https://repositorio.ufpb.br/jspui/handle/tede/1693 PPGBCM 2026-09-21T20:00:56Z https://repositorio.ufpb.br/jspui/handle/123456789/39187 Título: Dinâmica epidemiológica, genômica e espacial do SARS-CoV-2 no estado da Paraíba de 2020 a 2024 Autor(es): Carneiro, Thiago Franco de Oliveira Orientador: Bezerra, João Felipe Abstract: The COVID-19 pandemic represented one of the greatest public health challenges of the 21st century, highlighting the importance of epidemiological and genomic surveillance for monitoring SARS-CoV-2 transmission dynamics and evolution. This study aimed to analyze, in an integrated manner, the epidemiological and molecular dynamics of COVID-19 in Paraíba State, Brazil, from March 2020 to December 2024. This was an observational, ecological study with a mixed design (retrospective and prospective) and a quantitative approach, based on the analysis of secondary epidemiological and genomic surveillance data, as well as the generation of primary SARS-CoV-2 genomic data. Data on cases and deaths were obtained from the SIVEP-Gripe and e-SUS Notifica systems, and genomic data were retrieved from the GISAID platform. During the study period, 727,242 confirmed COVID-19 cases and 10,690 deaths were recorded in Paraíba State. Of all confirmed cases, 591,470 (81.33%) were classified based on laboratory criteria. Among 444,069 real-time RT-PCR tests included in the study, 140,460 were positive, corresponding to a positivity rate of 31.63%. Annual cumulative incidence was 4,752.58 per 100,000 inhabitants in 2020, peaked at 6,808.34 per 100,000 in 2021, declined to 5,878.46 per 100,000 in 2022, and dropped sharply in 2023 (327.84 per 100,000) and 2024 (169.71 per 100,000). Genomic surveillance comprised 4,114 genomes from 174 municipalities (78.03% of the state), of which 96.89% achieved genome coverage above 95%. Successive replacement of B.1-related lineages by the Gamma, Delta, and later Omicron variants and their sublineages was observed. Gamma predominance coincided with the period of greatest epidemiological impact, whereas Omicron introduction, particularly BA.1, was associated with a marked increase in cases without a proportional rise in deaths. Higher lethality was observed among males, who had 41% greater odds of death than females (OR = 1.41; 95% CI: 1.33–1.48), and mortality increased markedly with age, reaching OR = 66.48 (95% CI: 56.76–77.90) among individuals aged 80 years or older. Despite broad territorial coverage and high-quality genomes, the interval between sample collection and sequence submission to GISAID was prolonged, with a mean of 113.49 days and a median of 66 days (IQR: 41–148), limiting its usefulness for timely public health action. In conclusion, the integration of epidemiological and genomic surveillance was essential to understanding COVID-19 dynamics in Paraíba State, highlighting the role of viral variants, population immunity, and operational capacity in shaping the pandemic impact. These findings reinforce the need to strengthen genomic surveillance as a strategic component of preparedness for future public health emergencies. Editor: Universidade Federal da Paraíba Tipo: Dissertação 2026-03-26T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37770 Título: Avaliação da expressão do gene TP53 em amostras de pacientes com câncer colorretal e sua correlação com fatores prognósticos Autor(es): Tomaz, Alécia Coura Orientador: Martina, Glaucia Verissimo Faheina Abstract: Colorectal cancer (CRC) is a neoplasm that affects the large intestine in its segments of the colon, rectum and anus. It is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. Some of the risk factors for colorectal cancer include: high fat diet, sedentary lifestyle, obesity, smoking and excessive alcohol consumption. Among the genes that are frequently mutated, alterations in the TP53 gene are considered one of the main genetic alterations related to the development of CRC. Sociodemographic factors such as ethnicity and socioeconomic status are known to influence the incidence, stage, diagnosis, survival and mortality of this cancer. The aim of this study was to carry out an ambispective cohort study of patients with Colorectal Cancer using paraffin-blocked samples. As well as analyzing TP53 gene expression by real-time PCR in fresh samples from patients at Hospital Napoleão Laureano in João Pessoa/PB, Brazil. Statistical analyzes were performed using SPSS® software, version 22.0 and the public domain program OpenEpi, version 3.01. Association tests were performed, such as Pearson's Chi-square and Fisher's Exact Test, the P value considered statistically significant <0.05. Positive p53 staining was observed in 46.5% of the 43 patient samples analyzed by immunohistochemistry, and 53.5% were negative. Of the samples analyzed for immunohistochemistry, it was found that 55.8% of the patients were female, with a mean age above 60 years (79.1%). The most frequent ethnicity was brown people (81.4%). Regarding the laterality of the tumor, the region of the left colon was more frequent (60.4%), and the most present histological grade was the moderately differentiated (88.3%). As for the morphological pattern, the tubular was the most frequent (74.4%). With regard to Internship, II was the most observed in the study population (81.4%). Metastasis in lymph nodes was absent in most of the individuals analyzed (51.1%). Patients who presented positive marking for carcinoembryonic antigen (CEA) corresponded to 30.2%, considered positive when CEA > 4.0 ng/ml. There was no significant association between p53 expression and any of the analyzed variables (gender, age, education, ethnicity, location, histological grade, histological pattern, stage and positive quantification for CEA). In the analyzes of TP53 gene expression by real-time PCR, performed in fresh samples (n=10), a higher expression of TP53 was observed in normal tissues (adjacent to the tumor) in relation to tumor tissue (p< 0.05 ). The analysis of data from this cohort allowed us to better understand the profile of the disease, highlighting the main sociodemographic and clinical factors associated with the disease, making it possible to assist in possible preventive and management practices for the patient. However, it was not possible to associate p53 expression with other markers such as CEA, or with other pathological clinical factors. More comprehensive studies with a larger number of patients may possibly better clarify the contribution of p53 as a biomarker for colorectal cancer. Editor: Universidade Federal da Paraíba Tipo: Dissertação 2023-03-31T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37680 Título: Avaliação dos efeitos tóxicos da peçonha de Bothrops jararacussu sobre embriões e larvas de peixe-zebra (Danio rerio) Autor(es): Silva, Layssa Gualberto da Orientador: Salvador, Daniela Priscila Marchi Abstract: Ophidism is a neglected disease responsible for affecting approximately 2.7 million people worldwide, mainly affecting tropical and subtropical countries. In Brazil, 90% of the reported and identified cases of these accidents are caused by snakes of the Bothrops genus. Bothrops jararacussu has clinical relevance, and its venom is composed of substances capable of triggering local and systemic effects, culminating in the development of morbidities and/or mortality in the affected individual. The present study aimed to evaluate the toxic effects triggered by the presence of the venom on the zebrafish embryo and larvae model system. The stability of B. jararacussu venom under the conditions used in the toxicity experiments in zebrafish embryos and larvae was evaluated by measuring the prothrombin and activated partial thromboplastin times of citrated human plasma in the presence of different amounts of the venom and in different exposure times. In addition, the mortality rate, morphological alterations, spontaneous movements and heart beats of embryos were evaluated, as well as certain parameters of toxicity and alterations in the biochemical profile of the biomarker enzymes of toxicity (glutathione-S-transferase, catalase, lactate dehydrogenase, and acetylcholinesterase) of zebrafish larvae after exposure to B. jararacussu venom. Acute toxicity was assessed by semi-static exposure of zebrafish embryos and larvae to the venom for 96 hours. Our results indicated that B. jararacussu venom causes toxicity in zebrafish embryos and larvae, causing embryo mortality in the first 24 hours of exposure, in addition to altering the number of spontaneous tail movements and acetylcholinesterase activity. Changes in the activities of the other antioxidant enzymes evaluated were also verified. The evaluation of these results allows us to suggest that the toxic effects caused by the presence of the venom in the early stages of zebrafish development are mediated, by neurotoxic action, induction of oxidative and metabolic stress possibly caused by low molecular weight components and/or proteins that makes up the venom. Toxinological evaluations using zebrafish as a model are scarce, however, this study presented promising results that encouraged the development of future research in snake toxinology using this animal as a model organism. Editor: Universidade Federal da Paraíba Tipo: Dissertação 2022-02-25T00:00:00Z https://repositorio.ufpb.br/jspui/handle/123456789/37679 Título: Avaliação dos efeitos terapêuticos de Lactococcus lactis carreadora do vetor de expressão eucariótica que codifica para scFv anti-TNFa em modelo de colite induzida por TNBS Autor(es): Viana, Giovana Cristina Santana Orientador: Almeida, Juliana Franco Abstract: Crohn’s disease (CD) belongs to the group of infectious intestinal diseases (IBD), and is characterized by an intestinal infection caused by severe infections of the mucosa, which cannot be cured by clinical or surgical treatment and which can affect the entire gastrointestinal tract. TNF-α plays a fundamental role in the disease, being considered the best therapeutic target. However, an intravenous route of immunotherapies causes immunogenicity and systemic effects. To circumvent these restrictions, local delivery of these drugs could benefit patients, restrict therapy to the inflammatory site. The development of Lactococcus lactis cephas is capable of providing a eukaryotic expression vector that encodes a single chain variable fragment (scFv) of antibody represents a new strategy for the analysis of a more effective alternative therapy for isolated expression in the intestine, against CD. In this way, the objective of this work was to evaluate the therapeutic effects of fragments of scFv use anti-TNF-α used locally in the intestinal mucosa using L. lactis as a vehicle for delivery of vectors in the intestinal mucosa, in the experimental Crohn's disease model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Thus, the effect of producing these filters directly on the intestinal mucosa was analyzed. Female BALB c mice were used, with experimental colitis induction by TNBS for four weeks. The L. lactis culture was administered orally in the last 5 days of the protocol. No day after the last day of treatment, the animals were sacrificed and with different temperature variations. He observed an improvement in the group treated with L. lactis FnBPA + (pValac :: anti-TNFα) in the macroscopic parameters of the disease in relation to the unused groups. In the histological analysis, the beneficial effect of the treatment was better observed in the proximal region, with reduction of the inflammatory infiltrate and maintenance of the mucous layer. With these results, we conclude the treatment with pValac :: anti-TNFα has a mitigating effect on the experimental collection model, and the most recent studies are adequate to elucidate the molecular mechanisms used by the effect and, thus demonstrating a strategy based on in delivering DNA. Editor: Universidade Federal da Paraíba Tipo: Dissertação 2020-02-28T00:00:00Z