Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer.

The treatment for locally advanced rectal carcinomas (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) and surgery, which results in pathological complete response (pCR) in up to 30% of patients. Since epigenetic changes may influence response to therapy, we aimed to identify DNA methylation markers predictive of pCR in LARC patients treated with nCRT. We used high-throughput DNA methylation analysis of 32 treatment-naïve LARC biopsies and five normal rectal tissues to explore the predictive value of differentially methylated (DM) CpGs. External validation was carried out with The Cancer Genome Atlas-Rectal Adenocarcinoma (TCGA-READ 99 cases). A classifier based on three-CpGs DM (linked to OBSL1, GPR1, and INSIG1 genes) was able to discriminate pCR from incomplete responders with high sensitivity and specificity. The methylation levels of the selected CpGs confirmed the predictive value of our classifier in 77 LARCs evaluated by bisulfite pyrosequencing. Evaluation of external datasets (TCGA-READ, GSE81006, GSE75546, and GSE39958) reproduced our results. As the three CpGs were mapped near to regulatory elements, we performed an integrative analysis in regions associated with predicted cis-regulatory elements. A positive and inverse correlation between DNA methylation and gene expression was found in two CpGs. We propose a novel predictive tool based on three CpGs potentially useful for pretreatment screening of LARC patients and guide the selection of treatment modality.

Pulmonary metastases in children: are we operating unnecessarily? / Metástases pulmonares em crianças: estamos operando desnecessariamente?

OBJECTIVE: to determine, in pediatric patients with malignant neoplasms, the characteristics of pulmonary nodules identified on computed tomography, as well as the possibility of differentiating benign lesions from metastases. METHODS: we conducted a retrospective study of patients submitted to pulmonary resections of nodules diagnosed as metastases in a period of seven years. We compared computed tomography and surgery findings, as well as results of anatomopathological examinations. RESULTS: we studied nine patients submitted to 11 surgical interventions. Among the studied variables, only nodule size greater than 12.5mm proved to be statistically significant to predict malignancy. CONCLUSION: among the tomographic characteristics of pulmonary nodules in children with malignant neoplasms, only the size of the lesion was a predictor of malignancy.

OBJETIVO: determinar, em pacientes pediátricos portadores de neoplasias malignas, as características de nódulos pulmonares identificados à tomografia computadorizada, capazes de diferenciar nódulos benignos de metástases. MÉTODOS: estudo retrospectivo de pacientes submetidos a ressecções pulmonares de nódulos diagnosticados como metástases em um período de sete anos. Achados de tomografia e da cirurgia, assim como resultados dos exames anatomopatológicos foram comparados. RESULTADOS: nove pacientes, submetidos a 11 intervenções cirúrgicas, foram estudados. Entre as variáveis estudadas, apenas o tamanho do nódulo, maior do que 12,5mm provou ser estatisticamente significante para predizer malignidade. CONCLUSÃO: esse estudo sugere que, entre as características tomográficas de nódulos pulmonares de crianças portadoras de neoplasias malignas, apenas o tamanho da lesão foi preditor de malignidade.

Metástases pulmonares em crianças: estamos operando desnecessariamente? / Pulmonary metastases in children: are we operating unnecessarily?

RESUMO Objetivo: determinar, em pacientes pediátricos portadores de neoplasias malignas, as características de nódulos pulmonares identificados à tomografia computadorizada, capazes de diferenciar nódulos benignos de metástases. Métodos: estudo retrospectivo de pacientes submetidos a ressecções pulmonares de nódulos diagnosticados como metástases em um período de sete anos. Achados de tomografia e da cirurgia, assim como resultados dos exames anatomopatológicos foram comparados. Resultados: nove pacientes, submetidos a 11 intervenções cirúrgicas, foram estudados. Entre as variáveis estudadas, apenas o tamanho do nódulo, maior do que 12,5mm provou ser estatisticamente significante para predizer malignidade. Conclusão: esse estudo sugere que, entre as características tomográficas de nódulos pulmonares de crianças portadoras de neoplasias malignas, apenas o tamanho da lesão foi preditor de malignidade.

ABSTRACT Objective: to determine, in pediatric patients with malignant neoplasms, the characteristics of pulmonary nodules identified on computed tomography, as well as the possibility of differentiating benign lesions from metastases. Methods: we conducted a retrospective study of patients submitted to pulmonary resections of nodules diagnosed as metastases in a period of seven years. We compared computed tomography and surgery findings, as well as results of anatomopathological examinations. Results: we studied nine patients submitted to 11 surgical interventions. Among the studied variables, only nodule size greater than 12.5mm proved to be statistically significant to predict malignancy. Conclusion: among the tomographic characteristics of pulmonary nodules in children with malignant neoplasms, only the size of the lesion was a predictor of malignancy.

Anti-nociceptive and anti-oedematogenic properties of the hydroethanolic extract of Sidastrum micranthum leaves in mice

Sidastrum micranthum (A. St.-Hil.) Fryxell, Malvaceae, grows in the northeastern region of Brazil, where the leaves of this species are traditionally used to treat coughs, bronchitis or asthma. Male Swiss mice (20-22 g) were tested in models of acute pain (acetic acid-induced abdominal writhing, tail flick and formalin test), oedema assessment test (paw oedema test) and model for evaluation of spontaneous motor performance (open field test). The hydroethanolic extract of S. micranthum was administered orally at doses of 50-500 mg/kg. In addition were administered water, vehicle, morphine 5.01 mg/kg (evaluation of pain and motor performance) and dexamethasone 2.25 mg/kg (evaluation of oedema formation). The extract showed a significant effect at all doses in the acetic acid-induced abdominal writhing test and at the second phase of the formalin test, while in the first phase of this test and in the paw oedema test only at the highest dose (500 mg/kg). In the formalin and paw oedema tests, the extract had a potentiation of the anti-nociceptive and anti-inflammatory effects by pretreatment with L-NAME and reduction of the effect by pretreatment with L-arginine. The extract was not toxic after oral administration (LD50 > 2000 mg/kg).

A influencia de fatores ambientais na qualidade de vida e na sintomatologia de criancas com rinite alergica / The impact of environmental factors on quality of life and symptoms of children with allergic rhinitis

A rinite alérgica é uma inflamação da mucosa nasal, induzida pela exposição a alérgenos, responsável por impacto negativo sobre a capacidade cognitiva dos afetados. OBJETIVO: Correlacionar a média da qualidade de vida de crianças e adolescentes com sintomas de rinite alérgica com a presença de fatores ambientais domiciliares relatados na literatura como desencadeantes das crises alérgicas. MÉTODO: Estudo de coorte histórica com corte transversal no qual foram convidadas a participar 120 crianças e adolescentes com manifestações clínicas de rinite alérgica, as quais foram divididas em dois grupos, de acordo com a quantidade de fatores ambientais inadequados em seus domicílios. Aplicou-se, então, o questionário PedsQL 4.0 para quantificação da qualidade de vida com posterior comparação entre os grupos. RESULTADOS: Não foi encontrada diferença significante (p > 0,05) na média dos escores do questionário PedsQL ao comparar a qualidade de vida dos participantes com a presença dos fatores ambientais inadequados avaliados no estudo, porém, notou-se maior incidência de manifestações alérgicas nas crianças com maior número desses fatores. CONCLUSÃO: Os fatores ambientais inadequados estudados não tiveram relação com a qualidade de vida dos pacientes. No entanto, a análise das moradias e sintomatologia dos mesmos sugere que o ambiente interferiu no aparecimento das manifestações alérgicas. .

Allergic rhinitis is an inflammation of the nasal mucosa caused by exposure to allergens, which impairs the cognitive capabilities of the affected. OBJECTIVE: To correlate the mean scores of quality of life of children and adolescents with symptoms of allergic rhinitis and the presence of household environmental factors described in the literature as allergy triggers. METHOD: This cross-sectional retrospective cohort study included 120 children and adolescents presenting clinical manifestations of allergic rhinitis. The subjects were divided into two groups based on the number of allergy-triggering environmental factors seen in their households. Scale PedsQL 4.0 was used to quantify quality of life and allow further comparisons between groups. RESULTS: No statistically significant differences (p > 0.05) were seen in the PedsQL mean scores when participant quality of life was analyzed vis-a-vis triggering environmental factors. However, the incidence of allergy manifestations was higher in children exposed to more environmental factors. CONCLUSION: The studied environmental factors were not correlated with patient quality of life. However, the analysis of patient households and symptoms indicates the environment played a role in the onset of allergy events. .