RESUMO
Frailty requires concerted integrated approaches to prevent functional decline. Although there is evidence that integrating care is effective for older people, there is insufficient data on outcomes from studies implementing integrated care to prevent and manage frailty. We systematically searched PubMed and Cochrane Library database for peer-reviewed medical literature on models of care for frailty, published from 2002 to 2017. We considered the effective and transferable components of the models of care and evidence of economic impact, where available. Information on European Union-funded projects or those registered with the European Innovation Partnership on Active and Healthy Ageing, and grey literature (including good practices) were also considered. We found 1,065 potential citations and 170 relevant abstracts. After excluding reports on specific diseases, processes or interventions and service models that did not report data, 42 full papers met the inclusion criteria. The evidence showed that few models of integrated care were specifically designed to prevent and tackle frailty in the community and at the interface between primary and secondary (hospital) care. Current evidence supports the case for a more holistic and salutogenic response to frailty, blending a chronic care approach with education, enablement and rehabilitation to optimise function, particularly at times of a sudden deterioration in health, or when transitioning between home, hospital or care home. In all care settings, these approaches should be supported by comprehensive assessment and multidimensional interventions tailored to modifiable physical, psychological, cognitive and social factors.
RESUMO
The Trk family of neurotrophin tyrosine kinase receptors is emerging as an important player in carcinogenic progression in non-neuronal tissues. Here, we show that breast tumors present high levels of TrkA and phospho-TrkA compared to normal breast tissues. To further evaluate the precise functions of TrkA overexpression in breast cancer development, we have performed a series of biological tests using breast cancer cells that stably overexpress TrkA. We show that (1) TrkA overexpression promoted cell growth, migration and invasion in vitro; (2) overexpression of TrkA per se conferred constitutive activation of its tyrosine kinase activity; (3) signal pathways including PI3K-Akt and ERK/p38 MAP kinases were activated by TrkA overexpression and were required for the maintenance of a more aggressive cellular phenotype; and (4) TrkA overexpression enhanced tumor growth, angiogenesis and metastasis of xenografted breast cancer cells in immunodeficient mice. Moreover, recovered metastatic cells from the lungs exhibited enhanced anoikis resistance that was abolished by the pharmacological inhibitor K252a, suggesting that TrkA-promoted breast tumor metastasis could be mediated at least in part by enhancing anoikis resistance. Together, these results provide the first direct evidence that TrkA overexpression enhances the tumorigenic properties of breast cancer cells and point to TrkA as a potential target in breast cancer therapy.
Assuntos
Neoplasias da Mama/genética , Proliferação de Células , Receptor trkA/genética , Animais , Anoikis/fisiologia , Biópsia , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Linhagem Celular Tumoral , Movimento Celular , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Feminino , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos SCID , Invasividade Neoplásica , Metástase Neoplásica , Neovascularização Patológica , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologiaRESUMO
Over a period of 19 months, 33 cases of acute allergic contact dermatitis from Veet epilating waxes and/or the accompanying tissue (Reckitt Benckiser, Massy, France) were observed in France and Belgium. The lesions started on the legs and spread to other parts of the body, especially the face, and were sometimes so severe that hospitalization and/or systemic corticosteroids were required. Primary sensitization occurred as early as after the first application in several patients. Patch tests were performed in 26 of the patients and produced strong positive reactions to the tissue (25 times) and/or the wax (13 times). The allergenic culprits in the wax were modified-colophonium derivatives (colophonium in the standard series testing negatively in all except 4 patients), while methoxy PEG-22/dodecyl glycol copolymer and to a lesser degree lauryl alcohol turned out to be the main causal allergens in the tissue.