explosive force of lower limbs was evaluated through the Bosco and Abalakov tests on a jumping platform, as well as the angle of greater biceps femoris muscle recruitment while performing the Nordic exercise through surface electromyography. Results: Both groups were homogeneous. An improvement was evident in the components of the explosive force (p<0.05) for takeoff speed, the motor recruiting and the peak registration of angle recruitment variables in the intervention group. Conclusion: The implementation of a training program in soccer players proved to be effective by positively influencing the variables involved in the explosive force.
RESUMO
Cirurgias de revisão de artroplastias do quadril têm se tornado freqüentes. As complicações relacionadas seguem a mesma tendência. O objetivo é determinar a incorporação dos enxertos ósseos estruturais utilizados em revisão de artroplastia do quadril. Estudo retrospectivo com análise clínica e radiográfica de pacientes submetidos a revisão de artroplastia do quadril com uso de enxerto homólogo. Os enxertos foram coletados de doadores cadáveres por equipe especializada da própria instituição (INTO)
Assuntos
Humanos , Artroplastia de Quadril , Transplante Ósseo , OrtopediaAssuntos
Humanos , Exercício Físico , Condicionamento Físico Humano , População Rural , Chile , Promoção da SaúdeRESUMO
Enxerto Ósseo homólogo foi utilizado para reconstrução de defeitos ósseos na tíbia, no fêmur ou em ambos em artroplastias de revisão do joelho efetuadas no HTO-INTO entre os anos de 2000 e 2004