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Doença valvar cardíaca em pacientes com morbidades metabólicas: uma análise histopatológica e metagenômica. Estudo de série de casos

2026-03-20T11:56:04Z

Título: Doença valvar cardíaca em pacientes com morbidades metabólicas: uma análise histopatológica e metagenômica. Estudo de série de casos Autor(es): Pinho Filho, João Eudes Teixeira Abstract: Heart disease has been the leading cause of death worldwide. Among these conditions, calcification of heart valves stands out, occurring due to a degenerative process influenced by infections associated with an inflammatory state. In this context, the objective of this study was to identify the microorganisms present in heart valves removed from cardiac patients through metagenomic analysis. This is an observational, cross-sectional, case-control study of samples collected from heart valves of patients undergoing valve replacement surgery. 27 valve leaflets from patients with valvular heart disease and 9 from the control group were histologically analyzed for the presence of inflammation and mineralizations. Giemsa and Grocott histochemical analyses were performed to evaluate possible bacteria and fungi present in the sample. The DNAs from the heart valve samples were extracted and frozen for PCR analysis. Furthermore, metagenomic sequencing of the 16S and 18S rRNA regions was performed, followed by bioinformatic analysis. The results demonstrated an unfavorable cardiometabolic profile, with hyperglycemia and reduced HDL cholesterol. Histologically, diffuse fibrosis, chronic inflammation, myxoid degeneration, and calcification predominated. Histochemical analysis with Groccot and Giemsa staining identified a significant frequency of structures compatible with microorganisms, especially bacteria and fungi. Metagenomic analysis identified potentially opportunistic bacteria and fungi, including Staphylococcus, Sphingomonas, Actinotignum, Cutaneotrichosporon, and Apiotrichum. It is concluded that the valvular heart diseases analyzed present a multifactorial character, involving interactions between metabolic, inflammatory, degenerative, and microbiological alterations, highlighting the relevance of metagenomics as a complementary tool in the investigation of valvular heart diseases. Tipo: Tese

Avaliação dos efeitos de p-cimeno em câncer: revisão de escopo e estudo In vitro

2026-02-20T17:06:58Z

Título: Avaliação dos efeitos de p-cimeno em câncer: revisão de escopo e estudo In vitro Autor(es): Viana, Khalil Fernandes Abstract: Conventional oncological therapies tend to mutilate patients and generate pharmacological resistance and adverse effects. The use of natural compounds stands out as an alternative in this therapy, as it minimizes the deleterious effects and enhances the action of chemotherapeutics, acting as an adjuvant. P-cymene (pC), a monoterpene present in several plants, has already been evaluated in preclinical cancer studies, showing preventive and therapeutic effects. However, these findings need to be better mapped and analyzed in order to elucidate the best strategies for using this compound in cancer therapy. This thesis aimed to review and map the published findings on the actions of pC in cancer, as well as to evaluate the in vitro activity of this compound in two oral cancer cell lines. For this, a scoping review was performed using PRISMA-ScR as a guide and using the bibliographic databases Embase, Scopus, Pubmed and Web of Science for the selection of studies. The laboratory study was based on cell cultures of the following cell lines: UM-HACC-2A (salivary adenoid cystic carcinoma), in which cell viability assays (Live/Dead assay method) were performed to obtain the IC50 of pC, immunofluorescence of NFκB and Ki-67, cell migration and analysis of the nuclear area; SCC-4 (oral squamous cell carcinoma), in which cell viability assays (MTT method), gene expression of Caspases 3 and 9, Bcl-2 and Akt, immunocytochemistry of PI3K, Ki-67 and Akt proteins, as well as cell migration were performed; and HaCat (normal keratinocytes), as control. The Shapiro-Wilk test, t-test, Mann-Whitney test and nonlinear regression were the statistical methods applied, with a significance level of 5% (p<0.05) adopted for all analyses. The results of the scoping review revealed that 93.7% of the included in vitro studies showed pC IC50 values considered to be of low cytotoxic potential by the National Cancer Institute (NCI), with a mean value of 178.43 μg/ml, being tested in colorectal, breast, lung, liver, cervical, skin, fibrosarcoma and melanoma cancers and acting mainly through non-cytotoxic mechanisms, such as alteration of cell signaling pathways (inhibition of ERK1/2 and p38 MAPK and activation of TIMP-1), modulation of the tumor microenvironment (reduction of SOD, increase of IL-6 and reduction of IL-1) and inhibition of invasion (reduction of MMP-9), and secondarily through cytotoxic mechanisms, such as DNA damage (increase of 8-OHdG) and plasma membrane (increase of malondialdehyde), and increase of Caspase-3 activity. Animal studies have shown significant results in reducing the incidence of tumors in colorectal cancer and tumor size in colorectal cancer and melanoma. The results of the in vitro study demonstrated low cytotoxicity of pC in UM-HACC-2A (IC50=664.7 μg/ml), in SCC-4 (IC50=573.6μg/ml) and in normal keratinocytes (IC50=694,6 μg/ml), with a selectivity index (SI) of 1.12. In the UM-HACC-2A cell line, significant inhibition of the expression of NFκB (p=0.026) and Ki-67 (p=0.005) proteins was observed, as well as a reduction in nuclear area (p<0.0001), but there was no statistically significant difference in the migration of UM-HACC-2A cells. In SSC-4 cells, there was inhibition of cell migration (p=0.0005), reduction in the expression of PI3K, Ki-67 and Akt proteins (p=0.0286); however, no significant changes were observed in the gene expression of Caspase 3 and 9, Bcl-2 and Akt. It is concluded that, although pC presents low direct cytotoxicity against tumor cells, its effects on cell signaling pathways, tumor microenvironment, cell invasion and migration processes, as well as chemoprevention in animal models, suggest its use as an adjuvant agent in oncological therapy, acting as a modulator of tumor progression and potentially increasing the efficacy of conventional cytotoxic therapies. Continued studies, with emphasis on in vivo models and proteomic analyses, are essential to deepen the knowledge about its mechanisms of action and therapeutic potential. Tipo: Tese

Dimorfismo sexual em exames de imagem de estruturas neurocranianas: revisões sistemáticas, análise morfológica e morfométrica tridimensional da sela túrcica e forame magno e predição do sexo por aprendizado de máquina

2026-01-21T16:04:38Z

Título: Dimorfismo sexual em exames de imagem de estruturas neurocranianas: revisões sistemáticas, análise morfológica e morfométrica tridimensional da sela túrcica e forame magno e predição do sexo por aprendizado de máquina Autor(es): Ribeiro, Esther Carneiro Abstract: Sexual dimorphism in neurocranial structures plays a relevant role in estimating biological sex and is of great interest in forensic anthropology and human identification. This study aimed to evaluate sexual dimorphism based on linear, volumetric, and morphological parameters of the sella turcica (ST) and foramen magnum (FM) in multislice computed tomography (MSCT) scans, integrating systematic reviews, three-dimensional analyses, and machine learning algorithms. Initially, two systematic reviews were conducted and registered in the PROSPERO database. These reviews synthesized evidence on sexual dimorphism in neurocranial structures and on the role of the ST in sex estimation among non-syndromic individuals. Searches across multiple databases resulted in meta-analyses of linear and volumetric measurements. The findings revealed significantly smaller neurocranial dimensions in females, with high reliability for measurements obtained through tomography. For the ST, length and diameter differed between sexes, although the certainty of the evidence was rated very low, highlighting the need for further studies with greater methodological standardization. In the analytical phase, 200 MSCT scans from adult individuals from northern and northeastern Brazil were examined to assess ST morphology according to the classifications proposed by Axelsson and Yasa. The normal, oblique anterior, round, and flat shapes were associated with sex among individuals under 30 years old, underscoring the potential of ST morphology as a complementary marker of sexual dimorphism. Subsequently, three-dimensional measurements of the ST and FM were obtained from 228 adult scans using semi-automatic segmentation and standardized cranial orientation with ITK-SNAP and 3D Slicer software. Intra-examiner reproducibility was high (ICC 0.81–0.98). All FM dimensions and most ST measurements were smaller in females, with statistically significant differences. Discriminant formulas yielded an area under the curve (AUC) of 0.798 (95% CI: 0.740–0.855), and machine learning algorithms—particularly the Support Vector Machine (SVM)—achieved moderate performance, with AUC values up to 0.8351 (± 0.0888) when both structures were evaluated together. The findings confirmed the sexual dimorphism of the ST and FM, reinforcing their value as useful anatomical markers for sex estimation. The integration of three-dimensional analyses and machine learning models demonstrated potential to enhance the accuracy of sex classification and broaden the applicability of imaging techniques in forensic anthropology. Although the results are promising, consolidation of these approaches requires external validation across diverse populations and standardization of acquisition and segmentation protocols. Tipo: Tese

Mortalidade por câncer de boca e faringe em Natal/RN no período de 1981 a 1995

2025-12-29T14:41:41Z

Título: Mortalidade por câncer de boca e faringe em Natal/RN no período de 1981 a 1995 Autor(es): Almeida, Maria Eneide Leitão de Abstract: This is an epidemiological time tendency study about the mortality of mouth and pharynx câncer on the population of the city of Natal, from 1981 to 1995. Many considerations were taken about the main risk factors for these types of câncer and their epidemiological situation. We intended to analyze comparatively the relation among the tendency of mortality caused by mouth and pharynx câncer and the other neoplasias within the established period. The data were collected from the obituary of the dead citizens of Natal from 1981 to 1995 by means of the Mortality Information System of Rio Grande do Norte, available in CD-ROM, and also from the demographic censi of 1980 and 1991. In order to organize the analisis, the data were divided into consecutive groups of three years (Triennium) and the main variables were sex, age and the anatomical sites attacked by the câncer. The potential years of life lost (PYLL) due to the occurrence of mouth and pharynx câncer were also estimated and recorded. The results showed that in the first trienium (1981-83), the risks of dying in Natal decreased from 756.93 to 630.96 per 100,000 men and from 528.01 to 417.00 per 100,000 women. Nevertheless, considering the mouth and pharynx câncer, these rates assumed and ascending aspect, raising from 2.60 to 6.66 among men and from 1.55 to 2.08 among the women. The proportional mortality rate (%) caused by malignant neoplasias in the last triennium (1993-95) was 12.4% among men and 16.9% among the women, showing a clear ascending tendency throughout the studied period. The most common anatomical sites, in men and women, attacked by the malignant neoplasias of the mouth (not especifíed) and the average of ages was from 65 to 69 years old. There was a significant subtration of 1,167.5 potential years of life from the population of the city of Natal, and 977.5 years were taken from the men and 190.0 from the women. Tipo: Dissertação