489 research outputs found

    Corporal practices/physical activity and public policies of health promotion

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    A promoção da saúde, entendida como estratégia de produção social de saúde, deve articular e permear políticas públicas que influenciem o futuro da qualidade de vida urbana. Esse grande desafio envolve arranjos intersetoriais na gestão pública, empoderamento da população, desenvolvimento de competências e habilidades, capacitação, acesso à informação, estímulo à cidadania ativa, entre outros, para que a população reconheça seus problemas e suas causas, a fim de que ela possa advogar por políticas públicas saudáveis. Para esse propósito, é necessário que o governo operacionalize uma forma de gestão pública que considere a melhoria nas condições de vida, de trabalho e de cultura, estabelecendo uma relação harmoniosa com o meio ambiente, com o corpo que envolva a participação social na cogestão e na democracia. Nesse contexto, a inserção de um programa de práticas corporais/atividade física direcionada à população deve estar fundamentada em uma concepção da Promoção da Saúde apoiada em processos educativos que vão além da transmissão de conhecimentos. Ela deve estar focada no enfrentamento das dificuldades, no fortalecimento da identidade e na incorporação de soluções criativas e saberes saudáveis. Este artigo tem o objetivo de refletir sobre políticas de promoção da saúde relacionadas às Práticas Corporais/Atividade Física, além de apresentar um breve relato sobre o trabalho desenvolvido nessa área no município de São Paulo.Health promotion, understood as a strategy for the social production of health, must articulate and permeate public policies which influence the future of the urban quality of life. This great challenge involves intersectoral arrangements in public management, population empowerment, development of skills and competences, qualification, access to information, stimulus to an active citizenship, among other factors, so that the population recognizes its problems and their causes, and is able to claim for healthy public policies. To achieve this purpose, it is necessary that the government puts into operation a form of public management which takes into account the improvement in life, work, and cultural conditions, establishing a harmonious relationship with the environment and with the body. This relationship must involve social participation in joint management and in democracy. In this context, the insertion of a program of physical activities and corporal practices directed to the population must be based on a conception of Health Promotion supported by educational processes that go beyond knowledge transmission. It must be focused on facing difficulties, on the strengthening of the identity, and on the incorporation of creative solutions as well as healthy learning. The main objective of this paper is to reflect on health promotion policies related to corporal practices/physical activity and to provide a brief description of the activities developed in this area in the city of São Paulo

    Práticas corporais/atividade física e políticas públicas de promoção da saúde

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    Health promotion, understood as a strategy for the social production of health, must articulate and permeate public policies which influence the future of the urban quality of life. This great challenge involves intersectoral arrangements in public management, population empowerment, development of skills and competences, qualification, access to information, stimulus to an active citizenship, among other factors, so that the population recognizes its problems and their causes, and is able to claim for healthy public policies. To achieve this purpose, it is necessary that the government puts into operation a form of public management which takes into account the improvement in life, work, and cultural conditions, establishing a harmonious relationship with the environment and with the body. This relationship must involve social participation in joint management and in democracy. In this context, the insertion of a program of physical activities and corporal practices directed to the population must be based on a conception of Health Promotion supported by educational processes that go beyond knowledge transmission. It must be focused on facing difficulties, on the strengthening of the identity, and on the incorporation of creative solutions as well as healthy learning. The main objective of this paper is to reflect on health promotion policies related to corporal practices/physical activity and to provide a brief description of the activities developed in this area in the city of São Paulo.A promoção da saúde, entendida como estratégia de produção social de saúde, deve articular e permear políticas públicas que influenciem o futuro da qualidade de vida urbana. Esse grande desafio envolve arranjos intersetoriais na gestão pública, empoderamento da população, desenvolvimento de competências e habilidades, capacitação, acesso à informação, estímulo à cidadania ativa, entre outros, para que a população reconheça seus problemas e suas causas, a fim de que ela possa advogar por políticas públicas saudáveis. Para esse propósito, é necessário que o governo operacionalize uma forma de gestão pública que considere a melhoria nas condições de vida, de trabalho e de cultura, estabelecendo uma relação harmoniosa com o meio ambiente, com o corpo que envolva a participação social na cogestão e na democracia. Nesse contexto, a inserção de um programa de práticas corporais/atividade física direcionada à população deve estar fundamentada em uma concepção da Promoção da Saúde apoiada em processos educativos que vão além da transmissão de conhecimentos. Ela deve estar focada no enfrentamento das dificuldades, no fortalecimento da identidade e na incorporação de soluções criativas e saberes saudáveis. Este artigo tem o objetivo de refletir sobre políticas de promoção da saúde relacionadas às Práticas Corporais/Atividade Física, além de apresentar um breve relato sobre o trabalho desenvolvido nessa área no município de São Paulo

    Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort.

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    BackgroundUnderstanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.MethodsSeventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered-including molecular subgroup.ResultsThe majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy-assessed. Self-care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P = .02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P < .05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearing (P = .04). However, those who underwent a gross total resection reported having worse outcomes on the HUI3 vision (P = .02). No differences in HRQL were evident as a function of subgroup.ConclusionsBy examining an international sample of survivors, we characterized the worldwide impact of medulloblastoma. This is a critical first step in developing global standards for evaluating long-term outcomes

    Corpus Callosum Microstructural Changes Correlate with Cognitive Dysfunction in Early Stages of Relapsing-Remitting Multiple Sclerosis: Axial and Radial Diffusivities Approach

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    The corpus callosum is the largest fiber bundle in the central nervous system and it takes part in several cognitive pathways. It can be affected by multiple sclerosis (MS) early in the disease. DTI is capable of infering the microstructural organization of the white matter. The vectorial analysis of the DTI offers the more specific indices of axial diffusivity (AD) and radial diffusivity (RD), which have shown to be useful to discriminate myelin damage from axon loss, respectively. This study presents DTI results (mean diffusivity (MD), fractional anisotropy (FA), RD, and AD) of 23 relapsing-remitting MS patients and its correlation with cognitive performance. There were 47.8% of cognitive impaired patients (MS CI). We found signs of demyelination, reflected by increased RD, and incipient axon loss, reflected by AD increase, which was slightly higher in the MS CI. The cognitive changes correlated with the DTI parameters, suggesting that loss of complexity in CC connections can impair neural conduction. Thus, cognitive impairment can be related to callosal disconnection, and DTI can be a promising tool to evaluate those changes

    Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma

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    © Impact Journals, LLC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.This study was supported by the Canadian Cancer Society (Grant #2011-70051), the Pediatric Brain Tumor Foundation of the United States, the Brain Tumour Foundation of Canada, Meagan’s Walk, b.r.a.i.n.child and the Wiley Fund at the Hospital for Sick Children.info:eu-repo/semantics/publishedVersio

    Systems medicine of inflammaging

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    Systems Medicine (SM) can be defined as an extension of Systems Biology (SB) to Clinical-Epidemiological disciplines through a shifting paradigm, starting from a cellular, toward a patient centered framework. According to this vision, the three pillars of SM are Biomedical hypotheses, experimental data, mainly achieved by Omics technologies and tailored computational, statistical and modeling tools. The three SM pillars are highly interconnected, and their balancing is crucial. Despite the great technological progresses producing huge amount of data (Big Data) and impressive computational facilities, the Bio-Medical hypotheses are still of primary importance. A paradigmatic example of unifying Bio-Medical theory is the concept of Inflammaging. This complex phenotype is involved in a large number of pathologies and patho-physiological processes such as aging, age-related diseases and cancer, all sharing a common inflammatory pathogenesis. This Biomedical hypothesis can be mapped into an ecological perspective capable to describe by quantitative and predictive models some experimentally observed features, such as microenvironment, niche partitioning and phenotype propagation. In this article we show how this idea can be supported by computational methods useful to successfully integrate, analyze and model large data sets, combining cross-sectional and longitudinal information on clinical, environmental and omics data of healthy subjects and patients to provide new multidimensional biomarkers capable of distinguishing between different pathological conditions, e.g. healthy versus unhealthy state, physiological versus pathological aging

    Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin

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    Sphingosine-1-phosphate (S1P) participates in inflammation;however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P(3)) and G alpha(q), PLC beta and Ca2+. Intraarterial S1P administration increases leukocyte rolling, while S1P(3) deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P(3). Histamine and epinephrine require S1P(3) for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P1 inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific S1P(1)(-/-) mice. In agreement with a dominant pro-rolling effect of S1P(3),FTY720 inhibits rolling in control and S1P(1)(-/-) but not in S1P(3)(-/-) mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action

    Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors

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    Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor in infants that is characterized by loss of nuclear expression of SMARCB1 or SMARCA4 proteins. Recent studies show that AT/RTs comprise three molecular subgroups, namely AT/RT-TYR, AT/RT-MYC and AT/RT-SHH. The subgroups show distinct expression patterns of genes involved in ciliogenesis, however, little is known about the functional roles of primary cilia in the biology of AT/RT. Here, we show that primary cilia are present across all AT/RT subgroups with specific enrichment in AT/RT-TYR patient samples. Furthermore, we demonstrate that primary ciliogenesis contributes to AT/RT biology in vitro and in vivo. Specifically, we observed a significant decrease in proliferation and clonogenicity following disruption of primary ciliogenesis in AT/RT cell line models. Additionally, apoptosis was significantly increased via the induction of STAT1 and DR5 signaling, as detected by proteogenomic profiling. In a Drosophila model of SMARCB1 deficiency, concomitant knockdown of several cilia-associated genes resulted in a substantial shift of the lethal phenotype with more than 20% of flies reaching adulthood. We also found significantly extended survival in an orthotopic xenograft mouse model of AT/RT upon disruption of primary ciliogenesis. Taken together, our findings indicate that primary ciliogenesis or its downstream signaling contributes to the aggressiveness of AT/RT and, therefore, may constitute a novel therapeutic target

    Single-cell transcriptomics identifies potential cells of origin of MYC rhabdoid tumors

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    Rhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we establish and characterize different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets. From all models only Sox2-positive progenitor cells give rise to murine RT. Using single-cell analyses, we identify distinct cells of origin for the SHH and MYC subgroups of RT, rooting in early stages of embryogenesis. Intra- and extracranial MYC tumors harbor common genetic programs and potentially originate from fetal primordial germ cells (PGCs). Using PGC specific Smarcb1 knockout mouse models we validate that MYC RT originate from these progenitor cells. We uncover an epigenetic imbalance in MYC tumors compared to PGCs being sustained by epigenetically-driven subpopulations. Importantly, treatments with the DNA demethylating agent decitabine successfully impair tumor growth in vitro and in vivo. In summary, our work sheds light on the origin of RT and supports the clinical relevance of DNA methyltransferase inhibitors against this disease
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