[WITHDRAWN] Chagas Cardiomyopathy and Aerobic Exercise: a Systematic Review / [RETIRADO] CARDIOPATIA CHAGÁSICA E EXERCÍCIO FÍSICO AERÓBICO: uma revisão sistemática

A cardiomiopatia chagásica é uma consequência crônica da doença de Chagas e representa uma das principais causas de morbidade e mortalidade na América Latina. O exercício físico aeróbico tem sido reconhecido pelos seus benefícios à saúde cardiovascular. Portanto, o estudo tem como objetivo avaliar os efeitos do exercício físico aeróbico na função cardíaca, capacidade de exercício e qualidade de vida em pacientes com cardiomiopatia chagásica. Foi utilizado um referencial teórico-metodológico baseado na análise de estudos encontrados nas bases de dados PubMed, Scopus e Web of Science durante um período de cinco anos. Os resultados indicam que o exercício físico aeróbio pode ser uma estratégia terapêutica complementar eficaz, contribuindo para a melhoria da função cardíaca, aumento da capacidade de exercício e melhoria da qualidade de vida dos pacientes. No entanto, é importante destacar a necessidade de mais estudos para padronizar os protocolos de exercício e identificar os mecanismos específicos pelos quais o exercício beneficia os pacientes com cardiomiopatia chagásica. Conclui-se que, apesar das limitações existentes, a prática de exercício físico aeróbico apresenta potencial significativo para reabilitação cardíaca em indivíduos acometidos pela doença de Chagas e deve ser considerada como parte do plano de tratamento.

A cardiopatia chagásica é uma consequência crônica da doença de Chagas e representa uma das principais causas de morbimortalidade na América Latina. O exercício físico aeróbico tem sido reconhecido por seus benefícios à saúde cardiovascular. Assim, o estudo tem como objetivo avaliar os efeitos do exercício físico aeróbico na função cardíaca, na capacidade de exercício e na qualidade de vida de pacientes com cardiopatia chagásica. Utilizou-se um referencial teórico-metodológico baseado na análise de estudos encontrados nas bases de dados PubMed, Scopus e Web of Science, em sete anos. Os resultados indicam que o exercício físico aeróbico pode ser uma estratégia terapêutica complementar eficaz, contribuindo para a melhoria da função cardíaca, aumento da capacidade de exercício e melhoria da qualidade de vida dos pacientes. No entanto, destaca-se a necessidade de mais estudos para padronizar protocolos de exercício e identificar os mecanismos específicos pelos quais o exercício beneficia pacientes com cardiopatia chagásica. Conclui-se que, apesar das limitações existentes, a prática de exercício físico aeróbico apresenta um potencial significativo para a reabilitação cardíaca em indivíduos acometidos pela doença de Chagas, devendo ser considerada como parte do plano de tratamento.

The Prevalence of Metallo-Beta-Lactamese-(MßL)-Producing Pseudomonas aeruginosa Isolates in Brazil: A Systematic Review and Meta-Analysis.

The purpose of the current study is to describe the prevalence of Pseudomonas aeruginosa (PA)-producing MßL among Brazilian isolates and the frequency of blaSPM-1 in MßL-PA-producing isolates. From January 2009 to August 2023, we carried out an investigation on this subject in the internet databases SciELO, PubMed, Science Direct, and LILACS. A total of 20 papers that met the eligibility requirements were chosen by comprehensive meta-analysis software v2.2 for data retrieval and analysis by one meta-analysis using a fixed-effects model for the two investigations. The prevalence of MßL-producing P. aeruginosa was 35.8% or 0.358 (95% CI = 0.324-0.393). The studies' differences were significantly different from one another (x2 = 243.15; p < 0.001; I2 = 92.18%), so they were divided into subgroups based on Brazilian regions. There was indication of asymmetry in the meta-analyses' publishing bias funnel plot; so, a meta-regression was conducted by the study's publication year. According to the findings of Begg's test, no discernible publishing bias was found. blaSPM-1 prevalence was estimated at 66.9% or 0.669 in MßL-PA isolates (95% CI = 0.593-0.738). The analysis of this one showed an average heterogeneity (x2 = 90.93; p < 0.001; I2 = 80.20%). According to the results of Begg's test and a funnel plot, no discernible publishing bias was found. The research showed that MßL-P. aeruginosa and SPM-1 isolates were relatively common among individuals in Brazil. P. aeruginosa and other opportunistic bacteria are spreading quickly and causing severe infections, so efforts are needed to pinpoint risk factors, reservoirs, transmission pathways, and the origin of infection.

Evaluation of the Hematological Patterns from Up to 985 Days of Long COVID: A Cross-Sectional Study.

Long COVID affects many individuals following acute coronavirus disease 2019 (COVID-19), and hematological changes can persist after the acute COVID-19 phase. This study aimed to evaluate these hematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a 'long COVID' clinical care program in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected to quantify erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalized in the acute phase had higher mean red/white blood cell, platelet, and plateletcrit levels and red blood cell distribution width. Furthermore, hematimetric parameters were higher in shorter periods of long COVID than in longer periods. Patients with more than six concomitant long COVID symptoms had a higher white blood cell count, a shorter prothrombin time (PT), and increased PT activity. Our results indicate there may be a compensatory mechanism for erythrogram-related markers within 985 days of long COVID. Increased levels of leukogram-related markers and coagulation activity were observed in the worst long COVID groups, indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.

Metabolic Profile of Patients with Long COVID: A Cross-Sectional Study.

A significant proportion of patients experience a wide range of symptoms following acute coronavirus disease 2019 (COVID-19). Laboratory analyses of long COVID have demonstrated imbalances in metabolic parameters, suggesting that it is one of the many outcomes induced by long COVID. Therefore, this study aimed to illustrate the clinical and laboratory markers related to the course of the disease in patients with long COVID. Participants were selected using a clinical care programme for long COVID in the Amazon region. Clinical and sociodemographic data and glycaemic, lipid, and inflammatory screening markers were collected, and cross-sectionally analysed between the long COVID-19 outcome groups. Of the 215 participants, most were female and not elderly, and 78 were hospitalised during the acute COVID-19 phase. The main long COVID symptoms reported were fatigue, dyspnoea, and muscle weakness. Our main findings show that abnormal metabolic profiles (such as high body mass index measurement and high triglyceride, glycated haemoglobin A1c, and ferritin levels) are more prevalent in worse long COVID presentations (such as previous hospitalisation and more long-term symptoms). This prevalence may suggest a propensity for patients with long COVID to present abnormalities in the markers involved in cardiometabolic health.

Análise da tendência espaço-temporal da hepatite B no estado do Pará, 2006 a 2018 / Analysis of the Spatio-temporal trend of hepatitis B in the state of Pará, 2006 to 2018

Objetivo: o presente estudo tem por objetivo realizar uma análise do perfil espaço-temporal da hepatite B no estado do Pará, entre os anos de 2006 e 2018. Métodos: trata-se de um trabalho epidemiológico, ecológico e descritivo, realizado no estado do Pará por meio de seus municípios e regiões de saúde. A base de dados foi levantada perante consulta ao Departamento de Informática do SUS (DATASUS). Foram calculadas as variações percentuais anuais (APC) nas taxas de incidência de hepatite B, mediante a modelagem pelo método Jointpoint, usando o ano calendário como variável de regressão. Resultados: no estado do Pará, foram notificados, no período do estudo, 3,228 casos, sendo, 48,3% em homens e 51,7% em mulheres, com média de 248,3 casos por ano (61,8 de desvio padrão). A taxa de incidência média entre os anos de 2006 a 2018, nos 144 municípios no estado do Pará, obteve uma grande variação de 0 a 21,54 casos por 100.000 mil habitantes. Conclusão: apesar da dispersão nas taxas de incidência, obteve-se uma tendência crescente da ocorrência de casos de hepatite B no período estudado, sugerindo a necessidade de medidas de saúde pública mais eficazes no combate ao HBV.

Objective: this study aims to analyze the spatiotemporal profile of hepatitis B in the State of Pará from 2006 to 2018. Methods: this is an ecological and descriptive epidemiological study carried out in the State of Pará through its municipalities and health regions. The database was collected from the consultation with the SUS Computer Department (DATASUS). The annual percentage changes (APC) in the hepatitis B incidence rates were calculated through modeling by the Jointpoint method, using the calendar year as a regressive variable. Results: in the state of Pará, 3,228 cases were reported, of which 48.3% were men and 51.7% were women, with an average of 248.3 cases per year (61.8 standard deviations). The average incidence rate between the years 2006 to 2018 in the 144 municipalities in the state of Pará obtained a wide variation from 0 to 21.54 cases per 100,000 inhabitants. Conclusions: despite the dispersion in incidence rates, there was an incre

Human pegivirus (HPgV, GBV-C) RNA in volunteer blood donors from a public hemotherapy service in Northern Brazil.

BACKGROUND: Human pegivirus (HPgV)-formerly known as GBV-C-is a member of the Flaviviridae family and belongs to the species Pegivirus C. It is a non-pathogenic virus and is transmitted among humans mainly through the exposure to contaminated blood and is often associated with human immunodeficiency virus (HIV) infection, among other viruses. This study aimed to determine the prevalence of HPgV viremia, its association with HIV and clinical epidemiological factors, as well as the full-length sequencing and genome characterization of HPgV recovered from blood donors of the HEMOPA Foundation in Belém-PA-Brazil. METHODS: Plasma samples were obtained from 459 donors, tested for the presence of HPgV RNA by the RT-qPCR. From these, a total of 26 RT-qPCR positive samples were submitted to the NGS sequencing approach in order to obtain the full genome. Genome characterization and phylogenetic analysis were conducted. RESULTS: The prevalence of HPgV was 12.42%. We observed the highest prevalences among donors aged between 18 and 30 years old (16.5%), with brown skin color (13.2%) and men (15.8%). The newly diagnosed HIV-1 prevalence was 26.67%. The HPgV genotype 2 (2a and 2b) was identified. No data on viral load value was found to corroborate the protective effect of HPgV on HIV evolution. CONCLUSIONS: This study provided information regarding the HPgV infection among blood donors from HEMOPA Foundation. Furthermore, we genetically characterized the HPgV circulating strains and described by the first time nearly complete genomes of genotype 2 in Brazilian Amazon.

Epidemiological and TNFα polymorphism evaluation in patients with cryptococcal meningitis treated at a referral hospital in North Brazil.

INTRODUCTION: The present study evaluated the epidemiology of cryptococcal meningitis and TNFα gene polymorphisms in patients at a reference hospital in northern Brazil. METHODS: Samples from 25 patients infected with Cryptococcus spp. were collected to confirm the infection and to analyze the TNFα gene polymorphisms. RESULTS: Cryptococcus neoformans was detected as the predominant etiological agent (100%) in HIV-positive patients. No genetic polymorphic changes were found. CONCLUSIONS: No correlation was observed between the analyzed TNFα polymorphisms and cryptococcal meningitis.

Epidemiological and TNFα polymorphism evaluation in patients with cryptococcal meningitis treated at a referral hospital in North Brazil

Abstract INTRODUCTION: The present study evaluated the epidemiology of cryptococcal meningitis and TNFα gene polymorphisms in patients at a reference hospital in northern Brazil. METHODS: Samples from 25 patients infected with Cryptococcus spp. were collected to confirm the infection and to analyze the TNFα gene polymorphisms. RESULTS: Cryptococcus neoformans was detected as the predominant etiological agent (100%) in HIV-positive patients. No genetic polymorphic changes were found. CONCLUSIONS: No correlation was observed between the analyzed TNFα polymorphisms and cryptococcal meningitis.

Mortality in patients with multidrug-resistant Pseudomonas aeruginosa infections: a meta-analysis.

Pseudomonas aeruginosa is the leading cause of nosocomial infections with high mortality rates owing to the limited therapeutic options for multidrug-resistant Pseudomonas aeruginosa (MDRPA) and metallo-beta-lactamase (MBL)-producing strains. Herein, we present a meta-analysis exploring the association between MDRPA and São Paulo MBL-1 (SPM-1)-producing strains vs. mortality. Online databases were screened to identify studies published between 2006 and 2016. A total of 15 studies, comprising 3,201 cases of P. aeruginosa infection, were included. Our results demonstrated a higher mortality rate among patients infected with MDRPA (44.6%, 363/813) than those with non-MDRPA infection (24.8%, 593/2,388) [odds ratio (OR) 2.39, 95% confidence interval (CI) 1.70-3.36, p <0.00001]. The risk of mortality in patients with non-SPM-1 strains was four times higher than that observed in the patients of the SPM-1 group; however, no statistically significant difference was observed (p = 0.43). In conclusion, the results of our study demonstrated that patients infected with MDRPA had a significantly higher mortality rate than that of patients infected with non-MDRPA strains, especially patients with bloodstream infection (BSI), immunosuppression, and inadequate antimicrobial therapy. The absence of studies on the molecular aspects of blaSPM-1 and its association with mortality limited the analysis; therefore, our results should be interpreted with caution. Our findings also highlight the need for more studies on the molecular aspects of resistance and the peculiarities of different nosocomial settings.

Mortality in patients with multidrug-resistant Pseudomonas aeruginosa infections: a meta-analysis

Abstract Pseudomonas aeruginosa is the leading cause of nosocomial infections with high mortality rates owing to the limited therapeutic options for multidrug-resistant Pseudomonas aeruginosa (MDRPA) and metallo-beta-lactamase (MBL)-producing strains. Herein, we present a meta-analysis exploring the association between MDRPA and São Paulo MBL-1 (SPM-1)-producing strains vs. mortality. Online databases were screened to identify studies published between 2006 and 2016. A total of 15 studies, comprising 3,201 cases of P. aeruginosa infection, were included. Our results demonstrated a higher mortality rate among patients infected with MDRPA (44.6%, 363/813) than those with non-MDRPA infection (24.8%, 593/2,388) [odds ratio (OR) 2.39, 95% confidence interval (CI) 1.70-3.36, p <0.00001]. The risk of mortality in patients with non-SPM-1 strains was four times higher than that observed in the patients of the SPM-1 group; however, no statistically significant difference was observed (p = 0.43). In conclusion, the results of our study demonstrated that patients infected with MDRPA had a significantly higher mortality rate than that of patients infected with non-MDRPA strains, especially patients with bloodstream infection (BSI), immunosuppression, and inadequate antimicrobial therapy. The absence of studies on the molecular aspects of blaSPM-1 and its association with mortality limited the analysis; therefore, our results should be interpreted with caution. Our findings also highlight the need for more studies on the molecular aspects of resistance and the peculiarities of different nosocomial settings.

Organic effects of associating paclitaxel with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella.

Lipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m2) and three with higher (250 mg/m2) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses. In the LDE-PTX group, no clinical toxicity appeared, and the weight-food consumption curve was similar to that of the controls. Two animals treated with commercial PTX presented weight loss, nausea and vomiting, diarrhea, skin flaking, 70% loss of body hair, and decreased physical activity. The use of LDE as a carrier at both lower and higher doses reduced the toxicity of the drug in this species, which is closely related to human subjects. This was observed not only by clinical, biochemical, and hematological profiles but also by the histopathological analysis. The results of this study support the assumption that lipid-based nanoparticle systems used as drug carriers can serve as valuable tools to decrease the toxicity and increase the safety of chemotherapeutic agents.

Evaluation of the immunological cellular response of Cebus apella exposed to the carcinogen N-methyl-N-nitrosourea and treated with CANOVA®.

The immune response modifier Canova® is a homeopathic remedy indicated for patients with depressed immune system, since this drug appears to increase adaptive immunity and induce an immune response against multiple and severe pathological conditions, including cancer. We evaluated the pattern of immune cellular response in non-human primates of the species Cebus apella exposed to N-methyl-N-nitrosourea (MNU) with and without Canova®. Twelve animals were divided into four groups, with three animals each: negative control and three experimental groups, MNU-alone (35 days); MNU (35 days)-plus-Canova® (3 days) and Canova®-alone (3 days). The animals received MNU orally and Canova® by three intravenous injections. Evaluation of the cellular immune response was performed by immunophenotyping of T-lymphocytes (CD4(+), CD8(+)), B-lymphocytes and natural killer cells. Analysis was also performed of the cell cycle. Our results suggest an increase of T-lymphocytes (CD4(+)CD3(+)) only in the Canova® group, while in the MNU-plus-Canova® group only B-lymphocytes increased.

Chromosome X aneuploidy in Brazilian schizophrenic patients.

The identification of cytogenetic abnormalities in schizophrenic patients may provide clues to the genes involved in this disease. For this reason, a chromosomal analysis of samples from 62 schizophrenics and 70 controls was performed with trypsin-Giemsa banding and fluorescence in situ hybridization of the X chromosome. A clonal pericentric inversion on chromosome 9 was detected in one male patient, and we also discovered mosaicism associated with X chromosome aneuploidy in female patients, primarily detected in schizophrenic and normal female controls over 40 years old. When compared with age-matched female controls, the frequency of X chromosome loss was not significantly different between schizophrenics and controls, except for the 40- to 49-year-old age group. Our findings suggest that the X chromosome loss seen in schizophrenic patients is inherent to the normal cellular aging process. However, our data also suggest that X chromosome gain may be correlated with schizophrenia in this Brazilian population.

Lymphocyte proliferation stimulated by activated human macrophages treated with Canova.

INTRODUCTION: Canova (CA) is a homeopathic medication with immunomodulatory properties, recommended for patients with a depressed immune system. CA has been reported to increase in leukocyte numbers, cellular differentiation and reduction in tumor size. AIM AND METHOD: Since CA may stimulate lymphocyte differentiation, proliferation, and/or survival, the aim of the present study was to compare the mitotic index (MI) of phytohemagglutinin-stimulated human lymphocytes cultured in a medium supplemented with human macrophages activated by CA, with lymphocytes cultured in a medium without CA-treated macrophages. RESULTS: In this study, the MI of lymphocyte cultured received the medium containing CA-stimulated macrophages showed a higher proliferation index (p<0.01) than the lymphocytes cultured in a medium without CA-treated macrophages. Our results suggest that CA treatment, in addition to activating macrophages, indirectly induces lymphocyte proliferation and has potential as a new adjuvant therapeutic approach.

Genotoxic effects of white fluorescent light on human lymphocytes in vitro.

Sources of light beams such as white fluorescent light, are present in our daily life to meet the needs of life in the modern world. This study was conducted with the objective of determining the possible genotoxic, cytotoxic and aneugenic effects caused by this agent in different stages of the cell cycle (G0/early G1, S, and late G2), using different cytogenetic parameters (sister chromatid exchanges--SCE, chromosome aberrations--CA, and detection of aneugenic effects) in lymphocytes from temporary cultures of human peripheral blood. WFL showed a genotoxic effect in vitro, expressed by an increase in the frequency of SCE's, regardless of the cell cycle stage. However, no increase in the frequency of CAs was observed. In addition, disturbances in cell cycle kinetics and chromosomal segregation were also observed. Taken together, such data may contribute to a better understanding and a different management in the use of phototherapy for some pathological conditions.

Genotoxic effects of rotenone on cultured lymphocytes.

Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.

Mutagenicity of hydroxyurea in lymphocytes from patients with sickle cell disease

Hydroxyurea is commonly used in the treatment of myeloproliferative diseases and in patients with sickle cell disease (SCD). The use of this antineoplastic agent in patients with SCD is justified because of the drug's ability to increase fetal hemoglobin levels, thereby decreasing the severity of SCD. However, high doses or prolonged treatment with hydroxyurea can be cytotoxic or genotoxic for these patients, with an increased risk of developing acute leukemia. This danger can be avoided by monitoring the lymphocytes of patients treated with hydroxyurea. Cytogenetic tests are important endpoints for monitoring the physiological effects of physical and chemical agents, including drugs. In this work, we assessed the genotoxicity of hydroxyurea in short-term cultures of lymphocytes from SCD patients. Hydroxyurea was not cytotoxic or genotoxic at the concentrations tested in the G2 phase of the cell cycle. These results support the use of hydroxyurea in the treatment of SCD, although further work is necessary to understand the effects of this drug in vivo.

Evaluation of the mutagenic activity of hydroxyurea on the G1-S-G2 phases of the cell cycle: an in vitro study.

Hydroxyurea is considered an antineoplastic drug, which also plays an important role in the treatment of sickle cell anemia patients. We evaluated and compared the clastogenic and cytotoxic effects of hydroxyurea, using chromosomal aberrations and mitotic index, respectively, as endpoints. In vitro short-term cultures of lymphocytes were exposed to several concentrations of this drug, at various cell cycle phases. There was a significant increase in the cytotoxicity of hydroxyurea at G1 and G1/S as well in the G2 phase of the cell cycle. Hydroxyurea did not significantly increase chromosome aberrations. There was an S-dependent cytotoxic effect of hydroxyurea, which is expected based on the known activity of hydroxyurea as an inhibitor of ribonucleotide reductase.