RESUMO
Stepped-care (SC) models have been adopted in primary care settings as a method for treating mental health conditions within primary care. In a SC model, a patient's symptoms are assessed, and an intervention is prescribed that matches the severity of symptoms. Thus, the SC model offers a variety of steps and levels of treatment that range from low to high intensity. Progression in treatment is monitored on a weekly basis and patients are stepped up or down in level of care depending on their clinical response to the intervention.
Assuntos
Depressão , Aplicativos Móveis , Humanos , Depressão/terapia , Atenção Primária à Saúde/métodos , Saúde MentalRESUMO
Senescence, the state of permanent cell cycle arrest, has been associated with endothelial cell dysfunction and atherosclerosis. The cyclin dependent kinase inhibitors p21(CIP1/WAF1) and p16(INK4a) govern the G(1)/S cell cycle checkpoint and are essential for determining whether a cell enters into an arrested state. The homeodomain transcription factor MEOX2 is an important regulator of vascular cell proliferation and is a direct transcriptional activator of both p21(CIP1/WAF1) and p16(INK4a). MEOX1 and MEOX2 have been shown to be partially functionally redundant during development, suggesting that they regulate similar target genes in vivo. We compared the ability of MEOX1 and MEOX2 to activate p21(CIP1/WAF1) and p16(INK4a) expression and induce endothelial cell cycle arrest. Our results demonstrate for the first time that MEOX1 regulates the MEOX2 target genes p21(CIP1/WAF1) and p16(INK4a). In addition, increased expression of either of the MEOX homeodomain transcription factors leads to cell cycle arrest and endothelial cell senescence. Furthermore, we show that the mechanism of transcriptional activation of these cyclin dependent kinase inhibitor genes by MEOX1 and MEOX2 is distinct. MEOX1 and MEOX2 activate p16(INK4a) in a DNA binding dependent manner, whereas they induce p21(CIP1/WAF1) in a DNA binding independent manner.
