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Integração de abordagens ômicas na investigação de alterações metabólicas associadas à hepatite D

2026-08-06T06:19:49Z

Title: Integração de abordagens ômicas na investigação de alterações metabólicas associadas à hepatite D Abstract: Background and aims: Hepatitis D virus (HDV) is a single-stranded circular RNA satellite virus with hepatocyte-specific tropism that occurs in the presence of hepatitis B virus (HBV), being functionally dependent on it to complete its infectious cycle. Transmission occurs predominantly via the parenteral route and may present as simultaneous coinfection or as superinfection in individuals chronically infected with HBV, the latter being associated with more severe clinical outcomes, including early cirrhosis and an increased risk of hepatocellular carcinoma. Given the central role of the liver in metabolic regulation, HDV infection is expected to induce alterations in systemic metabolism. However, to date, comprehensive characterization of these alterations, particularly through omics-based approaches, remains limited. In this context, this study aimed to investigate serum metabolomic and lipidomic signatures capable of distinguishing HDV infection from HBV monoinfection, as well as to explore their discriminative potential. Materials and methods: This exploratory study employed untargeted metabolomic and lipidomic approaches based on high-resolution liquid chromatography–mass spectrometry (LC–MS) and gas chromatography–mass spectrometry (GC–MS), respectively. Residual anonymized serum samples from individuals with confirmed HDV infection and HBV-monoinfected controls from the Brazilian Amazon were provided by the Central Laboratory of Public Health of Acre and analyzed. Exploratory analyses were performed, including principal component analysis (PCA), as well as volcano plots and heatmaps to identify differentially abundant features. Predictive modeling using supervised machine learning algorithms was applied to evaluate discriminative performance. Results: Metabolomic analysis identified six metabolites significantly altered in HDV infection, predominantly related to lipid and phospholipid metabolism. Linoleic acid, heptadecanoic acid, 3-hydroxyicosanoic acid, pregnanolone, and choline showed higher abundance, whereas LysoPC(18:0/0:0) showed lower abundance in HDV-positive serum samples. Machine learning models demonstrated good discriminative performance, with Gradient Boosting achieving an area under the curve (AUC) of 0.943, with sensitivity and specificity of 86%. In contrast, lipidomic analysis revealed four lipid species with significantly lower abundance in HDV-positive samples, particularly cholesterol-derived compounds. Random Forest showed the best performance in this dataset, with an AUC of 0.854, sensitivity of 84.8%, and specificity of 100%. In both approaches, model interpretability, assessed using Shapley additive explanations (SHAP) and permutation-based feature importance, identified the same metabolites and lipids as the main contributors to model performance. Conclusions: HDV infection is associated with distinct metabolomic and lipidomic alterations in the context of HBV infection, suggesting a disruption of metabolic homeostasis, possibly associated with the severity of liver injury. These findings provide preliminary evidence supporting the use of metabolomic and lipidomic signatures, integrated with artificial intelligence analyses, for biomarker investigation, with potential applications in improving diagnosis and in characterizing alterations associated with hepatitis D. Further studies with larger and longitudinal cohorts are required to validate these findings.

Padrões crononutricionais e suas associações com desfechos metabólicos: resultados do National Health and Nutrition Examination Survey 2003–2018

2026-07-28T06:21:57Z

Title: Padrões crononutricionais e suas associações com desfechos metabólicos: resultados do National Health and Nutrition Examination Survey 2003–2018 Abstract: Introduction: Fasting duration has been widely investigated in relation to metabolism, weight loss, and chronic diseases. However, population-based studies describing its distribution and variation across sociodemographic subgroups remain limited. In addition, the timing and regularity of food intake influence circadian rhythms and metabolism and have been associated with various health outcomes such as obesity and metabolic syndrome. Long-term population based evidence integrating fasting patterns and eating timing remains scarce. Objectives: : To describe fasting patterns over a 16-year period among adults and elderly according to sociodemographic characteristics (manuscript 1). The second objective was to evaluate the association between chrononutrition patterns, defined by the timing of the first and last eating episodes, and metabolic outcomes in adults and elderly (manuscript 2). Materials and Methods: A total of 32,053 (manuscript 1) and 7,895 participants (manuscript 2) from eight cycles of the National Health and Nutrition Examination Survey (NHANES) (2003-2018) were analyzed. Information on fasting duration and eating timing was obtained from two 24-hour dietary recalls. The first eating episode was defined as the first intake of energy-containing foods or beverages recorded after 05:00, and the last eating episode corresponded to the final caloric intake of the day. Fasting patterns were defined as the interval between the last and first eating episodes, including fasting duration, fasting midpoint, and night fasting duration (18:00 6:00). Additional chrononutrition variables included eating duration, eating midpoint, timing of the first and last eating episodes, number of eating occasions, and total energy intake (manuscript 1). For manuscript 2, a chrononutrition pattern was defined based on the population median timing of the first and last eating episodes, categorized into earlier and later intake patterns. Associations were assessed using linear, logistic, and multinomial regression models adjusted for potential confounders in both manuscripts. In manuscript 2, Poisson regression was used to examine the association between chrononutrition patterns and metabolic outcomes, including fasting glucose, triglycerides, HDL cholesterol, obesity, abdominal obesity, and metabolic syndrome. Results: Fasting patterns differed across sociodemographic subgroups (p < 0.001), with later patterns more common among younger adults and individuals with lower educational attainment and income, and earlier patterns among elderly individuals. Differences in fasting duration and night fasting duration (18:00-6:00) were also observed across subgroups (p < 0.001), and findings from stratified analyses were consistent with those from the overall sample. Over the 16-year period, modest changes in fasting patterns were observed, including slight increases in night fasting duration (18:00–6:00) (p = 0.026), earlier timing of the last eating episode (p = 0.048), fewer eating occasions (p = 0.028), and lower total energy intake (p = 0.003) (manuscript 1). In manuscript 2, later eating patterns were associated with a higher prevalence of elevated triglycerides (PR: 1.23; 95% CI: 1.05-1.46) and elevated fasting glucose (PR: 1.13; 95% CI: 1.03-1.24; PR: 1.16; 95% CI: 1.05-1.28), compared with earlier eating patterns. Conclusion: Later fasting patterns were more common among younger adults and individuals with lower educational attainment and income, whereas earlier patterns were more frequent among elderly. Over time, only modest changes were observed in fasting patterns and other chrononutrition variables (manuscript 1). Additionally, later eating patterns were associated with worse metabolic outcomes (manuscript 2). These findings contribute to the understanding of fasting patterns across population subgroups and highlight the role of eating timing as a relevant factor in the understanding and potential prevention of metabolic disorders at the population level.

Associação entre o uso de clorexidina ou cetilpiridínio oral para prevenção de pneumonia associada à ventilação e a ocorrência de lesão pulmonar aguda em pacientes vítimas de traumatismo cranioencefálico: um ensaio clínico randomizado

2026-03-25T06:21:13Z

Title: Associação entre o uso de clorexidina ou cetilpiridínio oral para prevenção de pneumonia associada à ventilação e a ocorrência de lesão pulmonar aguda em pacientes vítimas de traumatismo cranioencefálico: um ensaio clínico randomizado Abstract: Introduction: Oral hygiene for critically ill patients on mechanical ventilation (MV) is an important strategy for preventing ventilator-associated pneumonia (VAP), and worldwide, the use of chlorhexidine in this procedure has been recommended and disseminated as routine. However, meta-analyses of double-blind randomized clinical trials have reported an association between the use of chlorhexidine in oral hygiene and increased mortality, and no reduction in VAP rates. The mechanism suggested to explain this increase in mortality is the occurrence of acute lung injury, since chlorhexidine is an acidic substance and, when aspirated, could cause direct pulmonary toxicity. Objectives: To evaluate whether there is an association between the use of chlorhexidine (CHX) in the oral hygiene of critically ill patients on mechanical ventilation and the occurrence of ALI, and whether cetylpyridinium chloride (CCP) is a safe option. Methods: This study is a randomized controlled clinical trial, registered under number RBR-7p6568 in the Brazilian Registry of Clinical Trials. The experimental protocols were approved by the local ethics committee and comply with the CONSORT (CONsolidated Standards of Reporting Trials) guidelines. Of the 59 eligible patients, 34 consented and were randomly allocated to three different groups: (A) oral hygiene with 0.12% chlorhexidine digluconate; (B) 0.075% cetylpyridinium chloride; (C) sterile water. The primary outcome was the occurrence of acute lung injury. Secondary outcomes were all-cause mortality, duration of mechanical ventilation, length of stay in the Intensive Care Unit (ICU), ICU-acquired infections, and antimicrobial resistance. The collected data were pooled and compared. Results: The use of chlorhexidine for oral hygiene in critically ill patients on mechanical ventilation showed a non-statistically significant association with an increased occurrence of acute lung injury and ICU-acquired infections. Statistical analysis showed no differences in prevalence percentages between groups for any variable, applying the Z-test of proportions with Bonferroni correction. In addition, the patients’ daily P/F ratio was collected for 14 days, and this data was analyzed using a Mixed Linear Model, in which no statistically significant differences were observed between the three groups in the daily P/F values throughout the follow-up period. Discussion: Considering that international guidelines have modified their recent recommendations and no longer 11 recommend chlorhexidine for oral hygiene in all critically ill patients, it is imperative to evaluate alternatives to chlorhexidine. In this study, the results showed no evidence of harm with the use of CCP, corroborating the fact that, unlike CHX, it is not an acidic substance. Conclusion: In institutions whose protocols guide the use of oral chlorhexidine only when specifically prescribed, CCP remains a possible alternative. Further investigations will be necessary to assess whether cetylpyridinium chloride in oral hygiene is a safe and effective strategy for preventing VAP and could, therefore, be recommended by guidelines for routine use in all critically ill patients on mechanical ventilation.

Investigação de soro e saliva por espectroscopia ATR-FTIR e avaliação de biomarcadores inflamatórios sistêmicos como estratégia de análise do câncer de mama

2026-02-10T06:30:19Z

Title: Investigação de soro e saliva por espectroscopia ATR-FTIR e avaliação de biomarcadores inflamatórios sistêmicos como estratégia de análise do câncer de mama Abstract: Introduction: Breast cancer is the most common malignant neoplasm among women worldwide and represents a significant public health challenge due to its molecular heterogeneity and prognostic impact. Therefore, the search for non-invasive and cost-effective methods of diagnosis and prognostic stratification becomes essential. Objective: To evaluate the clinical applicability of complementary approaches for the diagnosis and prognosis of breast cancer, investigating the usefulness of profiles obtained from biological fluids and systemic inflammatory and immunological biomarkers, as well as their correlations with clinicopathological characteristics and overall survival of women with breast cancer, including advanced cases. Materials and methods: In the first article, a cross-sectional study was conducted involving 73 participants: 31 with breast cancer, 18 with benign breast disease, and 24 healthy controls. Serum and saliva samples were analyzed by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), and spectral differences between groups were statistically evaluated. In the second article, a prospective study was conducted with 33 patients with advanced breast cancer followed in a palliative care program in Brazil between 2021 and 2024. Systemic inflammatory biomarkers were quantified by blood count and enzyme-linked immunosorbent assay (ELISA), and correlated with overall survival using Kaplan-Meier analyses and Cox regression models. Results: In the first article, the intragroup spectral analysis between breast cancer and benign breast disease, serum spectra showed no statistical differences. In saliva, only the peak at 2930 cm⁻¹, associated with C–H stretching vibration of lipids, differentiated breast cancer from benign breast disease (p = 0.0391). In the comparison between breast cancer and healthy controls, serum showed a significant difference at 1295 cm⁻¹ (related to nucleic acid cytokines). Saliva showed significant differences at 1241 cm⁻¹ (nucleic acid phosphate), 1541 cm⁻¹ and 1644 cm⁻¹ (protein amides II and I), and 2930 cm⁻¹ (lipids). In the intergroup analysis, comparing breast cancer, benign breast disease, and healthy controls, it was shown that the biochemical components present in serum and saliva, including lipids, nucleic acids, proteins, and carbohydrates, presented distinct absorbance patterns according to the type of biological fluid analyzed. The 2930 cm⁻¹ peak, related to C–H stretching of lipids in saliva, was able to differentiate the three groups studied. In the second article, the elevated levels of interleukin-1BETA (IL-1BETA) (> 76.03 pg/mL) were associated with worse overall survival (p = 0.018), increasing the risk of death by 8.84 times; and elevated levels of interleukin-10 (IL-10) (> 24.21 pg/mL) were also associated with worse overall survival (p = 0.046), increasing the risk of death by 7.17 times. Red blood cell distribution width (RDW), RDW/platelet ratio (RPR), neutrophil/lymphocyte ratio (N/L), lymphocyte/monocyte ratio (L/M), and interleukin-6 (IL-6) did not show a significant association with prognosis. Conclusions: The results demonstrate that ATR-FTIR spectroscopy is a promising tool for detecting breast cancer from saliva samples, offering advantages such as speed, reproducibility, and non-invasiveness. In parallel, the cytokines IL-1BETA and IL-10 emerge as relevant prognostic biomarkers in advanced disease, reflecting the interaction between systemic inflammation and tumor progression. The integration of these diagnostic and prognostic approaches in the clinical management of breast cancer can contribute to the development of personalized and accessible strategies.