An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter.

Background: Dietary composition can modify gene expression, favoring the development of chronic diseases via epigenetic mechanisms. Objective: Our study aimed to investigate the relationship between dietary patterns and NR3C1 gene methylation in users of the Brazilian Public Unified Health System (SUS). Methods: We recruited 250 adult volunteers and evaluated their socioeconomic status, psychosocial characteristics, lifestyle, and anthropometrics. Peripheral blood was collected and evaluated for cortisol levels, glycemia, lipid profile, and insulin resistance; methylation of CpGs 40-47 of the 1F region of the NR3C1 gene was also measured. Factors associated with degree of methylation were evaluated using generalized linear models (p < 0.05). Lifestyle variables and health variables were included as confounding factors. Results: The findings of our cross-sectional study indicated an association between NR3C1 DNA methylation and intake of processed foods. We also observed relevant associations of average NR3C1 DNA across the segment analyzed, methylation in component 1 (40-43), and methylation in component 2 (44-47) with a pattern of consumption of industrialized products in relation to BMI, serum cortisol levels, and lipid profile. These results may indicate a relationship between methylation and metabolic changes related to the stress response. Conclusion: These findings suggest an association of methylation and metabolic alterations with stress response. In addition, the present study highlights the significant role of diet quality as a stress-inducing factor that influences NR3C1 methylation. This relationship is further linked to changes in psychosocial factors, lifestyle choices, and cardiometabolic variables, including glucose levels, insulin resistance, and hyperlipidemia.

Psychotropic drug use and suggestive depression symptoms associated with NR3C1 DNA methylation / Uso de drogas psicotrópicas e sintomas sugestivos de depressão associados à metilação do DNA do NR3C1

Introduction: Psychiatric disorders have become a global problem that leads millions of people to use psychotropic medications, especially benzodiazepines. The effects of these substances are widely known regarding tolerance and chemical dependence, however, from epigenetics perspective, there are still little known.Objective: To evaluate the association between psychotropic drug use, NR3C1 gene methylation and its relation with symptoms suggestive of depression in adult individuals assisted in the public health system.Methods: 385 adult volunteers (20-59 years) users of the Brazilian Unified Health System were recruited to evaluate socioeconomic, health, lifestyle conditions in a cross sectional study. BDI-II evaluated symptoms suggestive of depression and pyrosequencing evaluated NR3C1 DNA methylation. Bivariate and multivariate Poisson regression model with robust variance (p < 0.05) evaluated the association between psychotropic drug use and NR3C1 gene methylation.Results: Specific depressive symptoms such as irritability, insomnia and fatigability were associated with psychotropic drug use. Symptoms of past failure, indecision and loss of appetite were associated with hypermethylation patterns in CpGs 40 to 47 of NR3C1 gene. Moreover, psychotropic drug use is associated with 50% reduction in NR3C1 gene methylation, through model adjusted with socioeconomic, health and lifestyle confounding variables.Conclusions: Psychotropic drug use and depressive symptoms was associated with changes in NR3C1 DNA methylation. In this context, epigenetic modification resulting from psychotropic drug use and depressive symptoms could be considered, mainly in population studies with epigenetic evaluation, where these factors may be influencing the findings of future studies.

Introdução: os distúrbios psiquiátricos tornaram-se um problema global que leva milhões de pessoas ao uso de medicamentos psicotrópicos. Os efeitos dessas substâncias são amplamente conhecidos quanto à tolerância e dependência química, porém, do ponto de vista epigenético, ainda são pouco conhecidos.Objetivos: avaliar a associação entre o uso de drogas psicotrópicas, metilação do gene NR3C1 e sua relação com sintomas sugestivos de depressão em indivíduos entre 20 a 59 anos usuários da rede pública de saúde.Método: 385 voluntários de 20-59 anos, usuários do Sistema Único de Saúde brasileiro foram recrutados para avaliação das condições socioeconômicas, de saúde e de estilo de vida em estudo transversal. O BDI-II avaliou sintomas sugestivos de depressão e o pirosequenciamento avaliou a metilação do DNA de NR3C1. Modelo de regressão de Poisson bivariado e multivariado com variância robusta (p < 0,05) avaliou a associação entre o uso de drogas psicotrópicas e metilação do gene NR3C1.Resultados: sintomas depressivos específicos como irritabilidade, insônia e fadiga foram associados ao uso de medicamentos psicotrópicos. Sintomas de fracasso passado, indecisão e perda de apetite foram associados a padrões de hipermetilação nos CpGs 40 a 47 do gene NR3C1. Além disso, o uso de psicofármacos está associado à redução de 50% na metilação do gene NR3C1, por meio de modelo ajustado com variáveis de confusão socioeconômicas, de saúde e estilo de vida.Conclusão: o uso de drogas psicotrópicas e sintomas específicos depressivos foram associados a alterações na metilação do DNA de NR3C1.

Epigenetic alteration of BDNF gene, social and health status as predictors of food and nutrition insecurity among familiar coffee farmers / Alteração epigenética no gene BDNF, status social e de saúde como preditores da insegurança alimentar e nutricional em cafeicultores familiares

ntroduction: state of Food and Nutritional Security (FNS) is one that should guarantee the right of permanent access to quality food and in sufficient quantity without prejudicing access to other basic rights. In Brazil, rural family farming establishments represent 84.4% of total agricultural establishments and contribute to more than 70% of all food consumed by Brazilians. In this context, the production of the coffee commodity stands out. However, despite being food producers, they do not earn a good income. Slow economic activity can lead to loss of wages and income, illness, as well as food insecurity (FNiS). In addition, the molecular effects of FNiS are poorly studied, especially epigenetic.Objective: the objective of the present study is to analyze the association between Brain-Derived Neurotrophic Factor (BDNF) DNA methylation and socio demographic, lifestyle, and epigenetic factors, among coffee farmers in the Caparaó zone, in Espirito Santo, Southeast Brazil.Methods: the study was carried out in 22 randomly selected coffee producing communities in Zona Caparaó, an area that produces coffee of recognized quality. A total of 570 coffee farming households, 18 to 60 years of age, were included in the study by answering a questionnaire about socioeconomic characteristics, land use and ownership, behavior, health, and working conditions. FNiS evaluation was carried out using the Brazilian Food Insecurity Scale. BDNF exon I methylation was examined by methylation-specific PCR. Body mass index and biochemical analyses were performed. Logistic regression models were used to verify factors associated with FNiS (p<0.05). Data were analyzed using the Stata® statistical software package version 14.Results: the FNiS prevalence found was 23.68%. In multivariable logistic regression, the occurrence of FNiS was associated with hypermethylation of exon I of the BDNF promoter exon I [ORa = 5.03 (95% (1.98, 12.82)] when compared to the unmethylated gene. Moreover, FNiS was associated with excessive workload [ORa = 3.36 (1.23, 9.22)], possession of less land (hectares) [ORa = 0.77 (0.67, 0.90)] and greater number symptoms and / or illnesses in real life [ORa = 1.12 (1.04.1.20)].Conclusion: there is a high prevalence of Food Insecurity in the studied region. This phenomenon was associated with epigenetic factors (BDNF methylation), excessive workload, small land ownership and a greater number of diseases / symptoms. Food insecurity is a psychosocial stressor that can lead to epigenetic changes in the BDNF gene, responsible for regulating cognitive functions, neuronal survival and involved in the genesis of psychiatric diseases.

Introdução: o Estado de Segurança Alimentar e Nutricional (SAN) é aquele que deve garantir o direito de acesso permanente à alimentação de qualidade e em quantidade suficiente sem prejudicar o acesso a outros direitos básicos. No Brasil, os estabelecimentos de agricultura familiar rural representam 84,4% do total de estabelecimentos agropecuários e contribuem com mais de 70% de todos os alimentos consumidos pelos brasileiros. Nesse contexto, destaca-se a produção da commodity café. No entanto, apesar de serem produtores de alimentos, não auferem bons rendimentos. A lenta atividade econômica pode levar à perda de salários e renda, doenças e insegurança alimentar (INSAN). Além disso, os efeitos moleculares da INSAN são pouco estudados, sobretudo epigenéticos.Objetivos: o objetivo do presente estudo é analisar a associação entre a metilação do promotor do BDNF e a INSAN e a associação da INSAN com fatores sociodemográficos, de estilo de vida e epigenéticos, em cafeicultores da zona do Caparaó, no Espírito Santo, Sudeste do Brasil.Método: o estudo foi realizado em 22 comunidades cafeeiras selecionadas aleatoriamente na Zona do Caparaó, área que produz café de reconhecida qualidade. Um total de 570 famílias de cafeicultores, entre 18 a 60 anos, foram incluídos no estudo e responderam a um questionário sobre características socioeconômicas, uso e posse da terra, hábitos de vida, saúde e condições de trabalho. A avaliação da INSAN foi realizada por meio da Escala Brasileira de Insegurança Alimentar. A metilação do éxon I do BDNF foi examinada por PCR específica para metilação. Índice de massa corporal e análises bioquímicas foram realizadas. Modelos de regressão logística foram utilizados para verificar os fatores associados à INSAN (p<0,05). Os dados foram analisados usando o software estatístico Stata® versão 14.Resultados: a prevalência de INSAN encontrada foi de 23,68%. Na regressão logística multivariada, a ocorrência de INSAN foi associada a hipermetilação do éxon I do promotor do gene BDNF [ORa = 5,03 (95% (1,98, 12,82)] quando comparado ao gene não metilado. Além disso, a INSAN foi associada a carga de trabalho excessiva [ORa = 3,36 (1,23, 9,22)], posse de menos hectares de terra [ORa = 0,77 (0,67, 0,90)] e maior número de sintomas e/ou doenças da vida real [ORa = 1,12 (1.04.1.20)].Conclusão: o estudo mostrou uma alta prevalência de Insegurança Alimentar na região analisada. Esse fenômeno foi associado a fatores epigenéticos (metilação do gene BDNF), carga horária excessiva, pequena propriedade de terra e maior número de doenças/sintomas. A INSAN pode ser um estressor capaz de promover alterações epigenéticas no gene BDNF, importante gene regulador da cognição, crescimento e sobrevivência neuronal e envolvido com doenças psiquiátricas.

Chlorine, chromium, proteins of oxidative stress and DNA repair pathways are related to prognosis in oral cancer.

The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.

PAI-1 expression in intratumoral inflammatory infiltrate contributes to lymph node metastasis in oral cancer: A cross-sectional study.

INTRODUCTION: Immune cells contribute with mediators in the protein expression profile of the tumor microenvironment. Levels of plasminogen activator inhibitor-1 (PAI-1) are elevated in non-malignant inflammatory conditions; however, the association between PAI-1 expression and inflammation remains uncertain in oral squamous cell carcinoma (OSCC). This study aimed to investigate PAI-1 expression in mononuclear inflammatory cell infiltrate in OSCC and its role as a prognostic marker. METHODS: Samples were collected from patients with OSCC, treated surgically, and followed for 24 months after the procedure. Thirty-nine tumoral tissue were analyzed using immunohistochemistry. Correlation between protein expression, clinicopathological parameters, and the prognosis was investigated. RESULTS: Positive PAI-1 expression in mononuclear inflammatory cell infiltrate was significantly associated with lymph node status (p = 0.009) and with the cytoplasmic expression of vascular endothelial growth factor A (VEGFA) (p = 0.028). Multivariate analysis revealed weak PAI-1 expression as an independent marker for lymph node metastases, with approximately 8-fold increased risk compared to strong expression (OR = 8.60; CI = 1.54-48.08; p = 0.014). CONCLUSION: Our results suggest that the strong PAI-1 expression in intratumoral inflammatory infiltrate is an indicator of a better prognosis for patients diagnosed with oral squamous cell carcinoma.

Food and nutritional insecurity is associated with depressive symptoms mediated by NR3C1 gene promoter 1F methylation.

The aim of this study was to investigate socioeconomic stressors predictive of depressive symptoms and possible epigenetic changes in the glucocorticoid receptor - NR3C1-1F - an encoding gene involved in depressive symptoms. A total of 321 adult volunteers from southeastern Brazil were recruited to evaluate depressive symptoms, socio-demographic and economic factors, including food and nutritional security (FNS) or insecurity (FNiS) status, and NR3C1-1F region methylation by pyrosequencing. Depressive symptom determinants were investigated using a Poisson regression model with robust variance. Mann-Whitney tests and structural mediation equation models were used to evaluate the relationship between NR3C1 DNA methylation, FNiS, and depressive symptoms. Multivariate Poisson regression with robust variance adjusted for sex and FNiS and NR3C1-1F region methylation predicted risk factors for depressive symptoms. Mediation analysis revealed that NR3C1-1F region methylation mediated the relationship between FNiS exposure and depressive symptoms as an outcome, and depressive volunteers and FNiS individuals exhibited a significant increase in NR3C1 methylation when compared to healthy individuals and FNS volunteers, respectively. Therefore, we suggest that stress caused by FNiS may lead to depressive symptoms and that NR3C1-1F DNA methylation can act as a mediator of both FNiS and depressive symptoms.

Risk factors for survival after head and neck cancer: a cohort study in the south of Espirito Santo state

Introduction: Head and check squamous cell carcinomas (HNSCC) affects the Brazilian population with a high incidence and usually has a poor prognosis. Objective: To evaluate the risk factors for survival of patients diagnosed with HNSCC and investigate the influence of epidemiological and clinical factors on the prognostic of HNSCC in southeastern Brazil. Materials and Methods: Clinical records of 211 patients with head and neck squamous cell carcinomas diagnosed and treated between 2010 and 2018 at a reference hospital for oncology, were selected. Clinical and pathological characteristics at diagnosis and for 5 years follow up were collected. The Kaplan-Meier Curve with the Log-Rank test assessed survival, and forward stepwise multivariate logistic regression model was performed to determine the factors affecting HNSCC survival. Results: The 5-year overall survival was 30.0%. Laryngeal cancer was the most prevalent (34.1%), followed by oropharynx (33.6%) and oral cavity (24.2%). About 64% of patients had locally advanced tumors (T3 and T4) and 75.4% of the patients were diagnosed as being in the advanced clinical stages (III and IV). In the multivariate analysis, the locally advanced tumors (OR=2.748; 95%CI:1.310- 5.765), palliative chemotherapy (OR=15.757; 95%CI:5.868-42.309) and metastasis during oncological follow-up (OR=11.602; 95%CI:1.380-97.507) were associated with a poor prognosis. Conclusion: The survival rate was considered low when compared with the literature. Locally advanced tumors, palliative chemotherapy, and the appearance of metastases during follow-up were considered the most important risk factors associated with a low HNSCC survival.

Introdução: O carcinoma de células escamosas (CCE) de cabeça e pescoço possui alta incidência na população brasileira e normalmente está associado a um prognóstico desfavorável. Objetivo: Avaliar os fatores de risco para sobrevida de pacientes diagnosticados com CCE de cabeça e pescoço e investigar a influência de fatores clínicoepidemiológicos no prognóstico do CCE. Materiais e Métodos: Foram selecionados prontuários de 211 pacientes com CCE de cabeça e pescoço diagnosticados e tratados entre 2010 e 2018 em um hospital de referência em oncologia. Foram coletadas as características clínico-patológicas no momento do diagnóstico e nos 5 anos de acompanhamento. A curva de Kaplan-Meier com o teste Log-Rank avaliou a sobrevivência e o modelo de regressão logística multivariada progressiva foram realizados para determinar os fatores que afetaram a sobrevivência do CCE. Resultados: A sobrevida global em 5 anos foi de 30,0%. O câncer de laringe foi o mais prevalente (34,1%), seguido de orofaringe (33,6%) e cavidade oral (24,2%). 64% dos pacientes apresentavam tumores localmente avançados (T3 e T4) e 75,4% dos pacientes foram diagnosticados em estádios clínicos avançados (III e IV). Na análise multivariada, os tumores localmente avançados (RC = 2,748; IC 95%: 1,310-5,765), quimioterapia paliativa (RC = 15,757; IC 95%: 5,868-42,309) e metástases durante o acompanhamento oncológico (RC = 11,602; IC 95%: 1,380-97,507) foram associados a um pior prognóstico. Conclusão: A taxa de sobrevida foi considerada baixa. Tumores localmente avançados, quimioterapia paliativa e aparecimento de metástases durante o seguimento foram considerados os fatores de risco mais importantes associados a uma baixa sobrevida.

Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation.

The NR3C1 glucocorticoid receptor (GR) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. NR3C1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. Previous studies have reported that stressful events are involved in NR3C1 gene methylation, suggesting that its regulation under environmental effects is complex. The present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to NR3C1 methylation in adults. This study included 386 individual users of the Brazilian Public Unified Health System (SUS), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. Data were correlated with NR3C1 methylation, determined using DNA pyrosequencing. The results showed that alcohol consumption, overweight, and high cortisol levels were related to NR3C1 demethylation, while depression was related to its methylation. Habits, lifestyle, and health status may influence NR3C1 gene regulation via methylation, revealing the complexity of environmental impacts on NR3C1 methylation.

Elemental characterization of oral cavity squamous cell carcinoma and its relationship with smoking, prognosis and survival.

Oral cancer squamous cell carcinoma (OCSCC) mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. Tobacco smoke contains hundreds of known toxic and carcinogenic molecules, and a few studies have sought to verify the relationship of such trace elements as risk or prognostic factors for head and neck cancer. We obtained 78 samples of tumor tissues from patients with OCSCC, and performed a qualitative elemental characterization using the micro X-Ray Fluorescence technique based on synchrotron radiation. We found the presence of magnesium, phosphorus, sulfur, chlorine, potassium, calcium, chromium, manganese, iron, zinc, cobalt, nickel, copper, arsenic and bromine in OCSCC samples. Magnesium, chlorine, chromium, manganese, nickel, arsenic and bromine are associated with smoking. We observed a significant association between relapse and chlorine and chromium. The presence of chlorine in the samples was an independent protective factor against relapse (OR = 0.105, CI = 0.01-0.63) and for best disease-free survival (HR = 0.194, CI = 0.04-0.87). Reporting for the first time in oral cancer, these results suggest a key relationship between smoking and the presence of certain elements. In addition, chlorine proved to be important in the context of patient prognosis and survival.

Factors Associated with Depressive Symptoms Among Rural Residents from Remote Areas.

This study aimed to investigate the risk factors for depressive symptoms among rural residents in Brazil. A representative sample of two hundred eighty-eight volunteers aged from 18 to 65 years was included and determining factors for high BDI-II score were investigated through a multivariate logistic model. Sadness, loss of pleasure, crying, worthlessness and loss of interest in sex are more likely to be observed in females, and risk factors to this high depression score among rural residents were shown to be: female gender, tobacco use, pesticide application, poor self-perceived health and presence of chronic disease. These data contribute to the knowledge of factors determining depressive symptoms among rural residents and may help to expand health policies to improve quality of rural life on these communities and others with similar characteristics.

Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association.

OBJECTIVE: The aim of this study was to verify determinant factors for depression and analyze the relationship between possible changes in HPA axis and depression, in this case NR3C1 DNA methylation and serum cortisol levels. METHODS: 349 adult volunteers were recruited to evaluate depression, socio-demographic, economic and lifestyle factors, serum cortisol levels and NR3C1 DNA methylation by pyrosequencing. Depression determinant factors were investigated using a Poisson regression model with robust variance (p < 0.05). RESULTS: Poisson regression with robust variance adjusted by gender, tobacco use, self-perceived stress, leisure activity, suicidal ideation, low cortisol levels and NR3C1 DNA methylation was performed and predicted risk factors for depression. Furthermore, depressive volunteers showed a significant increase in NR3C1 DNA methylation when compared to healthy volunteers. CONCLUSIONS: This findings provide a basis for understanding the role of HPA axis in depression, especially its regulation by NR3C1 DNA methylation. Furthermore, it emphasizes the stressful lifestyle risk factors (female, tobacco uso, self perceived stress, leisure activities absence and suicidal ideation) that can contribute to future research and the search for public health policies to improve quality of live, mental and general health.

Chemical composition of various plant extracts and their in vitro efficacy in control of Fasciola hepatica eggs / Composição química de vários extratos vegetais e sua eficácia in vitro no controle de ovos de Fasciola hepática

ABSTRACT: Fasciolosis has been diagnosed in cattle, goats, sheep and horses in southern and southeastern Brazil. Effective alternative treatments are the targets of study. One promising alternative is the use of plant extracts. The aim of this study was to perform phytochemical analysis of extracts of Eugenia uniflora L., Harpagophytum procumbens, Psidium guajava L. and Stryphnodendron adstringens, and to evaluate the in vitro efficacy of these extracts on ovicidal activity in Fasciola hepatica. Plant extracts were analyzed for phytochemical properties. F. hepatica eggs were collected directly from the gallbladders of animals diagnosed as positive for fasciolosis on post mortem examination. One hundred eggs were incubated with 3 ml of each extract at concentrations of 0.10%, 0.25% and 0.50%, albendazole 0.50% (positive control) or tap water (negative control). To determine anti larval efficacy of each plant extract, hatched eggs were counted and the averages were used. Phytochemical analysis revealed the presence of phenolic compounds, tannins and terpenes in most extracts. E. uniflora L. extract was 100% effective at 0.10%, H. procumbens was effective at 0.25% and P. guajava L. and S. adstringens extracts were 100% effective at all concentrations tested. Taken together, the data suggested that ovicidal activity in F. hepatica is due to the presence of these bioactive compounds.

RESUMO: A fasciolose tem sido diagnosticada em bovinos, caprinos, ovinos e equinos no sul e sudeste do Brasil, sendo que tratamentos alternativos mais eficazes são alvos de estudo. Umas das alternativas promissoras é o uso de extratos vegetais no controle dessa e outras enfermidades. O objetivo deste estudo foi realizar a análise fitoquímica dos extratos de Eugenia uniflora L., Harpagophytum procumbens, Psidium guajava L. e Stryphnodendron adstringens, além de avaliar a eficácia in vitro desses extratos na atividade ovicida em Fasciola hepatica. Os extratos vegetais foram obtidos e analisados para determinação fitoquímica. Ovos de F. hepatica foram coletados diretamente das vesículas biliares de animais diagnosticados como positivos para fasciolose no exame post mortem. Cem ovos foram incubados com três mililitros de cada extrato nas concentrações de 0,10%, 0,25% e 0,50%, de albendazol a 0,50% (controle positivo) e água de torneira (controle negativo). Para determinar a eficácia de cada extrato vegetal os ovos eclodidos foram contados, e a média utilizada para os cálculos de eficácia. A análise fitoquímica revelou a presença de compostos fenólicos, taninos e terpenos na maioria dos extratos. O extrato de E. uniflora L. apresentou eficácia de 100% na concentração de 0,10%, o de H. procumbens a 0,25% e os extratos de P. guajava L. e S. adstringens apresentaram 100% de eficácia em todas as concentrações testadas. Assim, sugere-se que a atividade ovicida em F. hepatica seja devido à presença desses compostos bioativos.

Microscopic alterations in Fasciola hepatica from sheep treated with albendazole / Alterações microscópicas em Fasciola hepatica de ovelhas tratadas com albendazol

Abstract Currently, albendazole is one of the most commonly used drugs because of its affordability. The objective was to evaluate the histopathology of Fasciola hepatica specimens. For this, the efficacy test was performed on sheep treated with albendazole at the dose recommended for F. hepatica, in which the helminths recovered at necropsy were counted and separated for histology. Spermatogenic cells from parasites recovered from treated and control sheep were examined by microscopy. The fecal egg-count reduction test revealed 97.06% efficacy of albendazole in the treatment of F. hepatica. Changes in testicular tubule cells started 48 hours after treatment and became evident within 72 hours, at which point it became difficult to identify cell types. Primary and secondary spermatogonia became increasingly rare and intercellular vacuolization was more evident. Signs of apoptosis, with pycnotic nuclei and evidence of keriorrexia were observed at all times. Cell debris was identified 96 hours after treatment. The results indicated that parasitic spermatogenesis was severely affected by albendazole and demonstrated the importance of the use of histopathology for the diagnosis of therapeutic efficacy in field strains.

Resumo Na atualidade, o albendazol é uma das drogas mais usadas devido à sua acessibilidade econômica. O objetivo foi avaliar a histopatologia dos espécimes de Fasciola hepatica. Para isso, foi realizado o teste de eficácia em ovinos tratados com albendazol na dose recomendada para Fasciola hepatica, no qual os helmintos recuperados em necropsia foram contabilizados e separados para histologia. As células espermatogênicas de parasitas recuperados de ovinos tratados e controle foram examinadas por microscopia. O teste de redução de ovos por grama de fezes revelou 97,06% de eficácia do albendazol no tratamento de F. hepatica. As alterações nas células dos túbulos testiculares iniciaram-se 48 horas após o tratamento e tornaram-se evidentes em 72 horas, altura em que tornou-se difícil identificar os tipos de células. As espermatogônias primárias e secundárias tornaram-se cada vez mais raras e a vacuolização intercelular foi mais evidente. Sinais de apoptose, com núcleos picnóticos e evidência de cariorrexia foram observados em todos os momentos. Os detritos celulares foram identificados 96 horas após o tratamento. Os resultados indicaram que a espermatogênese parasitária foi severamente afetada pelo albendazol e demonstrou a importância do uso da histopatologia para o diagnóstico de eficácia terapêutica em cepas de campo.

Microscopic alterations in Fasciola hepatica from sheep treated with albendazole.

Currently, albendazole is one of the most commonly used drugs because of its affordability. The objective was to evaluate the histopathology of Fasciola hepatica specimens. For this, the efficacy test was performed on sheep treated with albendazole at the dose recommended for F. hepatica, in which the helminths recovered at necropsy were counted and separated for histology. Spermatogenic cells from parasites recovered from treated and control sheep were examined by microscopy. The fecal egg-count reduction test revealed 97.06% efficacy of albendazole in the treatment of F. hepatica. Changes in testicular tubule cells started 48 hours after treatment and became evident within 72 hours, at which point it became difficult to identify cell types. Primary and secondary spermatogonia became increasingly rare and intercellular vacuolization was more evident. Signs of apoptosis, with pycnotic nuclei and evidence of keriorrexia were observed at all times. Cell debris was identified 96 hours after treatment. The results indicated that parasitic spermatogenesis was severely affected by albendazole and demonstrated the importance of the use of histopathology for the diagnosis of therapeutic efficacy in field strains.

Psychosocial stress and central adiposity: A Brazilian study with a representative sample of the public health system users.

OBJECTIVE: To assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil. METHODS: This cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (µg/dL), symptoms suggestive of depression using the Beck Depression Inventory-II ≥ 17 (yes/no), and altered blood pressure ≥ 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were made separately by rural and urban location. RESULTS: The prevalence of weight excess, by the classification of the Body Mass Index ≥ 25.0 kg/m2, was 68.3% and, by waist circumference, 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 ± 12.7 cm and 92.9 ± 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population (ß = -0.60; 95% CI = -1.09;-0.11) and altered blood pressure in the urban population (ß = 6.66; 95% CI = 2.14;11.18). This occurred both in the raw analysis and in the models adjusted for confounding factors. CONCLUSION: Central adiposity was inversely associated with cortisol in the rural population and directly associated with higher arterial blood pressure in the urban population, suggesting a local influence on how individuals react to stress.

JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma.

AIMS: Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. METHODS AND RESULTS: We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. CONCLUSION: JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.