Developing the Active Communities Tool to Implement the Community Guide\u27s Built Environment Recommendation for Increasing Physical Activity

Physical activity is higher in communities that include supportive features for walking and bicycling. In 2016, the Community Preventive Services Task Force released a systematic review of built environment approaches to increase physical activity. The results of the review recommended approaches that combine interventions to improve pedestrian and bicycle transportation systems with land use and environmental design strategies. Because the recommendation was multifaceted, the Centers for Disease Control and Prevention determined that communities could benefit from an assessment tool to address the breadth of the Task Force recommendations. The purpose of this article is to describe the systematic approach used to develop the Active Communities Tool. First, we created and refined a logic model and community theory of change for tool development. Second, we reviewed existing community-based tools and abstracted key elements (item domains, advantages, disadvantages, updates, costs, permissions to use, and psychometrics) from 42 tools. The review indicated that no tool encompassed the breadth of the Community Guide recommendations for communities. Third, we developed a new tool and pilot tested its use with 9 diverse teams with public health and planning expertise. Final revisions followed from pilot team and expert input. The Active Communities Tool comprises 6 modules addressing all 8 interventions recommended by the Task Force. The tool is designed to help cross-sector teams create an action plan for improving community built environments that promote physical activity and may help to monitor progress toward achieving community conditions known to promote physical activity

Association of the Epithelial-to-Mesenchymal Transition (EMT) Phenotype with Responsiveness to the p21-Activated Kinase Inhibitor, PF-3758309, in Colon Cancer Models

The p21-activated kinase (PAK) family of serine/threonine kinases, which are overexpressed in several cancer types, are critical mediators of cell survival, motility, mitosis, transcription, and translation. In the study presented here we utilized a panel of CRC cell lines to identify potential biomarkers of sensitivity or resistance that may be used to individualize therapy to the PAK inhibitor PF-03758309. We observed a wide range of proliferative responses in the CRC cell lines exposed to PF-03758309, this response was recapitulated in other phenotypic assays such as anchorage-independent growth, three dimensional tumor spheroid formation, and migration. Interestingly, we observed that cells most sensitive to PF-03758309 exhibited up regulation of genes associated with a mesenchymal phenotype (CALD1, VIM, ZEB1) and cells more resistant had an up regulation of genes associated with an epithelial phenotype (CLDN2, CDH1, CLDN3, CDH17) allowing us to derive an epithelial-to-mesenchymal transition (EMT) gene signature for this agent. We assessed the functional role of EMT-associated genes in mediating responsiveness to PF-3758309, by targeting known genes and transcriptional regulators of EMT. We observed that suppression of genes associated with the mesenchymal phenotype conferred resistance to PF-3758309, in vitro and in vivo. These results indicate that PAK inhibition is associated with a unique response phenotype in CRC and that further studies should be conducted to facilitate both patient selection and rational combination strategies with these agents