Interventions to Modify Psychological Well-Being: Progress, Promises, and an Agenda for Future Research

Psychological well-being, characterized by feelings, cognitions, and strategies that are associated with positive functioning (including hedonic and eudaimonic well-being), has been linked with better physical health and greater longevity. Importantly, psychological well-being can be strengthened with interventions, providing a strategy for improving population health. But are the effects of well-being interventions meaningful, durable, and scalable enough to improve health at a population-level? To assess this possibility, a cross-disciplinary group of scholars convened to review current knowledge and develop a research agenda. Here we summarize and build on the key insights from this convening, which were: (1) existing interventions should continue to be adapted to achieve a large-enough effect to result in downstream improvements in psychological functioning and health, (2) research should determine the durability of interventions needed to drive population-level and lasting changes, (3) a shift from individual-level care and treatment to a public-health model of population-level prevention is needed and will require new infrastructure that can deliver interventions at scale, (4) interventions should be accessible and effective in racially, ethnically, and geographically diverse samples. A discussion examining the key future research questions follows

Interventions to modify psychological well-being:Progress, promises, and an agenda for future research

Psychological well-being, characterized by feelings, cognitions, and strategies that are associated with positive functioning (including hedonic and eudaimonic well-being), has been linked with better physical health and greater longevity. Importantly, psychological well-being can be strengthened with interventions, providing a strategy for improving population health. But are the effects of well-being interventions meaningful, durable, and scalable enough to improve health at a population-level? To assess this possibility, a cross-disciplinary group of scholars convened to review current knowledge and develop a research agenda. Here we summarize and build on the key insights from this convening, which were: (1) existing interventions should continue to be adapted to achieve a large-enough effect to result in downstream improvements in psychological functioning and health, (2) research should determine the durability of interventions needed to drive population-level and lasting changes, (3) a shift from individual-level care and treatment to a public-health model of population-level prevention is needed and will require new infrastructure that can deliver interventions at scale, (4) interventions should be accessible and effective in racially, ethnically, and geographically diverse samples. A discussion examining the key future research questions follows

FGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal cancer

Fibroblast growth factor receptor 4 (FGFR4) is vital in early development and tissue repair. FGFR4 expression levels are very restricted in adult tissues, except in several solid tumors including colorectal cancer, which showed overexpression of FGFR4. Here, FGFR4 mutation analysis discarded the presence of activating mutations, other than Arg388, in different colorectal cancer cell lines and tumoral samples. Stable shRNA FGFR4-silencing in SW480 and SW48 cell lines resulted in a significant decrease in cell proliferation, adhesion, cell migration and invasion. This decrease in the tumorigenic and invasive capabilities of colorectal cancer cells was accompanied by a decrease of Snail, Twist and TGFβ gene expression levels and an increase of E-cadherin, causing a reversion to a more epithelial phenotype, in three different cell lines. In addition, FGFR4-signaling activated the oncogenic SRC, ERK1/2 and AKT pathways in colon cancer cells and promoted an increase in cell survival. The relevance of FGFR4 in tumor growth was supported by two different strategies. Kinase inhibitors abrogated FGFR4-related cell growth and signaling pathways at the same extent than FGFR4-silenced cells. Specific FGFR4-targeting using antibodies provoked a similar reduction in cell growth. Moreover, FGFR4 knock-down cells displayed a reduced capacity for in vivo tumor formation and angiogenesis in nude mice. Collectively, our data support a crucial role for FGFR4 in tumorigenesis, invasion and survival in colorectal cancer. In addition, FGFR4 targeting demonstrated its applicability for colorectal cancer therapy.This research was supported by grant BIO2009-08818 from the Spanish Ministry of Science and Innovation, grant to established research groups (AECC) and grant S2011/BMD-2344/Colomics2 from Comunidad de Madrid