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    Existence of algebraic limit cycles for polynomial planar differential equations

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    Neste trabalho apresentaremos ciclos limite algébricos para sistemas quadráticos e cúbicos. Para sistemas quadráticos mostraremos todas as famílias de sistemas que possuem ciclos limite algébricos de grau 4 e algumas de grau 5 e 6. Concluiremos que todos estes sistemas possuem um único ciclo limite, neste caso o algébrico. Para estes resultados utilizaremos técnicas projetivas. Finalmente mostraremos que existem equações diferenciais polinomiais de grau arbitrário que possuem ciclos limite algébricos de grau 3.In this work we will present algebraic limit cycles for quadratic and cubic systems. For quadratic systems we will show all the family of systems that have algebraic limit cycles of degree 4 and some of degree 5 and 6. We will conclude that all these systems have a unique limit cycle, the algebraic one. For these results we will use projective techniques. Finally we will show that there are polynomial systems of differential equations of arbitrary degree that have algebraic limit cycles of degree 3

    Validez y fiabilidad del dietary sodium restriction questionnaire (DSRQ)

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    Introduction: The Dietary Sodium Restriction Questionnaire (DSRQ) was designed to assess attitudes and behaviors of patients with heart failure (HF) related to following a low-sodium diet. Recently, it has been translated and culturally adapted for use in Brazil. However, further validation of the instrument is required before it can be used in the management of patients with HF in Brazil. Objective: To test the reliability and validity of the Brazilian version of the DSRQ. Methods: Face and content validity were assessed by a panel of experts. Construct validity was tested using exploratory and confirmatory factor analysis. Reliability was tested using Cronbach’s alpha to assess the internal consistency of the instrument. Results: A total of 206 systolic HF outpatients were assessed (mean age, 60.4 ± 11.9 years). Face and content validity analysis showed equivalence between the Brazilian version and the original instrument. In the exploratory factor analysis, the principal component analysis (PCA) yielded four factors with eigenvalues greater than 1. Three models were tested in the confirmatory factor analysis, and the three-factor model resulting from the PCA showed the best fit, accounting for 49% of the variance. Alpha values obtained for the attitude/ subjective norm, perceived behavioral control, and dependent behavior subscales were 0.71, 0.67, and 0.79, respectively. Conclusions: Our results suggest that the final validated Brazilian version of the DSRQ is a valid and reliable tool for measuring attitudes and behaviors related to following a low-sodium diet in Brazilian patients with HF.Introducción: El Dietary Sodium Restriction Questionnaire (DSRQ) evalúa actitudes y comportamientos de pacientes con insuficiencia cardiaca (IC) relacionados con el cumplimiento de la restricción de sodio. Recientemente, ha sido traducido y adaptado culturalmente para uso en Brasil. No obstante, una validación adicional del instrumento se requiere para que pueda ser utilizado en el manejo de pacientes con IC en Brasil. Objetivo: Probar la fiabilidad y validez de la versión brasileña del DSRQ. Métodos: Validez aparente y de contenido fueron evaluados por un grupo de especialistas. Validez de constructo se evaluó mediante análisis factorial exploratoria y confirmatoria. La fiabilidad y consistencia interna del cuestionario fue evaluada mediante el coeficiente alfa de Cronbach. Resultados: Un total de 206 pacientes ambulatorios con IC fueron evaluados (edad media, 60,4 ± 11,9 años). Los resultados de la validez aparente y de contenido demostró la equivalencia entre la versión brasileña y de la versión original. En el análisis factorial exploratorio, el análisis de componentes principales (PCA) se obtuvieron cuatro factores con valores superiores a 1. Tres modelos fueron probados en el análisis factorial confirmatoria, y el modelo de tres factores resultantes del PCA mostró el mejor ajuste, representando 49% de la varianza. El alfa obtenido para las escalas de actitud/norma subjetiva, control de la conducta percibido y comportamiento dependiente fueron 0,71, 0,67 y 0,79, respectivamente. Conclusiones: Nuestros resultados sugieren que la versión brasileña del DSRQ es un instrumento válido y fiable para medir las actitudes y comportamientos relacionados con una dieta baja en sodio en pacientes brasileños con IC

    Resveratrol abrogates the Temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the Temozolomide-induced senescence in glioma cells

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    Background: Temozolomide (TMZ) is the most widely used drug to treat glioblastoma (GBM), which is the most common and aggressive primary tumor of the Central Nervous System and one of the hardest challenges in oncotherapy. TMZ is an alkylating agent that induces autophagy, apoptosis and senescence in GBM cells. However, therapy with TMZ increases survival after diagnosis only from 12 to 14.4 months, making the development of combined therapies to treat GBM fundamental. One candidate for GBM therapy is Resveratrol (Rsv), which has additive toxicity with TMZ in several glioma cells in vitro and in vivo. However, the mechanism of Rsv and TMZ additive toxicity, which is the aim of the present work, is not clear, especially concerning cell cycle dynamics and long term effects. Methods: Glioma cell lines were treated with Rsv and TMZ, alone or in combinations, and the induction and the role of autophagy, apoptosis, cell cycle dynamics, protein expression and phosphorylation status were measured. We further evaluated the long term senescence induction and clonogenic capacity. Results: As expected, temozolomide caused a G2 cell cycle arrest and extensive DNA damage response. Rsv did not reduced this response, even increasing pATM, pChk2 and gammaH2Ax levels, but abrogated the temozolomide-induced G2 arrest, increasing levels of cyclin B and pRb(S807/811) and reducing levels of pWee1 (S642) and pCdk1(Y15). This suggests a cellular state of forced passage through G2 checkpoint despite large DNA damage, a scenario that may produce mitotic catastrophe. Indeed, the proportion of cells with high nuclear irregularity increased from 6 to 26% in 48 h after cotreatment. At a long term, a reduction in clonogenic capacity was observed, accompanied by a large induction of senescence. Conclusion: The presence of Rsv forces cells treated with TMZ through mitosis leading to mitotic catastrophe and senescence, reducing the clonogenic capacity of glioma cells and increasing the chronic effects of temozolomide

    O polimorfismo rs1893217 (T/C) no gene PTPN2 não está associado com diabetes melito em indivíduos do Sul do Brasil

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    Objective: To evaluate the association of the PTPN2 rs1893217 polymorphism with T1DM and/ or its clinical and laboratory characteristics in a Caucasian population from Southern Brazil. Subjects and methods: Four hundred and eighty six patients with T1DM and 484 non-diabetic subjects were included in the study. Genotyping of the PTPN2 rs1893217 was performed by real-time PCR. Results: Genotype frequencies did not differ between T1DM patients and non-diabetic subjects (P = 0.265). The C allele was observed in 14.5% of the T1DM sample and 12.2% of the non-diabetic group (P = 0.152). Moreover, the frequencies of this variant did not differ statistically between T1DM patients and non-diabetic subjects when assuming recessive, dominant, or additive inheritance models. The clinical and laboratory characteristics of T1DM patients did not differ significantly among the three genotypes of the rs1893217 polymorphism, either. Conclusion: The PTPN2 rs1893217 polymorphism is not significantly associated with T1DM in Caucasian subjects from Southern Brazil.Objetivo: Avaliar a associação do polimorfismo rs1893217 no gene PTPN2 com DM1 e/ou suas características clínicas e laboratoriais em uma população de brancos do Sul do Brasil. Sujeitos e métodos: Quatrocentos e oitenta e seis pacientes com DM1 e 484 indivíduos não diabéticos foram incluídos no estudo. A genotipagem do PTPN2 rs1893217 foi realizada por PCR em tempo real. Resultados: As frequências genotípicas não diferiram entre os pacientes com DM1 e indivíduos não diabéticos (p = 0,265). O alelo C foi observado em 14,5% da amostra com DM1 e 12,2% no grupo de não diabéticos (p = 0,152). Além disso, as frequências dessa variante não diferiram estatisticamente entre os pacientes com DM1 e indivíduos não diabéticos considerando- se os modelos de herança recessivo, dominante ou aditivo. As características clínicas e laboratoriais dos pacientes com DM1 também não diferiram significativamente entre os três genótipos do polimorfismo rs1893217. Conclusão: O polimorfismo rs1893217 do gene PTPN2 não está associado com DM1 em brancos do Sul do Brasil

    Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas

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    Background: Esophageal squamous cell carcinoma (ESCC) shows a 5-year survival rate below 10%, demonstrating the urgency in improving its treatment. Alterations in epidermal growth factor receptors are closely related to malignancy transformation in a number of tumors and recent successful targeted therapies have been directed to these molecules. Therefore, in this study, we analyzed the expression of EGFR and HER2 and evaluated EGFR mutation profile as well as the presence of mutations in hotspots of KRAS and BRAF in ESCC patients. Methods: We performed RT-qPCR, immunohistochemistry and Fluorescent in situ hybridization to determine EGFR and HER2 expression in ESCC patients, and direct sequencing and PCR-RFLP for mutations and polymorphism analysis. Results: Our results showed an increased EGFR mRNA expression in tumors compared to surrounding tissue (p <0.05), with 11% of the cases presenting at least a four-fold difference between tumor and paired adjacent mucosa. EGFR protein overexpression was present only in 4% of the cases. The median expression of HER2 mRNA was not different between tumors and adjacent mucosa. Still, 7% of the tumors presented at least a 25-fold higher expression of this gene when compared to its paired counterpart. Immunohistochemical analysis revealed that 21% of the tumors were positive for HER2 (scores 2+ and 3+), although only 3+ tumors presented amplification of this gene. Mutation analysis for EGFR (exons 18-21), KRAS (codons 12 and 13) and BRAF (V600E) showed no mutations in any of the hotspots of these genes in almost 100 patients analyzed. EGFR presented synonymous polymorphisms at codon 836 (C>T) in 2.1% of the patients, and at codon 787 (G>A) in 79.2% of the cases. This last polymorphism was also evaluated in 304 healthy controls, which presented a similar frequency (73.7%) in comparison with ESCC patients. The absence of mutations of EGFR, KRAS and BRAF as well as the overexpression of EGFR and HER2 in less than 10% of the patients suggest that this signaling pathway is altered in only a small proportion of patients with ESCC. Conclusion: HER receptors target therapies may have the potential to be effective in only a minor fraction of patients with ESCC

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