Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor ...prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl- d -lactosamine in T. cruzi –infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy.
Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available ...diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (
= 28), CD indeterminate form (
= 10) and healthy controls (
= 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.
It is observed that the number of onshore wind farms that reach the end of their service life is continually increasing. The decision-making process that defines the future of the farm is a challenge ...for the owners. This systematic review aimed to identify which factors influence the decision-making process at the end-of-life cycle of onshore wind farms. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, a research strategy was developed and used the Scopus, Web of Science and EMBASE databases. Initially, 2767 articles were identified, but, after double-blind screening, 26 articles were analyzed in full. The scarcity of studies on this topic and little elucidation are limitations of this review. The results include (i) a systematization of six options for decision making, (ii) thirteen factors influencing the decision-making process associated with categories of external factors (logistics and infrastructure aspects, regulatory aspects and public policies, national energy guidelines, the technological development of the sector); and internal factors (economic/financial, operational and environmental aspects). It is concluded that most of the publications consist of simulations and theoretical studies highlighting a bottleneck in experiences and feasible data to support decisions at the end of service life. It is highlighted that most of the studies showed that partial decommissioning with partial repowering, as well as total decommissioning, were the most feasible options for the end-of-life cycle, with aspects related to public policies and regulatory aspects, as well as environmental, operational and economic/financial aspects, being the most influential, especially due to the wake effect, operation and maintenance costs (OPEX) and the protection of guarantees and incentives for operation in a new operating cycle.
BACKGROUND
Soybean seed treatment with fungicides is a well‐established disease management strategy. However, the movement of these fungicides within seedlings is not always well characterized. Thus, ...the objectives of this study were to determine the pattern of translocation of three fungicides with different modes of action applied as a seed treatment, and the effect of soil type on translocation.
RESULTS
Most of the absorbed radioactivity was concentrated in the cotyledons and the maximum sum of the rates of absorption by roots, stems, and leaves of the plants was 15%. In most cases, absorption by roots, stems, and leaves were lower than 5% for 14C‐pyraclostrobin and 14C‐metalaxyl, and 1.6% for 14C‐carbendazim. Fungicides absorbed by the roots and the whole seedlings were higher when plants were grown in soil with lower organic matter content. Fungicides in the cotyledons are unlikely to be redistributed and are lost when cotyledons fall off the plants.
CONCLUSION
Cotyledons are the part of the plant where fungicides are most absorbed, regardless of the fungicide. Soil type affects the absorption of fungicides, and in this study it was most likely caused by soil organic matter. These data improve knowledge of the movement of seed treatment fungicides in soybean seedlings and may help the development of seed treatment chemistry to manage seed and soilborne pathogens.
Fungicide seed treatment is an important tool for disease management. This article shows that a small amount of fungicide is absorbed by the plants and soil type influences fungicide distribution.
Heart failure (HF) is one of the leading causes of hospitalization in adults in Brazil. However, most of the available data is limited to unicenter registries. The BREATHE registry is the first to ...include a large sample of hospitalized patients with decompensated HF from different regions in Brazil.
Describe the clinical characteristics, treatment and prognosis of hospitalized patients admitted with acute HF.
Observational registry study with longitudinal follow-up. The eligibility criteria included patients older than 18 years with a definitive diagnosis of HF, admitted to public or private hospitals. Assessed outcomes included the causes of decompensation, use of medications, care quality indicators, hemodynamic profile and intrahospital events.
A total of 1,263 patients (64±16 years, 60% women) were included from 51 centers from different regions in Brazil. The most common comorbidities were hypertension (70.8%), dyslipidemia (36.7%) and diabetes (34%). Around 40% of the patients had normal left ventricular systolic function and most were admitted with a wet-warm clinical-hemodynamic profile. Vasodilators and intravenous inotropes were used in less than 15% of the studied cohort. Care quality indicators based on hospital discharge recommendations were reached in less than 65% of the patients. Intrahospital mortality affected 12.6% of all patients included.
The BREATHE study demonstrated the high intrahospital mortality of patients admitted with acute HF in Brazil, in addition to the low rate of prescription of drugs based on evidence.
Background Cardiac arrhythmias are the main cause of sudden death due to Chronic Chagasic Cardiomyopathy (CCC). Here we investigated alterations in connexin 43 (Cx43) expression and phosphorylation ...in cardiomyocytes as well as associations with cardiac arrhythmias in CCC. Methods C57Bl/6 mice infected with Trypanosoma cruzi underwent cardiac evaluations at 6 and 12 months after infection via treadmill testing and EKG. Histopathology, cytokine gene expression, and distribution of total Cx43 and its phosphorylated forms Cx43 S368 and Cx43 S325/328/330 were investigated. Human heart samples obtained from subjects with CCC were submitted to immunofluorescence analysis. In vitro simulation of a pro-inflammatory microenvironment (IL-1β, TNF, and IFN-γ) was performed in H9c2 cells and iPSC-derived cardiomyocytes to evaluate Cx43 distribution, action potential duration, and Lucifer Yellow dye transfer. Results Mice chronically infected with T. cruzi exhibited impaired cardiac function associated with increased inflammation, fibrosis and upregulated IL-1β, TNF, and IFN-γ gene expression. Confocal microscopy revealed altered total Cx43, Cx43 S368 and Cx43 S325/328/330 localization and phosphorylation patterns in CCC, with dispersed staining outside the intercalated disc areas, i.e., in lateral membranes and the cytoplasm. Reduced co-localization of total Cx43 and N-cadherin was observed in the intercalated discs of CCC mouse hearts compared to controls. Similar results were obtained in human CCC heart samples, which showed Cx43 distribution outside the intercalated discs. Stimulation of human iPSC-derived cardiomyocytes or H9c2 cells with IL-1β, TNF, and IFN-γ induced alterations in Cx43 localization, reduced action potential duration and dye transfer between adjacent cells. Conclusion Heart inflammation in CCC affects the distribution and phosphorylation pattern of Cx43, which may contribute to the generation of conduction disturbances in Chagas disease.
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