ABSTRACT
Cardiotoxicity is a major side effect of the chemotherapeutic drug doxorubicin (Dox), which is further exacerbated when it is combined with trastuzumab, a standard care approach for Human Epidermal growth factor Receptor-type 2 (HER2) positive cancer patients. However, the molecular mechanisms of the underlying cardiotoxicity of this combination are still mostly elusive. Increased oxidative stress, impaired energetic substrate uses and topoisomerase IIB inhibition are among the biological processes proposed to explain Dox-induced cardiomyocyte dysfunction. Since cardiomyocytes express HER2, trastuzumab can also damage these cells by interfering with neuroregulin-1 signaling and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt and focal adhesion kinase (FAK)-dependent pathways. Nevertheless, Dox and trastuzumab target other cardiac cell types, such as endothelial cells, fibroblasts, cardiac progenitor cells and leukocytes, which can contribute to the clinical cardiotoxicity observed. This review aims to summarize the current knowledge on the cardiac signaling pathways modulated by these two antineoplastic drugs highly used in the management of breast cancer, not only focusing on cardiomyocytes but also to broaden the knowledge of the potential impact on other cells found in the heart.
Subject(s)
Antineoplastic Agents/adverse effects , Cardiotoxicity/etiology , Doxorubicin/adverse effects , Trastuzumab/adverse effects , Animals , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cardiotoxicity/metabolism , Cardiotoxicity/pathology , Humans , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Neuregulin-1/metabolism , Oxidative Stress/drug effects , Receptor, ErbB-2/metabolism , Signal Transduction/drug effectsABSTRACT
With the increasing presence of renewable energy sources in the electrical power grid, demand response via thermostatic appliances such as electric water heaters is a promising way to compensate for the significant variability in renewable power generation. We propose a multistage stochastic optimization model that computes the optimal day-ahead target profile of the mean thermal energy contained in a large population of heaters, given various possible wind power production and uncontrollable load scenarios. This optimal profile is calculated to make the variable net demand as even as possible.
Subject(s)
Antineoplastic Agents , Neoplasms , Drug Development , Nanotechnology , Neoplasms/drug therapyABSTRACT
INTRODUCTION: Nutrition has been underrepresented in the curriculum of many medical schools and therefore physicians do not feel adequately prepared to provide dietary counselling. The aim of the present study is to determine the impact of a Nutrition and Metabolism curricular unit on nutrition attitudes, knowledge and confidence on future clinical practice of medical students. MATERIAL AND METHODS: All the students enrolled in the curricular unit (2017/2018) were invited to complete a questionnaire assessing their nutritional knowledge and eating habits at the beginning and at the end of the semester (n = 310). RESULTS: Initially, students reported good eating habits and nutrition knowledge. These aspects improved at the end of the study. Moreover, students reported that they felt more confident to do dietary counselling after intervention. DISCUSSION: Most medical students answered affirmatively to all questions related with good habits or eating behaviours, and the acquisition of knowledge had an impact in specific attitudes. After the Nutrition and Metabolism classes the students felt able to provide dietary counselling in different clinical settings, but none of the students felt extremely confident about their competencies for dietary counselling. This can be due to the fact that the students involved were in the first year of the integrated master's degree in medicine, which is a preclinical year, and thus distant from the medical reality and from contact with patients. CONCLUSION: Nutrition education can have a positive impact on attitudes and eating behaviours, knowledge and in the perception of competencies for dietary counselling.
Introdução: A nutrição não tem sido uma prioridade no programa curricular de muitas escolas médicas e, portanto, os médicos não se sentem devidamente preparados para realizar aconselhamento alimentar. O objetivo deste estudo consiste em determinar o impacto do ensino de Nutrição e Metabolismo nas atitudes e comportamentos, conhecimento e confiança na prática clínica futura dos alunos de medicina. Material e Métodos: Todos os estudantes (n = 310) inscritos na unidade curricular (2017/2018) foram convidados a preencher um questionário, no início e no final do semestre, para avaliar os seus hábitos e conhecimentos alimentares. Resultados: Inicialmente, os estudantes apresentavam bons hábitos alimentares e um bom conhecimento nutricional. Não obstante, no final do estudo verificou-se que estes parâmetros melhoraram. Mais ainda, após a unidade curricular os estudantes sentiam-se mais confiantes para realizar aconselhamento nutricional. Discussão: Após a unidade curricular, a maioria dos estudantes respondeu afirmativamente às questões referentes a atitudes e comportamentos alimentares, sendo que a aquisição de novos conhecimentos pode ser responsável pelo aumento significativo de respostas afirmativas a determinadas questões. Os estudantes sentiram-se capazes de realizar aconselhamento alimentar em diferentes contextos clínicos, mas foram poucos os que reportaram sentir-se fortemente confiantes. Tal pode dever-se ao facto de frequentarem o primeiro ano do mestrado integrado em medicina, ano pré-clínico, sem contacto com a prática médica e com o doente. Conclusão: Pode verificar-se que o ensino de Nutrição numa escola médica teve impacto positivo nas atitudes e comportamentos alimentares, conhecimento e perceção de competências para a realização de aconselhamento nutricional.
