The cellular movements that construct a macropinosome have a corresponding sequence of chemical transitions in the cup-shaped region of plasma membrane that becomes the macropinosome. To determine the relative positions of type I phosphatidylinositol 3-kinase (PI3K) and phospholipase C (PLC) in this pathway, we analyzed macropinocytosis in macrophages stimulated by the growth factor macrophage-colony-stimulating factor (M-CSF) and by the diacylglycerol (DAG) analog phorbol 12-myristate 13-acetate (PMA). In cells stimulated with M-CSF, microscopic imaging of fluorescent probes for intracellular lipids indicated that the PI3K product phosphatidylinositol (3,4,5)-trisphosphate (PIP3) appeared in cups just prior to DAG. We then tested the hypothesis that PMA and DAG function after PI3K and prior to Ras and protein kinase C (PKC) during macropinosome formation in macrophages. Although the PI3K target Akt was activated by M-CSF, the Akt inhibitor MK-2206 did not inhibit macropinocytosis. The phospholipase C (PLC) inhibitor U73122 blocked macropinocytosis by M-CSF but not PMA. Macropinocytosis in response to M-CSF and PMA was inhibited by the Ras inhibitor farnesyl thiosalicylate (FTS), by the PKC inhibitor Calphostin C and by the broad specificity inhibitor rottlerin. These studies support a model in which M-CSF stimulates PI3K in macropinocytic cups, and the resulting increase in PIP3 activates PLC, which in turn generates DAG necessary for activation of PKC, Ras and the late stages of macropinosome closure.

Background: A history of unethical research and deficit-based paradigms have contributed to profound mistrust of research among Native Americans, serving as an important call to action. Lack of cultural safety in research with Native Americans limits integration of cultural and contextual knowledge that is valuable for understanding challenges and making progress toward sustainable change. Aim: To identify strategies for promoting cultural safety, accountability, and sustainability in research with Native American communities. Method: Using an integrative review approach, three distinct processes were carried out: (1) appraisal of peer-reviewed literature (Scopus, PubMed, and ProQuest), (2) review of grey literature (e.g. policy documents and guidelines), and (3) synthesis of recommendations for promoting cultural safety. Results: A total of 378 articles were screened for inclusion, with 55 peer-reviewed and grey literature articles extracted for full review. Recommendations from included articles were synthesised into strategies aligned with eight thematic areas for improving cultural safety in research with Native American communities. Conclusions: Research aiming to understand, respect, and acknowledge tribal sovereignty, address historical trauma, and endorse Indigenous methods is essential. Culturally appropriate, community-based and -engaged research collaborations with Native American communities can signal a reparative effort, re-establish trust, and inform pragmatic solutions. Rigorous research led by Native American people is critical to address common and complex health challenges faced by Native American communities. Impact statement: Respect and rigorous methods ensure cultural safety, accountability, and sustainability in research with Native Americans.

Objective The purpose of this study is to describe the experiences of home-based care providers (HBCP)  in providing care to older adults during the pandemic in order to inform future disaster planning, including during pandemics. Design Qualitative inquiry using an abductive analytic approach. Setting and participants Home-based care providers in COVID-19 hotspots. Methods Telephone interviews were conducted with 27 participants (administrators, registered nurses and other members of the allied healthcare team), who provided in-home care during the pandemic in Medicare-certified home health agencies. Interviews focused on eliciting experiences from HBCP on challenges and successes in providing home-based care to older adults, including barriers to care and strategies employed to keep patients, and providers, safe in their homes during the pandemic. Results Data was distilled into four major themes that have potential policy and practice impact. These included disrupted aging-in-place resources, preparedness actions contributing to readiness for the pandemic, limited adaptability in administrative needs during the pandemic and challenges with unclear messaging from public health officials. Conclusions Home-based care plays an essential role in maintaining the health of older adults in disaster contexts, including pandemics. Innovative solutions, informed by policy that generate evidence-based best practices to support HBCP are needed to reduce barriers and increase protective factors, in order to maintain continuity of care for this vulnerable population during disruptive events.

Background During a disaster, home-based care fills the critical need for continuation of health care. Home-based care is intended to function using existing care delivery models, continuing to provide care for patients wherever they are located, including in shelters and hotels. Home-based care providers are often the closest in contact with their patients —seeing them in place, even throughout a disaster— through which they develop a unique insight into aging in place during a disaster. The purpose of this study was to identify individual and community-level support needs of older adults after a disaster through the lens of home-based care providers. Methods Using qualitative inquiry, five focus groups were conducted with home-based care providers (n = 25) who provided in-home care during Hurricane Irma and Hurricane Harvey. Participants were identified by contacting home health agencies listed in an open-source database of agencies participating in Centers for Medicare and Medicaid Services programs. Data were coded using an abductive analytic approach, and larger themes were generated in light of existing theory. Results The results were distilled into eight themes that related to the importance of community and family, informal and formal supports throughout the disaster management cycle, maintaining autonomy during a disaster, and institutional and systemic barriers to obtaining assistance. Conclusions In this study, home-based care providers described the challenges aging adults face in the response and recovery period after a large-scale disaster including maintaining continuity of care, encouraging individual preparedness, and accessing complex governmental support. Listening to home-based care providers offers new and important insights for developing interventions to address social and health needs for older adults aging in place after a large-scale disaster.