https://repositorio.ufu.br/handle/123456789/5488 2026-04-18T06:39:31Z https://repositorio.ufu.br/handle/123456789/48402 Title: Infecções relacionadas à assistência à saúde em unidades de terapia intensiva de adultos no Brasil: Uma abordagem multicêntrica Abstract: Healthcare-associated infections (HAIs) remain one of the major global health challenges, particularly in low- and middle-income countries such as Brazil, where the clinical and economic impact is exacerbated by the high prevalence of multidrug-resistant microorganisms. This thesis, composed of three interrelated articles, integrates different aspects of the epidemiology and dissemination of Klebsiella pneumoniae and Acinetobacter baumannii resistant to carbapenems, as well as a discussion of the clinical impact of HAIs in Brazilian intensive care units (ICUs). The first article aimed to determine the point prevalence of HAIs and identify factors associated with microbiologically confirmed infections in adult ICUs across Brazil. This multicenter study, conducted in 57 ICUs from different regions of the country, included 664 patients, of whom 47.7% had HAIs, with 68.1% acquired in the ICU. Only 47.2% of these infections were microbiologically confirmed. Mechanical ventilation and the use of polymyxins were identified as independent risk factors. The etiology of pneumonia, urinary tract infections, and bloodstream infections (BSIs) was predominantly associated with Pseudomonas aeruginosa and Acinetobacter baumannii; Candida spp.; and coagulase-negative Staphylococcus, respectively. The second article investigated the dissemination of resistance genes (by polymerase chain reaction – PCR) and pulsotypes (by pulsed-field gel electrophoresis – PFGE) in Klebsiella pneumoniae carbapenemase- producing (KPC) and Acinetobacter baumannii oxacillinase-producing (OXA-23) isolates from hospitals located in the North, Northeast, Southeast, and Central-West regions of Brazil. The blaOXA-23 and blaKPC genes were detected in 88.1% and 83.3% of A. baumannii and K. pneumoniae isolates, respectively, and all displayed multidrug- resistant profiles. Eleven distinct genotypes of A. baumannii were identified, with clone E detected in the Southeast (2016) and Central-West (2019) regions. No inter-regional dissemination of identical K. pneumoniae pulsotypes was observed. The third article, presented as a letter complementing a previous international study, expanded the discussion on the clinical impact of carbapenem-resistant Klebsiella pneumoniae infections. As part of this thesis, a letter was written discussing the study by Shao et al. (2024), which analyzed bloodstream infections in pediatric intensive care units in China. Our contribution compared those findings with data from our multicenter cohort of adult ICU patients with multidrug-resistant K. pneumoniae infections, emphasizing the high mortality associated with carbapenem-resistant strains. The letter highlighted similarities between pediatric and adult populations regarding risk factors and clinical outcomes, particularly in severe infections such as BSIs and pneumonia, and reinforced the urgent need for targeted strategies to combat antimicrobial resistance in both patient groups. Taken together, the three studies provide a comprehensive overview of HAIs in Brazilian ICUs, revealing their high prevalence, regional dissemination, and clinical impact, particularly regarding infections caused by multidrug-resistant K. pneumoniae. The findings underscore the importance of strengthening epidemiological surveillance policies, microbiological diagnosis, and rational antimicrobial use, as well as promoting the integration of national and international data to address the global challenge of bacterial resistance. 2026-02-10T00:00:00Z https://repositorio.ufu.br/handle/123456789/48017 Title: A ausência da proteína P21 em Trypanosoma cruzi impacta a invasão celular por tripomastigotas e modula a multiplicação e a expressão gênica de amastigotas intracelular de cepas filogeneticamente distintas Abstract: Trypanosoma cruzi is a protozoan parasite and the causative agent of Chagas disease, a neglected tropical disease with wide distribution in the Americas. This parasite displays high genetic variability, classified into Discrete Typing Units (DTUs), which are associated with biological, clinical, and molecular differences. Among the various factors involved in T. cruzi pathogenicity, the P21 protein stands out as a secreted glycoprotein implicated in modulating the inflammatory response, promoting host cell adhesion and invasion, and potentially regulating the parasite cell cycle. This study aimed to investigate the functional role of the P21 protein through targeted gene knockout in different T. cruzi strains using the CRISPR/Cas9 genome editing system, with a special focus on transcriptomic changes resulting from its absence. Knockout lines were generated in Y (TcII) and G (TcI) strains, representing distinct DTUs. The phenotypic impact of the knockout was evaluated in different developmental forms of the parasite, followed by global gene expression analysis using RNA-seq. Transcriptomic profiling revealed distinct expression patterns between knockout strains, with differentially expressed genes related to key processes such as cell adhesion, signal transduction, stress response, post-translational modifications, and the expression of surface proteins involved in virulence. These findings suggest that P21 plays a modulatory role in T. cruzi biology, with strain-specific effects on host-parasite interactions. The results contribute to a better understanding of P21 function during the parasite life cycle and highlight the utility of genome editing as a powerful tool for functional studies in trypanosomatids. 2025-11-28T00:00:00Z https://repositorio.ufu.br/handle/123456789/47734 Title: Investigação de produtos naturais potenciais na modulação da infecção por Trypanosoma cruzi em modelos de interface materno-fetal humana Abstract: Congenital Chagas disease is a neglected public health issue with limited treatment options. This study evaluated the potential of oleoresins (ORs) from Copaifera spp. and the extract and isolated compounds from Brazilian red propolis (BRP) against Trypanosoma cruzi infection in trophoblastic cells (BeWo lineage) and human villous placental explants (HVPE). Toxicity was assessed through histological and MTT assays, while the anti-T. cruzi potential was evaluated by proliferation, invasion, egress, and reversibility assays. The ultrastructure of treated trypomastigotes and amastigotes was examined by scanning and transmission electron microscopy. Production of reactive oxygen species (ROS) and lipid bodies were quantified in BeWo cells, and cytokines were measured in both BeWo cells and HVPE. ORs and BRP significantly reduced T. cruzi proliferation in BeWo cells and the parasitic load in HVPE. ORs induced ultrastructural changes in the parasite, including body torsion, flagellar rupture, and cytoplasmic disorganization, whereas BRP did not cause such changes. Both exhibited antioxidant activity, reducing ROS in infected BeWo cells, and BRP modulated lipid metabolism by decreasing lipid bodies. T. cruzi infection altered the cytokine profile in BeWo cells and HVPE; ORs upregulated suppressed cytokines in BeWo cells and downregulated elevated cytokines in HVPE. In conclusion, ORs from Copaifera spp. and BRP, at noncytotoxic concentrations, demonstrated promising potential as candidates for new therapies against congenital Chagas disease, with antiparasitic, antioxidant, and immunomodulatory effects. 2025-10-23T00:00:00Z https://repositorio.ufu.br/handle/123456789/47426 Title: Alterações ecocardiográficas de cães submetidos a protocolos quimioterápicos com doxorrubicina Abstract: Doxorubicin is a chemotherapeutic drug widely used in veterinary medicine due to its efficacy and affordability. Its cardiotoxic effects are well recognized, making it essential to seek strategies for its safe use. We conducted a systematic review and meta-analysis to evaluate the effects of this drug on the ejection fraction (EF) of dogs undergoing doxorubicin-based protocols. Thirteen studies reported echocardiographic alterations regardless of the route of administration (intravenous or intracoronary). The meta-analysis revealed an average EF reduction of 21.24%, underscoring its adverse impact on cardiac function. Additionally, a clinical study was conducted with 33 dogs treated at the Veterinary Hospital of the Federal University of Uberlândia and affiliated clinics, who were subjected to various chemotherapy protocols. The animals were evaluated at four time points (T0 to T3), with measurements of ejection fraction using the Teicholz (EFT) and Simpson (EFS) methods, fractional shortening (FS), and left ventricular dimensions in diastole and systole. Statistical analysis was performed using a linear mixed-effects model, considering time, doxorubicin use, preexisting heart disease, and their interactions. The results demonstrated statistically significant reductions in echocardiographic parameters in dogs treated with doxorubicin, either alone or in combination with other chemotherapeutic agents. Despite these changes, values remained within the physiological reference range for the species, and no clinical signs of cardiac dysfunction were observed. Chronic myxomatous mitral valve disease did not influence the occurrence of cardiotoxicity. Age, however, was a relevant factor, with adult dogs showing greater susceptibility. These findings suggest that doxorubicin cardiotoxicity exhibits a cumulative behavior and can be detected early through echocardiographic monitoring, particularly in patients exhibiting a trend toward declining cardiac function, even when values remain within normal limits. We conclude that doxorubicin is safe when used under cardiovascular monitoring, and serial surveillance of echocardiographic parameters is recommended, even in the absence of clinical signs of heart disease. 2025-09-26T00:00:00Z