Effects of health at every size® interventions on health-related outcomes of people with overweight and obesity: a systematic review.

CONTEXT: The growing use of interventions based on the Health at Every Size® (HAES®) in obesity management. OBJECTIVE: This study aimed to summarize the health-related effects of HAES®-based interventions on people with overweight and obesity. DATA SOURCES: MEDLINE (via PubMed), EMBASE, Cochrane Library, LILACS, Google Scholar, OpenGrey and Grey Literature Report. STUDY SELECTION: A systematic review of studies published until January 2017 reporting on HAES®-based randomized and non-randomized controlled trials in people with overweight and/or obesity. DATA EXTRACTION: Fourteen papers met the inclusion criteria. The assessed studies included the following tests: blood profile, blood pressure, anthropometry, eating behaviour, energy intake, diet quality, psychological and qualitative evaluations. RESULTS: The HAES® interventions benefited both the psychological and physical activity outcomes, besides promoting behavioural and qualitative changes in eating habits. On the other hand, the results regarding cardiovascular responses, body-image perception and total energy intake were inconsistent. CONCLUSIONS: Despite improving the cardiovascular status, eating behaviours, quality of life and psychological well-being in participants, other large long-term clinical trials should be performed to establish the effectiveness of HAES®-based interventions in improving health for people with overweight and obesity. PROSPERO registration 2017: CRD42017054857.

Three-dimensional microenvironment confers enhanced sensitivity to doxorubicin by reducing p53-dependent induction of autophagy.

Preclinical studies of anticancer drugs are typically performed using cancer cell lines maintained in two-dimensional (2D) cultures, ignoring the influences of the extracellular matrix (ECM) and three-dimensional (3D) microenvironment. In this study, we evaluated the microenvironmental control of human breast cancer cells responses to doxorubicin (DOXO) using the 3D laminin-rich ECM (3D lrECM) cell culture model. Under 3D culture conditions, MCF-7 cells displayed drastic morphological alterations, a decrease in proliferation and elevated sensitivity to DOXO. Interestingly, the chemotherapy-mediated activation of autophagy was compromised in the 3D matrix, suggesting an association between the increased cytotoxicity of DOXO and hindered autophagy induction. Indeed, while chloroquine or ATG5 knockdown potentiated DOXO-induced cell death under the 2D culture conditions, the autophagy inducer rapamycin improved the resistance of 3D-cultured cells to this drug. Moreover, in the monolayer-cultured cells, DOXO treatment led to increases in p53 and DRAM-1 expression, which is a p53-dependent activator of autophagy that functions in response to DNA damage. Conversely, p53 and DRAM-1 expression was impaired in 3D-cultured cells. The knockdown of p53 by shRNA blocked DRAM-1 activation, impaired autophagy induction and sensitized only those cells maintained under 2D conditions to DOXO. In addition, 2D-cultured MDA-MB-231 cells (a p53-mutated breast cancer cell line) not only showed increased sensitivity to DOXO compared with MCF-7 cells but also failed to induce DRAM-1 expression or autophagy. Similar to p53 silencing, DRAM-1 knockdown potentiated DOXO cytotoxicity only in 2D-cultured cells. These results suggest that the 3D tissue microenvironment controls tumor cell sensitivity to DOXO treatment by preventing p53-DRAM-autophagy axis activation.

Autophagy and genomic integrity.

DNA lesions, constantly produced by endogenous and exogenous sources, activate the DNA damage response (DDR), which involves detection, signaling and repair of the damage. Autophagy, a lysosome-dependent degradation pathway that is activated by stressful situations such as starvation and oxidative stress, regulates cell fate after DNA damage and also has a pivotal role in the maintenance of nuclear and mitochondrial genomic integrity. Here, we review important evidence regarding the role played by autophagy in preventing genomic instability and tumorigenesis, as well as in micronuclei degradation. Several pathways governing autophagy activation after DNA injury and the influence of autophagy upon the processing of genomic lesions are also discussed herein. In this line, the mechanisms by which several proteins participate in both DDR and autophagy, and the importance of this crosstalk in cancer and neurodegeneration will be presented in an integrated fashion. At last, we present a hypothetical model of the role played by autophagy in dictating cell fate after genotoxic stress.

Estudo dos defeitos da impregnacao neuroleptica em pacientes esquizofrenicos atraves do metodo de Rorschach. / Effects of neuroleptic impregnation in schizophrenic patients by Rorschach method

Os autores pretendem estudar os efeitos do fenomeno de impregnacao neuroleptica - sindrome extrapiramidal - no processo terapeutico de pacientes exquizofrenicos. E bem conhecido que a impregnacao neuroleptica e o resultado da acao do neuroleptico nos nucleos basais do cerebro. Seus efeitos clinicos levam a uma acao antipsicotica seguida da remissao das alucinacoes e delirios nestes pacientes. Deste modo, pacientes com o diagnostico psiquiatrico de esquizofrenia paranoide (segundo Kraepelin e Bleuler) foram selecionados e submetidos ao exame de Rorschach em dois momentos: antes e durante a impregnacao.Estes pacientes foram selecionados entre aqueles internados no Hospital Psiquiatrico de Vila Mariana. Pacientes entre 25 e 35 anos foram examinadas psiquiatrica e psicologicamente