Using the Ophelia (Optimising Health Literacy and Access to Health Services) process as a practical tool for health promotion program delivery in various Philippine communities.

ISSUE ADDRESSED: The Ophelia (Optimising Health Literacy and Access to Health Services) process can be used as a practical tool for effective health promotion program delivery because of its multi-sector and pragmatic approach to designing health interventions. An initial case study showed how its first phase was successfully adapted in a pilot community in Leyte, Philippines. In this study, the three phases of the Ophelia process were implemented in Leyte, along with additional communities in Mindoro and Surigao. METHODS: After conducting needs assessment and community profiling in phase 1, the results were transformed into vignettes, hypothetical personas representing the health needs of the community. These were used in phase 2, which involved focus group discussions and workshops to cocreate intervention ideas with government organisations, practitioners, and community representatives. A rapid realist review was conducted in phase 3 to check for the feasibility of interventions. RESULTS: Through this, the top evidence-based health interventions for each life stage were listed and presented for prioritisation. Program implementation and impact evaluation plans were created for the top health intervention prior to implementation. CONCLUSIONS: The Ophelia process ensured that health promotion interventions addressed community needs and were designed using community resources and the wisdom of health practitioners that have been immersed in the local health system. SO WHAT?: The study demonstrated the usefulness of vignettes in presenting data to lay people and how the rapid realist review approach is a practical tool for policy-makers to ensure that program plans designed by the communities and health practitioners are evidence-based without sacrificing the timeliness of implementation.

Deptor enhances triple-negative breast cancer metastasis and chemoresistance through coupling to survivin expression.

Transforming growth factor-ß (TGF-ß) functions to suppress tumorigenesis in normal mammary tissues and early-stage breast cancers and, paradoxically, acts to promote the metastasis and chemoresistance in late-stage breast cancers, particularly triple-negative breast cancers (TNBCs). Precisely how TGF-ß acquires oncogenic characteristics in late-stage breast cancers remains unknown, as does the role of the endogenous mammalian target of rapamycin (mTOR) inhibitor, Dep domain-containing mTOR-interacting protein (Deptor), in coupling TGF-ß to TNBC development and metastatic progression. Here we demonstrate that Deptor expression was downregulated in basal-like/TNBCs relative to their luminal counterparts. Additionally, Deptor expression was 1) inversely correlated with the metastatic ability of human (MCF10A) and mouse (4T1) TNBC progression series and 2) robustly repressed by several inducers of epithelial-mesenchymal transition programs. Functional disruption of Deptor expression in 4T07 cells significantly inhibited their proliferation and organoid growth in vitro, as well as prevented their colonization and tumor formation in the lungs of mice. In stark contrast, elevated Deptor expression was significantly associated with poorer overall survival of patients harboring estrogen receptor α-negative breast cancers. Accordingly, enforced Deptor expression in MDA-MB-231 cells dramatically enhanced their 1) organoid growth in vitro, 2) pulmonary outgrowth in mice, and 3) resistance to chemotherapies, an event dependent on the coupling of Deptor to survivin expression. Collectively, our findings highlight the dichotomous functions of Deptor in modulating the proliferation and survival of TNBCs during metastasis; they also implicate Deptor and its stimulation of survivin as essential components of TNBC resistance to chemotherapies and apoptotic stimuli.