Synthesis and In Vitro and Silico Anti-inflammatory Activity of New Thiazolidinedione-quinoline Derivatives.

BACKGROUND: Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity. OBJECTIVE: Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade. METHODS: After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets. RESULTS: LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 µM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol. CONCLUSION: These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.

An Intestinal FXR Agonist Mitigates Dysbiosis, Intestinal Tight Junctions, and Inflammation in High-Fat Diet-Fed Mice.

SCOPE: To analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high-fat (HF) diet. METHODS AND RESULTS: Three-month-old C57Bl/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C + FEX, HF, and HF + FEX groups. FEX is administered (FEX-5 mg kg-1 ) via orogastric gavage for three weeks. Body mass (BM), glucose metabolism, qPCR 16S rRNA gene expression, and ileum gene expression, bile acids (BAs), tight junctions (TJs), and incretin are analyzed. FEX reduces BM and glucose intolerance, reduces plasma lipid concentrations and the Firmicutes/Bacteroidetes ratio, increases the Lactobacillus sp. and Prevotella sp. abundance, and reduces the Escherichia coli abundance. Consequently, the ileal gene expression of Fxr-Fgf15, Tgr5-Glp1, and Cldn-Ocldn-Zo1 is increased, and Tlr4-Il6-Il1beta is decreased. CONCLUSION: FEX stimulates intestinal FXR and improves dysbiosis, intestinal TJs, and the release of incretins, mitigating glucose intolerance and BM increases induced by an HF diet. However, FEX results in glucose intolerance, insulin resistance, and reduces intestinal TJs in a control group, thus demonstrating limitations to this dietary model.

Dieta mediterrânea para prevenção de doenças cardiovasculares: overview de revisões sistemáticas / Mediterranean diet for prevention of cardiovascular diseases: overview of systematic reviews

Contextualização: As doenças cardiovasculares (DCV) representam a principal causa de morte no Brasil e no mundo e a dieta mediterrânea (DM) surgiu como possibilidade de prevenção dessas doenças. Ela envolve o alto consumo de frutas, vegetais, frutos do mar, nozes, legumes, grãos e azeite, e ingestão moderada de vinho nas refeições, além de menor ingestão de carnes vermelhas e processadas, gordura saturada, doces e bebidas açucaradas. Objetivo: Avaliar a efetividade da DM para prevenção de DCV. Métodos: Trata-se de overview de revisões sistemáticas. Procedeu-se à busca por estudos que associavam a DM às DCV em quatro bases eletrônicas de dados: Cochrane - Central de Registros de Ensaios Clínicos - CENTRAL (2023), PubMed (1966-2023), Portal BVS (1982-2023) e EMBASE (1974-2023). Dois pesquisadores, independentemente extraíram os dados e avaliaram a qualidade dos estudos para a síntese. O desfecho primário de análise envolveu a prevenção de doença cardiovascular e a redução de mortalidade. Resultados: 5 revisões sistemáticas foram incluídas, totalizando 74 ensaios clínicos (n = 124.820) e 16 coortes prospectivas (n = 722.495). Discussão: Embora os estudos incluídos relatem benefícios favoráveis à DM para prevenção de DCV, as evidências são de baixa a moderada qualidade, diante da heterogeneidade e fragilidades metodológicas. Sugere-se a realização de novos estudos clínicos com padronização de relato dos resultados. Conclusão: Parece haver benefício da DM para prevenção de DCV, mas diante das evidências limitadas, há incertezas que tornam lícita a recomendação por novos ensaios clínicos com comparação a outras dietas, para maior robustez dos achados.

Saline extract of Portulaca elatior leaves with photoprotective and antioxidant activities does not show acute oral and dermal toxicity in mice.

The present study aimed to evaluate saline extracts from the leaves (LE) and stem (SE) of Portulaca elatior in relation to their phytochemical composition and photoprotective and antioxidant effects, as well as to evaluate the toxicity of the leaf extract. The extracts were characterized for protein concentration and phenol and flavonoid contents, as well as for thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) profiles. Total antioxidant capacity and DPPH and ABTS+ scavenging activities were determined. In the photoprotective activity assay, the sun protection factor (SPF) was calculated. The toxicity evaluation of LE included in vitro hemolytic assay and in vivo oral and dermal acute toxicity assays in Swiss mice. LE showed the highest protein, phenol, and flavonoid (8.79 mg/mL, 323.46 mg GAE/g, and 101.96 QE/g, respectively). TLC revealed the presence of flavonoids, reducing sugars, terpenes, and steroids in both extracts. In HPLC profiles, LE contained flavonoids, while SE contained flavonoids and ellagic tannins. The antioxidant activity assays showed the lowest IC50 values ​(34.15-413.3 µg/mL) for LE, which presented relevant SPF (> 6) at 50 and 100 µg/mL. LE demonstrated low hemolytic capacity, and no signs of intoxication were observed in mice treated orally or topically at 1000 mg/kg. However, at 2000 mg/kg, an increase in the mean corpuscular volume of erythrocytes and a reduction in lymphocytes were observed; animals treated topically with 2000 mg/kg displayed scratching behavior during the first hour of observation and showed edema and erythema that regressed after six days. In conclusion, LE did not present acute oral or dermal toxicity in Swiss mice at a dose of 1000 mg/kg and showed slight toxicity in animals treated with 2000 mg/kg. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00160-2.

DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development.

DNA methylation may be involved in the development of osteosarcomas. Osteosarcomas commonly arise during the bone growth and remodeling in puberty, making it plausible to infer the involvement of epigenetic alterations in their development. As a highly studied epigenetic mechanism, we investigated DNA methylation and related genetic variants in 28 primary osteosarcomas aiming to identify deregulated driver alterations. Methylation and genomic data were obtained using the Illumina HM450K beadchips and the TruSight One sequencing panel, respectively. Aberrant DNA methylation was spread throughout the osteosarcomas genomes. We identified 3146 differentially methylated CpGs comparing osteosarcomas and bone tissue samples, with high methylation heterogeneity, global hypomethylation and focal hypermethylation at CpG islands. Differentially methylated regions (DMR) were detected in 585 loci (319 hypomethylated and 266 hypermethylated), mapped to the promoter regions of 350 genes. These DMR genes were enriched for biological processes related to skeletal system morphogenesis, proliferation, inflammatory response, and signal transduction. Both methylation and expression data were validated in independent groups of cases. Six tumor suppressor genes harbored deletions or promoter hypermethylation (DLEC1, GJB2, HIC1, MIR149, PAX6, and WNT5A), and four oncogenes presented gains or hypomethylation (ASPSCR1, NOTCH4, PRDM16, and RUNX3). Our analysis also revealed hypomethylation at 6p22, a region that contains several histone genes. Copy-number changes in DNMT3B (gain) and TET1 (loss), as well as overexpression of DNMT3B in osteosarcomas provide a possible explanation for the observed phenotype of CpG island hypermethylation. While the detected open-sea hypomethylation likely contributes to the well-known osteosarcoma genomic instability, enriched CpG island hypermethylation suggests an underlying mechanism possibly driven by overexpression of DNMT3B likely resulting in silencing of tumor suppressors and DNA repair genes.

The patient generated-subjective global assessment (PG-SGA) and ECOG performance status are associated with mortality in patients hospitalized with breast cancer.

AIM: This study evaluated the association between risk of malnutrition and performance status, and mortality in hospitalized breast cancer patients. METHODS: Prospective cohort study with hospitalized breast cancer patients evaluated at a referral Cancer Center. The Risk of malnutrition was assessed by the Patient-Generated Subjective Global Assessment (PG-SGA) and performance status was determined using the Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS). Logistic regression was used to analyze the factors associated with death, using the odds ratio (OR) with a 95% confidence interval (CI) as an effect measure. RESULTS: A total of 195 woman were included, with a mean age of 56.3 (±12.6) years. Patients with an overall PG-SGA score ≥18 (OR: 2.11; 95% CI: 1.03-4.62) and ECOG PS ≥ 3 (OR: 3.34; 95% CI: 1.48-7.52) had a higher occurrence of death during hospitalization, regardless of age or disease stage. The concomitant presence of these two factors improved the accuracy of the association (OR: 5.32; 95% CI: 3.11-9.76) and showed good predictive accuracy (C-statistics: 0.77). CONCLUSION: Nutritional risk and poor performance status were associated with a higher occurrence of death in women with breast cancer. The use of these two indicators improves their predictive accuracy for mortality.

Immunoparalysis in critically ill children.

Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university-affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)-DR expression and tumour necrosis factor (TNF)-α and interleukin (IL)-6 production were measured by flow-cytometry at three time points (T1 = 1-2 days; T2 = 3-5 days; T3 = 6-8 days). Using the paediatric logistic organ dysfunction-2 score to assess initial disease severity, we established the optimal cut-off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA-DR ≤ 1758.5, area under the curve (AUC) = 0.775; and frequency of monocytes producing IL-6 ≤ 68.5%, AUC = 0.905) or in T3 (classical monocytes MFI of HLA-DR ≤ 2587.5, AUC = 0.675; and frequency of monocytes producing TNF-α ≤ 93.5%, AUC = 0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p = 0.011), vasoactive inotropic score (p = 0.014) and length of hospital stay (p = 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n = 5), patients showed higher percentages of non-classical monocytes (p = 0.004). No mortality was recorded. A reduction in classical monocytes HLA-DR expression with lower frequencies of monocytes producing TNF-α and IL-6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non-classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.

The relationship between serum fatty acids and depressive symptoms in obese adolescents.

Depression and obesity are highly prevalent and are considered inflammatory pathologies; in addition, they are also associated with dietary patterns including types of fatty acids (FA). Changes in the FA composition in the brain are determined by changes in the content and quality of dietary and serum FA. The aim of this study was to verify the relationships between serum-free FA, inflammatory processes and depressive symptoms in obese adolescents. This was a cross-sectional study that analysed a database composed of 138 post-pubertal adolescents. Data regarding the depressive symptoms, body composition, glucose metabolism, lipid profile, FA profile, leptin concentration, as well as adiponectin, IL-A, IL-6, IL-10, TNF-α, C-reactive protein and plasminogen activator inhibitor-1 levels of the subjects were collected. A total of 54·6 % of the adolescents presented with depressive symptoms, and there were positive correlations between depressive symptoms and serum saturated fatty acids (SFA) content, body fat, and inflammatory adipokines, such as leptin, IL-6, and the leptin/adiponectin ratio. Moreover, the content of n-3 polyunsaturated fatty acids (PUFA) was negatively correlated with depressive symptoms, suggesting that eicosatrienoic acid (C20:2n6) and dihomo-γ-linolenic acid (C20:3n-6) are independently associated with depressive symptom scores and can be critical predictors of poor mental health in humans. These results point to the relationship between SFA and depressive symptoms in obese adolescents. However, longitudinal studies are needed to confirm the causality between dietary SFA and depression in obese individuals.

Semaglutide (GLP-1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice.

Semaglutide (GLP-1 agonist) was approved for treating obesity. Although the effects on weight loss and metabolism are known, the responses of adipocytes to semaglutide are yet limited. C57BL/6 male mice (n = 20/group) were fed a control diet (C) or a high-fat (HF) diet for 16 weeks and then separated into four groups (n = 10/group) for an additional four weeks: C, C diet and semaglutide, HF, and HF diet and semaglutide. Epididymal white adipose tissue (eWAT) and subcutaneous white adipose tissue (sWAT) fat pads were studied with biochemistry, immunohistochemistry/fluorescence, stereology, and reverse transcription-quantitative polymerase chain reaction. In obese mice, semaglutide reduced the fat pad masses (eWAT, -55%; sWAT, -40%), plasmatic cytokines, and proinflammatory gene expressions: tumor necrosis factor-alpha (-60%); interleukin (IL)-6 (-55%); IL-1 beta (-40%); monocyte chemoattractant protein-1 (-90%); and leptin (-80%). Semaglutide also lessened endoplasmic reticulum (ER) stress genes of activating transcription factor-4 (-85%), CCAAT enhancer-binding protein homologous protein (-55%), and growth arrest and DNA damage-inducible gene 45 (-45%). The obese mice's adipocyte hypertrophy and macrophage infiltration were equally reduced by semaglutide. Semaglutide enhanced multiloculation and uncoupled protein 1 (UCP1) labeling in obese mice: peroxisome proliferator-activated receptor-alpha (+560%) and gamma (+150%), fibronectin type III domain-containing protein 5 (+215%), peroxisome proliferator-activated receptor-alpha coactivator (+110%), nuclear respiratory factor 1 (+260%), and mitochondrial transcription factor A (+120%). Semaglutide also increased thermogenetic gene expressions for the browning phenotype maintenance: beta-3 adrenergic receptor (+520%), PR domain containing 16 (+90%), and Ucp1 (+110%). In conclusion, semaglutide showed significant beneficial effects beyond weight loss, directly on fat pads and adipocytes of obese mice, remarkably anti-inflammatory, and reduced adipocyte size and ER stress. Besides, semaglutide activated adipocyte browning, improving UCP1, mitochondrial biogenesis, and thermogenic marker expressions help weight loss.

Effects of Acylhydrazone Derivatives on Experimental Pulmonary Inflammation by Chemical Sensitization.

BACKGROUND: Chronic lung diseases are characterized by airway inflammation and remodelling of the lung parenchyma that triggers considerable impairment of respiratory function. OBJECTIVE: In this study, two compounds belonging to the N-acylhydrazone class were evaluated, aiming to identify new therapeutic agents for pulmonary inflammatory diseases. MATERIALS AND METHODS: The acute toxicity of 2-cyano-N'-(3-ethoxy-4-hydroxybenzylidene)- acetohydrazide (JR-12) and N'-benzylidene-2-cyano-3-phenylacrylohydrazide (JR09-Bz) was evaluated. Afterwards, they were tested in models of ovalbumin (OVA)-induced allergic asthma and pleurisy, bleomycin-induced pulmonary fibrosis, in addition to mucolytic activity. RESULTS AND DISCUSSION: The compounds did not show toxicity at the dose of 2,000 mg/kg, and no animal died. On OVA-induced pleurisy, animals treated with JR-12 or JR09-Bz at a dose of 10 mg/kg (orally) showed significant inhibition of the leukocyte infiltrate in the bronchoalveolar lavage by 62.5% and 61.5%, respectively, compared to the control group. The compounds JR-12 and JR09-Bz were also active in blocking the allergic asthmatic response triggered by OVA, reducing the leukocyte infiltrate by 73.1% and 69.8%, respectively. Histopathological changes and mast cell migration in treated animals with JR-12 or JR09-Bz were similar to treatment with the reference drugs dexamethasone and montelukast. JR-12 and JR09-Bz also reversed airway remodeling in animals on the bleomycin-induced fibrosis model compared to the control group. Furthermore, it was observed that N-arylhydrazone derivatives showed expectorant and mucolytic activities, increasing mucus secretion by 45.6% and 63.8% for JR-12 and JR09-Bz, respectively. CONCLUSION: Together, the results show that JR-12 and JR09-Bz showed promising activity against airway inflammation, as well as low toxicity.

Gamete and embryo donation for research: what might shape the willingness to donate among gamete donors and recipients?

PURPOSE: Research using gametes and embryos donated by reproductive and third-party donors contributed to substantial, albeit contentious achievements. The views of gamete donors and recipients on donation for research and the underpinning role of attitudes towards research have been seldom explored and are yet to be incorporated into ethical, legal, and regulatory landscapes. From a cultural standpoint, this study adapts and explores psychometric properties of the Portuguese version of the Research Attitudes Questionnaire (RAQ), and analyzes the willingness of gamete donors and recipients to donate gametes and embryos for research and its association with sociodemographic, reproductive characteristics, and attitudes towards research. METHODS: Between July 2017 and June 2018, 71 donors and 165 recipients completed a self-administered questionnaire at the Portuguese Public Bank of Gametes. Willingness to donate and attitudes towards research were measured with a 5-point Likert scale. RAQ psychometric characteristics were explored. RESULTS: Two RAQ components were identified: "trustworthiness of research" and "critical perspective". Most participants were willing to donate gametes and embryos: donors more willing to donate gametes and male recipients more willing to donate gametes and embryos. Higher RAQ scores, indicating a more positive attitude towards research, were observed on the component "trustworthiness of research" among those willing to donate gametes and embryos and on the component "critical perspective" among those willing to donate embryos. CONCLUSION: These findings help foster inclusivity, diversity, and responsiveness of research and call for upstream engagement of male and female gamete donors and recipients, promoting a trustworthy, anticipatory, democratic, and people-centered approach to policies, regulations, and practices in human gamete and embryo research.

Enhancing untargeted metabolomics using metadata-based source annotation.

Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library. Applying this approach to food source data, we show that it increases MS/MS spectral usage 5.1-fold over conventional structural MS/MS library matches and allows empirical assessment of dietary patterns from untargeted data.

Empagliflozin Alleviates Left Ventricle Hypertrophy in High-Fat-Fed Mice by Modulating Renin Angiotensin Pathway.

Aims. The cardiobenefits of empagliflozin are multidimensional, and some mechanisms are still unclear. The aim of the present study was to evaluate the effect of treatment with empagliflozin on biometric parameters and gene expression in the local cardiac RAS, oxidative stress, and endoplasmic reticulum pathways in a mouse model. Main Methods. Forty male C57BL/6 mice were fed with control (C) or high-fat (HF) diets for 10 weeks. After that, the groups were redistributed according to the treatment with empagliflozin-CE or HFE. The empagliflozin was administered via food for 5 weeks (10 mg/kg/day). We performed biochemical analyses, blood pressure monitoring, oral glucose tolerance test, left ventricle (LV) stereology, RT-qPCR for genes related to classical and counterregulatory local RAS, oxidative stress, and endoplasmic reticulum stress. Key Findings. In comparison to HF, HFE decreased body mass and improved glucose intolerance and insulin resistance. The cardiac parameters were enhanced after treatment as expressed by decrease in plasma cholesterol, plasma uric acid, and systolic blood pressure. In addition, LV analysis showed that empagliflozin reduces cardiomyocyte area and LV thickness. The local RAS had less activity of the classical pathway and positive effects on the counterregulatory pathway. Empagliflozin treatment also decreased oxidative stress and endoplasmic reticulum stress-related genes. Significance. Our results suggests that empagliflozin modulates the local RAS pathway towards alleviation of oxidative stress and ER stress in the LV, which may be a route to its effects on improved cardiac remodeling.

Medical ethics when moving towards non-anonymous gamete donation: the views of donors and recipients.

Drawing on the views of donors and recipients about anonymity in a country that is experiencing a transition towards non-anonymous gamete donation mandated by the Constitutional Court, we explore how the intersection between rights-based approaches and an empirical framework enhances recommendations for ethical policy and healthcare. Between July 2017 and April 2018, 69 donors and 147 recipients, recruited at the Portuguese Public Bank of Gametes, participated in this cross-sectional study. Position towards anonymity was assessed through an open-ended question in a self-report questionnaire, which was subject to content analysis. Preference for an anonymous donation regime was mentioned by 82.6% of donors and 89.8% of recipients; and all those with children. Instead of the rights-based reasoning used by the Constitutional Court, donors highlighted concerns over future relationships and recipients focused on socioethical values linked with the safeguard of safety, privacy and confidentiality. The remaining participants advocated the choice between anonymity or non-anonymity (double-track policy), invoking respect for their autonomy. The complex, diverse ethical views and reasoning of donors and recipients expand a traditionally dichotomous discussion. Their perspectives challenge the transition towards non-anonymity and international guidelines, raising awareness to the need for their involvement in the design of policies to enable choice according to their values and preferences, and of psychosocial counselling responsive to their socioethical concerns and sensitive to their parental status. Empirical frameworks complement rights-based approaches to uphold justice, fairness and equal respect, and to incorporate utility, beneficence and non-maleficence in policymaking and healthcare in the transition towards non-anonymity.

New Trends in Biological Activities and Clinical Studies of Quinolinic Analogues: A Review.

The quinolinic ring, present in several molecules, possesses a great diversity of biological activities. Therefore, this ring is in the structural composition of several candidates of drugs in preclinical and clinical studies; thus, it is necessary to compile these results to facilitate the design of new drugs. For this reason, some of the activities of compounds are selected to examine in this review, such as antimalarial, antimicrobial, anticancer, anti-inflammatory, antidiabetic, anti-rheumatic, and antiviral activities. All publications of scientific articles chosen are dated between 2000 and 2020. In addition to presenting the structures of some natural and synthetic compounds with their activities, we have listed the clinical studies of phases III and IV on antimalarial drugs containing the quinoline nucleus and phase III clinical studies on hydroxychloroquine and chloroquine to assess their possible role in COVID-19. Finally, we have reviewed some of the mechanisms of action, as well as the side effects of some of the quinolinic derivatives.

Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). OBJECTIVE: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. METHODS: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. RESULTS: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics. CONCLUSION: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.

Situações de vulnerabilidades vivenciadas por adolescentes infratores: uma revisão integrativa / Situaciones de vulnerabilidades experimentadas por delincuentes: una revisión integrativa / Vulnerability situations experienced by adolescent offenders: an integrative review

Resumo Objetivo: analisar as situações de vulnerabilidade vivenciadas por adolescentes que praticam atos infracionais. Materiais e Métodos: trata-se de uma revisão integrativa de literatura, realizada nas bases de dados Scientific Eletronic Library Online (Scielo), Biblioteca Virtual em Saúde (BVS) e Medical Literature Analysis and Retrieval System Online (Medline), que resultou em 33 estudos incluídos, publicados entre os anos de 2009 a 2019, e, que após análise de conteúdo semântica, originou quatro categorias. Resultados: os resultados foram apresentados nas categorias: relações familiares conflituosas; envolvimento com álcool e drogas; situações sociodemográficas desfavoráveis; vulnerabilidade programática e a ausência do Estado. Conclusão: este estudo aponta como contribuição para a prática dos profissionais, sobretudo da atenção primária, estratégias para analisar as situações de vulnerabilidades que adolescentes infratores vivenciam, e assim, atuar na promoção da saúde, minimização dos agravos e auxílio para a reinserção social.

Resumen Objetivo: analizar las situaciones de vulnerabilidad que viven los adolescentes infractores. Materiales y métodos: se trata de una revisión integradora de la literatura, realizada en las bases de datos Scientific Electronic Electronic Library Online (Scielo), Virtual Health Library (BVS) y Medical Literature Analysis and Retrieval System Online (Medline), que resultó en 33 estudios incluidos, publicado entre los años 2009 a 2019, y que luego del análisis de contenido semántico, se originaron cuatro categorías. Resultados: los resultados se presentaron en las categorías: relaciones familiares conflictivas; implicación con alcohol y drogas; situaciones sociodemográficas desfavorables; vulnerabilidad programática y ausencia del Estado. Conclusión: este estudio señala, como aporte a la práctica de los profesionales, especialmente en atención primaria, estrategias para analizar las situaciones de vulnerabilidad que viven los adolescentes infractores, y así, actuar en la promoción de la salud, minimización de lesiones y asistencia para la reinserción en comunidad.

Abstract Objective: To analyze the situations of vulnerability experienced by adolescent offenders. Method: This is an integrative literature review carried out in the Scientific Electronic Library Online (Scielo), Virtual Health Library (VHL) and Medical Literature Analysis and Retrieval System Online (Medline) databases which resulted in 33 included studies, published between the years 2009 and 2019 and that, after analysis of semantic content, originated four categories. Results: The results were presented in the categories: conflicting family relationships; involvement with alcohol and drugs; unfavorable sociodemographic situations; programmatic vulnerability and the absence of the State. Conclusion: As a contribution to the practice of professionals, especially in primary care, this study points out strategies to analyze the situations of vulnerability that adolescent offenders experience, and thus, act in the promotion of health, minimization of injuries and assistance for social reintegration.