Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: Results from a pooled analysis

Background: Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting. Methods: We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients). Results: Overall response rate was 43.5 % in patients treated with monotherapy and 51.3 % with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2 % versus 21.7 %; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9 % versus 43.5 %; p = 0.05). Conclusions: In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting

Unfolding of the Amyloid β-Peptide Central Helix: Mechanistic Insights from Molecular Dynamics Simulations

Alzheimer's disease (AD) pathogenesis is associated with formation of amyloid fibrils caused by polymerization of the amyloid β-peptide (Aβ), which is a process that requires unfolding of the native helical structure of Aβ. According to recent experimental studies, stabilization of the Aβ central helix is effective in preventing Aβ polymerization into toxic assemblies. To uncover the fundamental mechanism of unfolding of the Aβ central helix, we performed molecular dynamics simulations for wild-type (WT), V18A/F19A/F20A mutant (MA), and V18L/F19L/F20L mutant (ML) models of the Aβ central helix. It was quantitatively demonstrated that the stability of the α-helical conformation of both MA and ML is higher than that of WT, indicating that the α-helical propensity of the three nonpolar residues (18, 19, and 20) is the main factor for the stability of the whole Aβ central helix and that their hydrophobicity plays a secondary role. WT was found to completely unfold by a three-step mechanism: 1) loss of α-helical backbone hydrogen bonds, 2) strong interactions between nonpolar sidechains, and 3) strong interactions between polar sidechains. WT did not completely unfold in cases when any of the three steps was omitted. MA and ML did not completely unfold mainly due to the lack of the first step. This suggests that disturbances in any of the three steps would be effective in inhibiting the unfolding of the Aβ central helix. Our findings would pave the way for design of new drugs to prevent or retard AD

Prevalence and Factors Associated with Leishmania infantum Infection of Dogs from an Urban Area of Brazil as Identified by Molecular Methods

Visceral leishmaniasis (VL) is a disease caused by the parasite Leishmania infantum, and dogs are the most important domestic reservoirs of the agent. During recent decades, VL has expanded to large Brazilian urban centers. In the present work, we have demonstrated by using molecular techniques that the rate of canine infection as detected by serology has been considerably underestimated. Two groups of seronegative dogs (infected and non-infected according to molecular methods) were further evaluated from data obtained through interviews with owners of the animals. The factors associated with Leishmania infection in dogs were a family income of less than two minimum salaries, the knowledge of the owner regarding the vector, the dog spending most of its time in the backyard and the dog never having had a previous serological examination. Awareness regarding the factors associated with canine infection will improve health services and the understanding of the disease's expansion in urban areas

Quality of life, knowledge and attitude after educational program for Diabetes Qualidade de vida, conhecimento e atitude após programa educativo para Diabetes Corresponding author

Abstract Objective: To assess the quality of life, knowledge about the disease and the attitude of individuals with type 2 diabetes mellitus before and after participation in an educational program. Methods: Quasi-experimental study conducted with 110 patients seen at the clinic of a teaching hospital. In the Control Group subjects received routine care (n=74) and in the Experimental Group received routine care and participated in educational interventions (n=36). The WHOQOL-BREF and B-PAID were used to assess the quality of life; DKN-A to assess the knowledge and the ATT-19 to assess attitude. Results: There was improvement in quality of life after participation in the educational program, particularly in social relations domain; decrease the suffering of living with DM and knowledge acquisition were statistically significant. Attitude increase was discreet. Conclusion: The educational program for DM2 contributed to increase quality of life, with reduction of suffering; increased knowledge about disease, treatment and better coping the disease. Resumo Objetivo: Avaliar a qualidade de vida, o conhecimento sobre a doença e a atitude de indivíduos com diabetes mellitus tipo 2 antes e após participação em programa educativo. Métodos: Estudo quase experimental, realizado com 110 indivíduos atendidos no ambulatório de um Hospital Universitário. No Grupo Controle, os indivíduos receberam o atendimento de rotina (n=74) e no Grupo Teste, além de receber o acompanhamento de rotina participaram das intervenções educativas (n=36). Foram utilizados o Whoqol-bref e o B-PAID para avaliar a qualidade de vida; DKN-A para avaliação do conhecimento e o ATT-19, a atitude. Resultados: Houve melhora da qualidade de vida após participação no programa educativo, particularmente, no domínio Relações sociais; diminuição do sofrimento em viver com DM e aquisição de conhecimento estatisticamente significante. Na atitude o aumento foi discreto. Conclusão: O programa educativo para DM2 contribuiu para o aumento da qualidade de vida, com diminuição do sofrimento; aumento do conhecimento sobre a doença, tratamento e melhor enfrentamento a doença

Recruitment of Discrete Regions of the Psoas Major and Quadratus Lumborum Muscles Is Changed in Specific Sitting Postures in Individuals With Recurrent Low Back Pain

STUDY DESIGN: Cross-sectional controlled laboratory study.