TGF-β involvement in Chagas disease cardiomyopathy has been clearly demonstrated. The TGF-β signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an ...increase in extracellular matrix protein expression. The aim of this study was to investigate the effect of GW788388, a selective inhibitor of TβR1/ALK5, on cardiac function in an experimental model of chronic Chagas' heart disease. To this end, C57BL/6 mice were infected with Trypanosoma cruzi (102 parasites from the Colombian strain) and treated orally with 3mg/kg GW788388 starting at 120 days post-infection (dpi), when 100% of the infected mice show cardiac damage, and following three distinct treatment schedules: i) single dose; ii) one dose per week; or iii) three doses per week during 30 days. The treatment with GW788388 improved several cardiac parameters: reduced the prolonged PR and QTc intervals, increased heart rate, and reversed sinus arrhythmia, and atrial and atrioventricular conduction disorders. At 180 dpi, 30 days after treatment interruption, the GW3x-treated group remained in a better cardiac functional condition. Further, GW788388 treatment reversed the loss of connexin-43 enriched intercellular plaques and reduced fibrosis of the cardiac tissue. Inhibition of the TGF-β signaling pathway reduced TGF-β/pSmad2/3, increased MMP-9 and Sca-1, reduced TIMP-1/TIMP-2/TIMP-4, and partially restored GATA-6 and Tbox-5 transcription, supporting cardiac recovery. Moreover, GW788388 administration did not modify cardiac parasite load during the infection but reduced the migration of CD3+ cells to the heart tissue. Altogether, our data suggested that the single dose schedule was not as effective as the others and treatment three times per week during 30 days seems to be the most effective strategy. The therapeutic effects of GW788388 are promising and suggest a new possibility to treat cardiac fibrosis in the chronic phase of Chagas' heart disease by TGF-β inhibitors.
Chronic Chagasic cardiomyopathy (CCC), a progressive inflammatory and fibrosing disease, is the most prominent clinical form of Chagas disease, a neglected tropical disease caused by
infection. ...During CCC, the parasite remains inside the cardiac cells, leading to tissue damage, involving extensive inflammatory response and irregular fibrosis. Among the fibrogenic factors is transforming growth factor-β (TGF-β), a key cytokine controlling extracellular matrix synthesis and degradation. TGF-β is involved in CCC onset and progression, with increased serum levels and activation of its signaling pathways in the cardiac tissue, which crucially contributes to fibrosis. Inhibition of the TGF-β signaling pathway attenuates
infection and prevents cardiac damage in an experimental model of acute Chagas disease. The aim of this study was to investigate the effect of TGF-β neutralization on
infection in both
and
pre-clinical models, using the 1D11 monoclonal antibody. To this end, primary cultures of cardiac cells were infected with
trypomastigote forms and treated with 1D11. For
studies, 1D11 was administered in different schemes for acute and chronic phase models (Swiss mice infected with 10
parasites from the Y strain and C57BL/6 mice infected with 10
parasites from the Colombian strain, respectively). Here we show that the addition of 1D11 to cardiac cells greatly reduces cardiomyocyte invasion by
and the number of parasites per infected cell. In both acute and chronic experimental models,
infection altered the electrical conduction, decreasing the heart rate, increasing the PR interval and the P wave duration. The treatment with 1D11 reduced cardiac fibrosis and reversed electrical abnormalities improving cardiac performance. Taken together, these data further support the major role of the TGF-β signaling pathways in
-infection and their biological consequences on parasite/host interactions. The therapeutic effects of the 1D11 antibody are promising and suggest a new possibility to treat cardiac fibrosis in the chronic phase of Chagas' heart disease by TGF-β neutralization.
Resumo A pandemia causada pelo novo coronavírus (SARS-CoV-2) configura quadro de emergência de saúde pública mundial. Algumas categorias ocupacionais têm risco elevado de exposição à infecção, como ...os(as) trabalhadores(as) da saúde. Neste artigo, objetiva-se sumarizar e sistematizar aspectos relativos às condições de trabalho e de saúde dos(as) trabalhadores(as) da saúde nessa pandemia, enfatizando a situação no Brasil, experiências exitosas na proteção do trabalho em saúde em outros países e recomendações para o contexto brasileiro. Iniciativas imediatas de proteção e combate à pandemia em outros países incluíram como pontos estratégicos: adequação das condições de trabalho; testagem sistemática e ações específicas de assistência aos(às) trabalhadores(as). Para o enfrentamento da Covid-19 no Brasil, destacam-se como recomendações: revisão de fluxos de atendimento e definição de características e condições para cada etapa de atendimento; estabelecimento da Covid-19 como doença relacionada ao trabalho para os grupos expostos; registro efetivo da ‘ocupação’ nos sistemas de informação; estabelecimento de condições especiais para execução do trabalho na situação de epidemia; atenção às jornadas laborais e ações para redução de estressores ocupacionais. A atuação desses(as) trabalhadores(as) é elemento central no enfrentamento da pandemia, portanto, o plano de combate ao Covid-19 deve incluir proteção e preservação de sua saúde física e mental.
Abstract The pandemic caused by the new coronavirus (SARS-CoV-2) is a worldwide public health emergency. Some occupational categories, such as health workers, are at high risk of exposure to the infection. This article aims to summarize and systematize aspects related to the health and working conditions of health workers in this pandemic, especially in Brazil, successful experiences in the protection of healthcare work in other countries and recommendations for the Brazilian context. Immediate initiatives to protect and combat the pandemic in other countries included as strategic points: adequacy of working conditions; systematic testing and specific assistance actions for healthcare workers. In order to face COVID-19 in Brazil, the following recommendations stand out: review of service flows and definition of characteristics and conditions for each stage of service; establishment of COVID-19 as a work-related disease for exposed groups; effective registration of ‘occupation’ in information systems; establishment of special conditions for carrying out work in the event of an epidemic; attention to working hours and actions to reduce occupational stressors. The performance of these workers is a central element in facing the pandemic, therefore, the plan to combat COVID-19 must include protection and preservation of their physical and mental health.
Resumen La pandemia causada por el nuevo coronavirus (SARS-CoV-2) constituye una emergencia mundial de la salud pública. Algunas categorías profesionales corren un alto riesgo de exposición a la infección, como lo son los trabajadores de la salud. Este artículo tiene como objetivo resumir y sistematizar aspectos relacionados a las condiciones laborales y de salud de los trabajadores de salud en esta pandemia, enfatizando la situación en Brasil, experiencias que dieron resultado para la protección del trabajo de salud en otros países y recomendaciones para el contexto brasileño. Iniciativas inmediatas de protección y combate de la pandemia en otros países incluyen como puntos estratégicos: adecuación de las condiciones de trabajo; pruebas sistemáticas y acciones puntuales de asistencia para los trabajadores. Para enfrentar el COVID-19 en Brasil, se destacan las siguientes recomendaciones: revisión de los flujos de atendimiento y definición de características y condiciones para cada etapa del atendimiento; establecimiento de COVID-19 como enfermedad relacionada al trabajo para grupos expuestos; registro efectivo de “ocupación” en los sistemas de información; establecimiento de condiciones especiales para realizar trabajos en caso de epidemia; control de las horas de trabajo y acciones para reducir los motivadores de estrés laboral. El desempeño de estos trabajadores es un elemento central para enfrentar la pandemia, por lo tanto, el plan para combatir COVID-19 debe incluir protección y preservación de su salud física y mental.
CD8 T cells are regarded as pivotal players in both immunoprotection and immunopathology following Trypanosoma cruzi infection. Previously, we demonstrated the expansion of CD8+ T lymphocytes in the ...spleen of T. cruzi-infected mice under treatment with benznidazole (N-benzyl-2-nitroimidazole acetamide; Bz), a drug available for clinical therapy. This finding underlies the concept that the beneficial effects of Bz on controlling acute T. cruzi infection are related to a synergistic process between intrinsic trypanocidal effect and indirect triggering of the active immune response. In the present study, we particularly investigated the effect of Bz treatment on the CD8+ T cell subset following T. cruzi infection. Herein we demonstrated that, during acute T. cruzi infection, Bz treatment reduces and abbreviates the parasitemia, but maintains elevated expansion of CD8+ T cells. Within this subset, a remarkable group of CD8low cells was found in both Bz-treated and non-treated infected mice. In Bz-treated mice, early pathogen control paralleled the lower frequency of recently activated CD8low cells, as ascertained by CD69 expression. However, the CD8low subset sustains significant levels of CD44highCD62Llow and CD62LlowT-bethigh effector memory T cells, in both Bz-treated and non-treated infected mice. These CD8low cells also comprise the main group of spontaneous interferon (IFN)-γ-producing CD8+ T cells. Interestingly, following in vitro anti-CD3/CD28 stimulation, CD8+ T cells from Bz-treated T. cruzi-infected mice exhibited higher frequency of IFN-γ+ cells, which bear mostly a CD8low phenotype. Altogether, our results point to the marked presence of CD8low T cells that arise during acute T. cruzi infection, with Bz treatment promoting their significant expansion along with a potential effector program for high IFN-γ production.
Pulmonary tuberculosis is an indolent disease that may rarely be fatal. Extensive destruction of pulmonary parenchyma is rarely seen nowadays. This image shows a large tuberculosis cavitation that ...mimics massive a pneumothorax.
Transforming growth factor beta (TGF-β) is deeply involved on the pathogenesis of Chagas disease. Our group has been investigating the participation of this pleiotropic cytokine in different aspects ...of Chagas disease over the last 20 years. Important observations have been made, such as: (i) the ability of Trypanosoma cruzi in activating latent TGF-β; (ii) the potential involvement of TGF-β pathway on T. cruzi invasion of host cells; (iii) association of TGF-β with parasite intracellular replication; (iv) cardiac fibrosis development and maintenance; (v) disruption of Connexin-43 plaque structures and (vi) inflammation and immune response. In this perspective article we intend to discuss the advances of the potential use of new therapies targeting TGF-β to treat the cardiac alterations of Chagas disease-affected patients.
The analysis of sociodemographic and emotional factors is essential to understanding how men perceive stress and practice self-compassion. In health crises, this problem becomes an emergency for ...public health. This study aimed to analyze the influence of sociodemographic and emotional factors on the relationship between self-compassion and the perceived stress of men residing in Brazil during the COVID-19 pandemic. This is a nationwide cross-sectional study carried out between June and December 2020 with 1006 men who completed a semi-structured electronic questionnaire. Data were collected using the snowball technique. Perceived stress was measured by the Perceived Stress Scale (PSS-14), and self-compassion was assessed using the Self-Compassion Scale. Most men had low self-compassion (51.5%; n = 516) and a moderate level of perceived stress (60.9%; n = 613), while 15.9% (n = 170) had a high level of stress. The prevalence of men in the combined situation of low self-compassion and high perceived stress was 39.4% (n = 334). Living with friends had a higher prevalence of low self-compassion and high perceived stress. The prevalence of common mental disorders was high (54.3%). Men with low levels of self-compassion reported higher levels of perceived stress; however, this association was moderated by emotional and sociodemographic variables. These findings highlight the importance of considering individual and contextual factors in public policies promoting men’s mental health.
Translational research (TR) is an interdisciplinary branch of the biomedical field that seeks to connect its three supporting pillars: basic research on the bench, the hospital beds and other health ...system services, and the delivery of products for the well-being and health of the community. Here, we review the five transition stages of the TR spectrum, registering the lessons learned during > 20 years leading to the first clinical trial designed and performed in Brazil for testing a complementary treatment for Chagas disease (CD): the selenium trial (STCC). Lessons learned were: (1) to consider all the TR spectrum since the beginning of the project; (2) to start simultaneously animal studies and translation to humans; (3) to ensure a harmonious interaction between clinical and basic research teams; (4) to include MSc and PhD students only in pre-clinical and basic studies (TR0) or vertical clinical studies using retrospective samples and data (TR1); (5) to identify potential suppliers in the national commercial market for a future final treatment since the pre-clinical stage; (6) to keep an international network of experts as permanent advisers on the project. In the whole process, some perspectives were created: a complementary clinical trial for the opened questions and the construction of a Brazilian clinical CD platform.
This study aimed at identifying the perceptions of Brazilian postgraduate students from all over the country on the impacts of the COVID-19 pandemic on their academic trajectories. Data from 5985 ...postgraduate students were collected in the end of 2020, through a 37-item questionnaire, including multiple-choice questions, through Google Forms. The questions were divided into blocks with different proposals: personal profile, academic profile, issues related to COVID-19 infection, and issues related to mental health. Our analysis showed that 51.43% were master's degree students; 43.02% were doctorate and 5.55% were specialization students, mostly attending Biological, Health, and Human Sciences post-graduation courses (18.13%, 17.91%, and 17.38%, respectively) of different Brazilian educational institutions, including public (e.g., UFRJ) and private (e.g., PUC) federal universities as well as research institutions (e.g., Fiocruz) from all five regions of Brazil (north, south, southeast, northeast, and center Midwest). Most of them were academically impacted by the COVID-19 pandemic, which also involved psychological aspects such as high levels of anxiety and depression. The results showed readjustments of research projects, and academic activities, which in some particular research fields led to the successful completion through the remote activities. However, efforts are still needed by graduate programs in order to allow greater flexibility in academic activities to fulfill all previous planning and chronograms, in addition to implementing ongoing projects to support students' mental health.
Abstract Introduction: Abdominal aortic aneurysm is a prevalent disease in western world, with a high mortality rate when rupture occurs. Screening programs and elective surgery may prevent such a ...life-threatening event. We pretend to evaluate if internal medicine residents would be able to perform quality abdominal ultrasound for abdominal aortic aneurysm screening, and therefore increase our diagnostic accuracy of this life-threatening condition. Material and Methods: Five internal medicine residents without previous experience in ultrasound screened men over 65 years admitted to Internal Medicine wards for Abdominal Aortic Aneurysm. The patients were evaluated in different times by two internal medicine residents, and a subset of patients was also evaluated by vascular surgery attendant or abdominal computed tomography scan (established as gold standard evaluations). Agreement between both internal medicine resident’s observations and internal medicine residents’ and gold standard evaluations were analyzed. Results: A total of 98 patients were evaluated, with 8 abdominal aortic aneurysms diagnosed, resulting in an 8.2% prevalence. There was good agreement regarding Abdominal Aortic Aneurysm presence and measurement between internal medicine residents’ examinations (κ = 0.918, p < 0.01) and internal medicine residents’/gold standard (κ = 0.950, p < 0.01). Discussion and Conclusion: Abdominal aortic aneurysm prevalence in our study was high. Internal medicine residents were able to accurately diagnose aortic abdominal aneurysm. Point of care opportunistic aortic abdominal aneurysm screening can be performed in Internal Medicine wards, providing an early diagnosis and referral for elective repair surgery.
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