Epidemiological and Financial Aspects of Hospitalizations for Bacterial Meningitis in Brazil.

Introduction: Understanding the epidemiology and cost implications of acute bacterial meningitis is crucial for effective health planning, timely treatment implementation, and comprehensive patient support measures, as well as for determining appropriate hospital expenses. Therefore, we conducted an analysis of hospitalization cases for bacterial meningitis in Brazil from January 2008 to December 2019. Methods: This is a descriptive ecological study that utilized the Hospital Information System of Brazil's National Unified Health System (SIH/SUS) database. The variables included sex, region, age group, hospitalizations, deaths, lethality rate, and hospital service expenses. The data were tabulated to focus specifically on the epidemiological aspect of bacterial meningitis. Results: During the study period, there were 20,207 hospitalizations for bacterial meningitis in Brazil. Men accounted for a higher number of cases, with 11,690 (57.67%), while women had a higher lethality rate of 10.64%. The Southeast region had the highest percentage of both hospitalizations (45.78%) and deaths (46.42%). Bacterial meningitis remains an important cause of morbidity and mortality, particularly in children under 5 years of age. Notably, the elderly and the Northeast region showed higher rates of lethality. The total expenditure on hospital services exceeded 43 million in Brazilian real, with the highest expenditure observed in 2019 and the lowest in 2011. Conclusion: A higher prevalence of the disease was observed in males, in children under 1-year-old and in the southeast region. Hospital expenditures were found to be substantial and increasing over time, underscoring the significance of early diagnosis and the promotion of vaccination campaigns.

Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading.

The present study aimed to compare levels of VEGFR2 and MMP-9 among control, epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) groups. We analyzed 48 patients with oral leukoplakia (OL), 20 patients with OSCC and 21 patients without OL and OSCC. Immunohistochemistry of VEGFR2 and MMP9 were performed and compared among groups. Analysis of tissue immunolocalization of VEGFR2 and MMP-9 assumed non-parametrical distribution and comparison between groups was performed using the Mann-Whitney and Kruskal-Wallis statistical tests. VEGFR2 and MMP9 immunoexpression appeared to correlate with the degree of dysplasia and was observed to increase in lesions with more severe dysplasia as compared to those with lower degrees of dysplasia. Immunoreactivity of MMP-9 was lower in the OL samples compared to the OSCC samples (p = 0.004). We observed no difference in VEGFR2 protein levels between OL and OSCC samples. A positive correlation was found between VEGFR2 and MMP-9 in OL samples (r = +0.452, p = 0.001), however, no correlation was found in OSCC samples (r = -0.042, p = 0.861). In conclusion, the results of the current study suggest that expression of MMP9 and VEGFR2 is associated with ED grading and MMP9 levels are increased in OSCC.

Resveratrol attenuates hepatic steatosis in high-fat fed mice by decreasing lipogenesis and inflammation.

OBJECTIVE: Resveratrol (RSV) is the most studied natural compound that activates sirtuins, which produce beneficial metabolic effects on lipid and glucose metabolism. The aim of the present study was to investigate the role of resveratrol in preventing nonalcoholic fatty liver disease (NAFLD) and expression of liver inflammatory markers in mice treated with a high-fat diet. METHODS AND PROCEDURES: Eighteen male mice were divided into three groups and fed for 60 d with a standard diet (ST), high-fat diet (HFD), or high-fat diet plus resveratrol (HFD + RSV, 30 mg/kg/d). Body weight, food intake, and serum total cholesterol, triacylglycerol, insulin, alanine transaminase (ALT), and aspartate aminotransferase (AST) were evaluated. Liver histology was analyzed. Expression of ACC, PPAR-γ, ChREBP, SREBP-1 c, CPT-1, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), NF-κB, interleukin 1 ß (IL-1 ß), and SIRT1 were evaluated by quantitative real-time reverse transcriptase PCR (qRT-PCR). RESULTS: The major finding of the present study was that RSV reduced body fat, total cholesterol, triacylglycerol, transaminases, and insulin plasma level. These results were accompanied with a significant reduction in TNF-α, IL-6, and NF-κB mRNA expression in the liver. Analyses of liver adipogenesis related genes indicated that ACC, PPAR-γ, and SREBP-1 mRNA expression were significantly suppressed in HFD + RSV mice. In addition, we observed increased expression of SIRT1 in the HFD + RSV group. CONCLUSIONS: We observed that treatment with resveratrol improved lipid metabolism, and decreased NAFLD and pro-inflammatory profile in liver of mice with obesity-inducible diets. These data suggest an important clinical application of RSV in preventing liver diseases.

Sirtuins and cancer: new insights and cell signaling.

Sirtuins are involved in the control of the cell cycle and regulation of gene transcription. While some sirtuins have tumor suppressor effects, others regulate tumors metabolism. Within this perspective, the present article is a review of the current role of sirtuins in the etiology and physiopathology of cancer. Sirtuins show strong potential to become a valuable predictive and prognostic marker for cancer and are eligible as therapeutic targets for a variety of tumors. Investigation of new molecules able to modulate sirtuins activity must be encouraged.

Analysis of the normative conditions of oral health, depression and serotonin-transporter-linked promoter region polymorphisms in an elderly population.

AIM: To investigate the association between depression, the normative conditions of oral health and serotonin-transporter-linked promoter region (5-HTTLPR) polymorphisms in a community-dwelling elderly sample. METHODS: Elderly adults living in a community (n=200) were submitted to an oral clinical examination. Depression was assessed using the 15-item Geriatric Depression Scale. The 5-HTTLPR was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Associations between the biomarkers and clinical covariates were assessed by bivariate and multivariate statistical tests. Statistical significance was set at P<0.05. RESULTS: The prevalence of dental caries, periodontal disease, edentulism and oral mucosal lesions was 51.2%, 20.8%, 58.0% and 21.5%, respectively. The prevalence of depression was 21.5%. A higher frequency of the S allele was recorded in older individuals with depression (P=0.017). The present findings showed no significant association between depression and the normative conditions of oral health. The observed allelic polymorphisms were 44% S and 56% L, respectively. Genotypic variants were 33.5% LL, 45.0% SL and 21.5% SS. Individuals carrying the SS genotype showed a significantly high prevalence of periodontal disease (prevalence ratio=3.077, CI 95%=1.008-9.393, P=0.048). CONCLUSION: The present findings suggest that depressive community-dwelling older individuals did not show any association with alterations of oral health normative conditions. However, the SS genotypic polymorphic variant of 5-HTTLPR seems to contribute to the occurrence of periodontal disease in the elderly.

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients.

Recently, high-risk human papillomavirus (HPV) has emerged as a possible agent associated with head and neck squamous cell carcinoma (HNSCC) in younger patients. Therefore, the purpose of the present study was to assess the effect of age on the distribution of HPV-16/18 in HNSCC, together with the impact of the virus on patient prognosis. A longitudinal prospective study was used adjusted for age, gender, TNM staging, smoking status and alcohol consumption. HPV was detected by PCR with consensus primers. Results showed there was no difference in the frequency of HPV-16/18 positivity when younger patients were compared to the older patients. No association was found among high-risk HPV positivity, gender, smoking habit and anatomical site. High-risk HPV was associated with advanced TNM in bivariate analyses; however, it did not impact on survival. Only TNM staging was associated with risk of mortality. Our study supports the theory that age does not affect the presence of HPV-16/18 in HNSCC and has no impact on patient prognosis. The incidence of HNSCC among patients under the age of 45 years is reportedly on the increase worldwide. The factors associated with HNSCC in younger adults are not well established. Findings of this study indicate that HPV-16/18 may not play a role in HNSCC patients under the age of 45 years.

Infiltrating CD57+ inflammatory cells in head and neck squamous cell carcinoma: clinicopathological analysis and prognostic significance.

This study investigated the immunodetection of CD57+ inflammatory cells in patients with head and neck squamous cell carcinoma (HNSCC) and its association with clinicopathological parameters and overall survival. Data collected from the morphological analysis and immunohistochemical reaction testing of archived HNSCC specimens (n=70) were statistically analyzed by bivariate and multivariate statistical testing at a significance level of P<0.05. The results indicate that CD57+ inflammatory cells predominate within the peritumoral stroma of HNSCC lesions and the existence of two significant relationships: between high CD57+ cell density and the development of a tumor of a large size [odds ratio (OR)=5.610, 95% confidence interval (CI)=1.516-20.763) and between high CD57+ cell density and the development of locoregional metastatic disease (OR=3.401, 95% CI=1.162-9.951). A significant difference in the rate of survival was detected only in HNSCC patients that presented large size tumors (OR=4.747, 95% CI=1.281-17.594). Together, these results suggest that although high CD57+ inflammatory cell density is associated with HNSCC lesions of greater clinical severity, the variable of cell density is not an independent predictor of HNSCC patient survival. Our findings also suggest that the relatively aggressive infiltration of CD57+ inflammatory cells in the peritumoral stroma of head and neck carcinomas may contribute to an ineffective locoregional antitumoral response.

A high HIF-1α expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients.

The aim of the present study was to evaluate the role of HIF-1α genetic polymorphisms and protein expression in the development of metastasis in upper aerodigestive tract cancer (UADTC) patients. The expression of pro-angiogenic markers was also evaluated. Protein expression was analysed using immunohistochemistry, and RFLP analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 52 patients with UADTC. Primary lesions were divided into 2 groups according to the absence or presence of metastasis. Lymph node samples were divided into 3 groups: metastatic lymph nodes, non-metastatic lymph nodes (both derived from patients with metastatic disease), and control lymph nodes, which were obtained from patients without any metastasis. The allele T was more frequently found in patients with metastatic disease. HIF-1α protein expression in the lymph nodes was increased in the presence of the T allele. Metastatic lymph nodes showed lower levels of HIF-1α, VEGFR1, and MMP-9 proteins compared to lymph nodes without metastasis, while VEGFR2 protein levels were increased. In agreement, HIF-1α expression was correlated with MMP-9. Cox regression analysis demonstrated that higher HIF-1α and MMP-9 protein expression levels and GA and GG genotypes were associated with poor survival. Our findings show that the C1772T and G1790A polymorphisms of the HIF-1α gene are associated with increased expression of the HIF-1α protein in UADTC. The present data indicate that non-metastatic tissues express higher levels of HIF-1α, VEGFR1, and MMP-9, while in metastatic lymph nodes, VEGFR2 protein expression is elevated. The present study also shows that the HIF-1α G1790A polymorphism and its protein expression have an impact on the prognosis of UADTC patients.

Effect of age on the association between p16CDKN2A methylation and DNMT3B polymorphism in head and neck carcinoma and patient survival.

De novo DNA methylation is a relevant epigenetic mechanism, which represses gene transcription and commonly inactivates tumor suppressor genes in carcinogenesis. A single nucleotide polymorphism of DNMT3B, C46359T (-149C-->T) was reported to modulate individual's susceptibility to cancer. We investigated the role of this polymorphic variant regarding the methylation status of the p16CDKN2A gene in young and older patients with head and neck squamous cell carcinoma (HNCC) matched by the TNM staging system, together with its impact on patients survival. The results showed that the presence of the allele T of the polymorphism DNMT3B (-149C-->T) was associated with advanced TNM staging and smoking habit, but no association was found between this polymorphisms and DNMT3B immunostaining. While p16CDKN2A methylation was significantly associated with smoking habit in older patients, this parameter was associated with family history of cancer in young patients. Moreover, in older patients the absence of p16CDKN2A promoter methylation had a negative impact on survival. In conclusion, nucleotide polymorphism of DNMT3B is not associated with methylation of p16CDKN2A gene in HNSCC. The association of p16CDKN2A gene methylation with smoking, family history of cancer and survival is dependent on age.

Immunohistochemical expression of interleukin-4, -6, -8, and -12 in inflammatory cells in surrounding invasive front of oral squamous cell carcinoma.

BACKGROUND: Cytokines play important roles in the diverse interactions between tumor microenvironment and malignant cells. This study evaluated the association of interleukin (IL)-4, -6, -8, and -12 expressions and clinicopathologic parameters of 35 primary oral squamous cell carcinomas (OSCCs). METHODS: Patients were staged according to the TNM clinical staging. Malignancy grading of invasive front was evaluated in hematoxylin-eosin (H&E)-stained slides. Immunohistochemical technique was performed on frozen tissue sections. Association between clinicopathologic parameters and IL expression were analyzed using nonparametric Kruskal-Wallis (alpha = 0.05) and Mann-Whitney U tests, with Bonferroni correction. Correlations between interleukins were analyzed by the Spearman coefficient. RESULTS: Expression of ILs was verified in all samples; however, this finding was not related to clinicopathologic parameters. It was not the observed correlation between ILs. CONCLUSIONS: Expression of IL-4, -6, -8, and -12 in the invasive front of OSCC is not involved with the clinicopathologic parameters of the disease.