DSpace Communidade:

Exposição pré-natal ao SARS-CoV-2, ativação imune materno-fetal e desfechos do neurodesenvolvimento infantil

2026-06-01T17:13:39Z

Título: Exposição pré-natal ao SARS-CoV-2, ativação imune materno-fetal e desfechos do neurodesenvolvimento infantil Autor(es): Kehdi, Renata Castro Abstract: This thesis investigates the relationship between maternal SARS-CoV-2 infection and the expression of pro-inflammatory markers in children up to 18 months of age. The research bases itself on the theory that the activation of the maternal immune system during pregnancy (MIA), due to exposure to pathogens such as SARS-CoV-2, can lead to the release of pro-inflammatory cytokines that remodel fetal brain connections, increasing the risk of neurodevelopmental disorders. In terms of methodology, the investigation uses the PLACOVGEN-BR cohort from the Neuropsychopharmacology Laboratory (LABNEURO/NPDM/UFC) in collaboration with the Assis Chateaubriand School Maternity (MEAC/UFC) and the Nucleus for Early Treatment and Stimulation (NUTEP), collecting data from pregnant women and their children between 2021 and 2023, involving the measurement of cytokines and chemokines in biospecimens via multiplex assay and the clinical evaluation of offspring neurodevelopment using gold-standard scales, such as the Bayley scale, to analyze cognitive, motor, and communication domains. The findings showed that prenatal exposure to SARS-CoV-2 was associated with a high frequency of neurodevelopmental delays at 24 months, particularly in the communication and motor domains. An increasing frequency of delays was observed between 6 and 24 months, especially in communication. Additionally, elevated levels of cytokines and chemokines in umbilical cord blood were associated with the observed outcomes, suggesting that perinatal inflammatory mediators, such as IFN-γ, TNF-α, IL-6, IL-8, IL-17, IL-1β, and CXCL10, may serve as early risk biomarkers for neurodevelopmental alterations in children exposed in utero to SARS-CoV-2. Taken together, these findings indicate that prenatal exposure to SARS-CoV-2 may adversely affect infant neurodevelopment, possibly through mechanisms involving maternal-fetal immune activation. These results reinforce the importance of longitudinal follow-up of children exposed during pregnancy and suggest the potential of perinatal inflammatory biomarkers for early risk identification. Tipo: Tese

Caracterização genética da Neoplasia Endócrina Múltipla do Tipo 1 no Baixo Jaguaribe, Ce: o impacto do rastreamento molecular da variante germinativa, MEN1 c.654G>T

2026-05-30T11:57:47Z

Título: Caracterização genética da Neoplasia Endócrina Múltipla do Tipo 1 no Baixo Jaguaribe, Ce: o impacto do rastreamento molecular da variante germinativa, MEN1 c.654G>T Autor(es): Pinheiro, Sabrina Magalhães Pedrosa Rocha Abstract: Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant inherited syndrome caused by pathogenic germline variants in the MEN1 gene, predisposing affected individuals to the development of endocrine and non-endocrine neoplasms, most commonly involving the parathyroid glands, pituitary gland, and duodenopancreatic endocrine cells. The clinical diagnosis of MEN1 is established when at least one of the following criteria is met: the presence of tumours affecting at least two MEN1-associated endocrine tissues; the occurrence of a single MEN1- associated tumour in a first-degree relative of an individual with a confirmed clinical diagnosis; or the identification of a pathogenic germline variant in the MEN1 gene. This study defined a geographical microregion in Baixo Jaguaribe, in the interior of Ceará, Brazil, to investigate the clinical variability of MEN1 cases in carriers of the pathogenic germline variant NM_001370259.2(MEN1):654+1G>T and to assess the impact of implementing molecular screening for this variant among at-risk relatives residing in the region. A care pathway was proposed, offering Sanger sequencing to patients with a clinical diagnosis and their at-risk relatives, in addition to the construction of pedigree charts for family investigation. The study included 50 individuals: five index cases with a confirmed clinical diagnosis and 45 relatives, all belonging to five families from the same geographical region, with no known parental relationship between the families. The index cases were genetically confirmed through identification of the pathogenic MEN1 variant. Among the 45 at-risk relatives, 18 (40.0%) had inherited the variant, whereas 27 (60.0%) did not carry it and were therefore excluded from clinical follow-up. Of the total number of variant carriers, ten were asymptomatic (43.5%). In the study cohort, the 23 individuals carrying the variant were divided into three groups: index cases (n = 5), with a mean age of 45.6 years (±15.2); relatives with clinical manifestations (n = 8), with a mean age of 48.1 years (±14.3); and asymptomatic family members (n = 10), with a mean age of 27.8 years (±13.9). Age analysis revealed a significant difference between symptomatic and asymptomatic family members (p = 0.027), suggesting that early access to genetic testing in this at-risk population may improve prognosis and reduce morbidity and mortality. Furthermore, the mean ages of the index cases and symptomatic relatives suggest a prolonged interval between symptom onset and referral to specialized care, delaying family screening, whereas the younger age of asymptomatic individuals underscores the importance of early diagnosis. No significant differences were observed between sexes. Regarding clinical manifestations, pituitary tumours were prevalent among index cases, with the classic MEN1 triad present in four of the five individuals. Among symptomatic relatives, primary hyperparathyroidism and gastroenteropancreatic neuroendocrine tumours were the most frequent initial manifestations. Skin lesions suggestive of collagenomas were identified in three individuals and may represent important clinical warning signs. The study involved active and systematic screening, including pedigree construction and genetic sequencing across multiple generations of five families, revealing a pattern of vertical transmission consistent with highly penetrant autosomal dominant inheritance. The identification of the same pathogenic variant in unrelated index cases, in a region without previously described MEN1 mutational hot spots, suggests a possible founder effect, potentially associated with geographical isolation and/or inbreeding characteristic of rural communities. Tipo: Tese

Inovação, evidências e aplicações clínicas da pele de tilápia (Oreochromis niloticus) na medicina veterinária: uma revisão de escopo

2026-05-21T12:16:56Z

Título: Inovação, evidências e aplicações clínicas da pele de tilápia (Oreochromis niloticus) na medicina veterinária: uma revisão de escopo Autor(es): Araripe, Lídia Sampaio Batista De Alencar Abstract: Nile tilapia (Oreochromis niloticus) skin is an innovative biomaterial in regenerative medicine due to its high type I collagen content, biocompatibility, and low cost. This thesis presents a scoping review conducted to map and synthesize scientific evidence on the clinical use of tilapia skin and its derivatives in veterinary medicine. The methodology followed the PRISMA-ScR guidelines and the Joanna Briggs Institute (JBI) recommendations, utilizing PubMed, Scopus, and Google Scholar databases. Twenty- nine studies published between 2015 and 2026 were included, encompassing original articles, case reports, and grey literature. The results demonstrate that Brazil leads scientific production in the field (approximately 65.5% of the studies). The main applications identified focus on two primary axes: cutaneous wounds (of various etiologies) and ophthalmology. Applications occurred in several species, such as dogs, cats, horses, donkeys, and wild animals. The biomaterial was used in various processing forms, including in natura, glycerol-preserved, lyophilized, and acellular dermal matrices. The evidence suggests that the use of tilapia skin as a xenograft promotes accelerated re-epithelialization, pain reduction, protection against contamination, and a decreased frequency of dressing changes, resulting in improved patient comfort and cost reduction. It is concluded that although the use of tilapia skin has shown excellent results in various applications and species without reports of adverse effects, there is still methodological heterogeneity and a predominance of case reports and experimental studies with small sample sizes. This highlights the need for further research involving standardized clinical trials and more robust cohorts to consolidate protocols in veterinary medicine. Tipo: Tese

Avaliação de risco cardiovascular em pacientes com artrite reumatoide: possível associação com atividade da doença, citocinas e a via NRF2/HO-1

2026-05-08T12:07:04Z

Título: Avaliação de risco cardiovascular em pacientes com artrite reumatoide: possível associação com atividade da doença, citocinas e a via NRF2/HO-1 Autor(es): Nobre, Christiane Aguiar Abstract: Cardiovascular risk assessment in patients with rheumatoid arthritis: possible association with disease activity, cytokines, and the NrF2/HO-1 pathway. Christiane Aguiar Nobre. Mirna Marques Bezerra. Doctoral thesis. Graduate Program in Translational Medicine. Center for Research and Development of Medicines, School of Medicine, UFC. Fortaleza, 2026. Introduction: Inflammation contributes to cardiovascular risk (CVR) in rheumatoid arthritis (RA), and oxidative stress mediated by erythroid factor 2 (Nrf2)/heme oxygenase 1 (HO-1) may also contribute to this process. Objective: To evaluate CVR, disease activity, serum cytokine levels, and Nrf2/HO-1 pathway expression in RA. Methods: Cross-sectional study with 120 participants, divided into RA and control groups. Clinical, laboratory, and ultrasound (US) data were collected from the heart and carotid arteries; cytokines were measured by ELISA (TNF- α, IL-1β, IL-6, IL-4, IL-10) and gene expression (mRNA) of Nrf2 and HO-1 by qRT-PCR. Disease activity was measured by DAS28, SDAI, and CDAI, while CVR was measured by serum pro-BNP, US, and clinical scores (Framingham and SCORE). Analyses were performed using SPSS v26.0 (p<0.05). Results: The sample was predominantly female (90%), with a mean age of 52 years. The control group had higher values for dyslipidemia (p=0.027), abdominal circumference (p=0.017), BMI (p=0.010), and blood glucose (p<0.001). In the RA group, the mean duration of the disease was 10.4 ± 7.5 years, with 63.3% positive for rheumatoid factor and/or anti-CCP. Regarding treatment, 91.7% used DMARDs, 21.7% used biologics, and 11.7% used target-specific agents. No differences were observed between the groups in clinical CVR scores and US findings. However, pro-BNP levels were higher in RA (p=0.009). We observed higher levels of IL-6 (p=0.002) and IL-10 (p=0.004), with a reduction in IL-1β (p=0.001). We found an increase in mRNA-Nrf2 (p<0.001) and a reduction in mRNA-HO-1 (p=0.030). Disease lasting more than 10 years was associated with hypertension (p=0.023), higher DAS28-ESR (p=0.017) and SDAI (p=0.025), as well as more frequent use of antihypertensive drugs (p<0.001), statins (p=0.011), hypoglycemic agents (p=0.038), and higher blood glucose levels (p=0.029). CDAI correlated with higher IL-6 levels (p=0.033) and DAS28-PCR with lower education (p=0.038), longer disease duration (p=0.012), ventricular dysfunction (p=0.044), and elevated triglycerides (p=0.030). Conclusion: Patients with RA presented with Nrf2/HO-1 pathway dysregulation and elevated pro-BNP. Higher disease activity and longer disease duration were associated with a higher prevalence of comorbidities and cardiovascular complications in RA. Tipo: Tese