Older Adults' Process of Collaborating With a Support Team During Transitions From Hospital to Home: A Grounded Theory Study.

BACKGROUND AND OBJECTIVES: Little is known about how older adults engage with multiple sources of support and resources during transitions from hospital to home, a period of high vulnerability. This study aims to describe how older adults identify and collaborate with a support team, including unpaid/family caregivers, health care providers, and professional and social networks, during the transition. RESEARCH DESIGN AND METHODS: This study utilized grounded theory methodology. One-on-one interviews were conducted with adults aged 60 and older following their discharge from a medical/surgical inpatient unit in a large midwestern teaching hospital. Data were analyzed using open, axial, and selective coding. RESULTS: Participants (N = 25) ranged from 60 to 82 years of age, 11 were female, and all participants were White, non-Hispanic. They described a process of identifying a support team and collaborating with that team to manage at home and progress their health, mobility, and engagement. Support teams varied, but included collaborations between the older person, unpaid/family caregiver(s), and their health care providers. Their collaboration was impacted by the participant's professional and social networks. DISCUSSION AND IMPLICATIONS: Older adults collaborate with multiple sources of support and this collaboration is a dynamic process that varies across phases of their transition from hospital to home. Findings reveal opportunities for assessing individual's support and social networks, in addition to health and functional status, to determine needs and leverage resources during transitions in care.

A scoping review of unpaid caregivers' experiences during older adults' hospital-to-home transitions.

The objective of this scoping review is to examine current evidence regarding unpaid/family caregivers' experiences during older adults' hospital-to-home transitions to identify gaps and opportunities to involve caregivers in transitional care improvement efforts. Eligible articles focused on caregiver experience, outcomes, or interventions during older adults' hospital-to-home transitions. Our review identified several descriptive studies focused on exploring the caregiver experience of older adult hospital-to-home transitions and caregiver outcomes (such as preparedness, strain, burden, health, and well-being). Qualitative studies revealed challenges at multiple levels, including individual, interpersonal, and systemic. Few interventions have targeted or included caregivers to improve discharge education and address support needs during the transition. Future work should target underrepresented and marginalized groups of caregivers, and caregivers' collaboration with community-based services, social networks, or professional services. Work remains in developing and implementing interventions to support both older adult and caregiver needs.

miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells.

DC-SIGN+ monocyte-derived dendritic cells (mo-DCs) play important roles in bacterial infections and inflammatory diseases, but the factors regulating their differentiation and proinflammatory status remain poorly defined. Here, we identify a microRNA, miR-181a, and a molecular mechanism that simultaneously regulate the acquisition of DC-SIGN expression and the activation state of DC-SIGN+ mo-DCs. Specifically, we show that miR-181a promotes DC-SIGN expression during terminal mo-DC differentiation and limits its sensitivity and responsiveness to TLR triggering and CD40 ligation. Mechanistically, miR-181a sustains ERK-MAPK signaling in mo-DCs, thereby enabling the maintenance of high levels of DC-SIGN and a high activation threshold. Low miR-181a levels during mo-DC differentiation, induced by inflammatory signals, do not support the high phospho-ERK signal transduction required for DC-SIGNhi mo-DCs and lead to development of proinflammatory DC-SIGNlo/- mo-DCs. Collectively, our study demonstrates that high DC-SIGN expression levels and a high activation threshold in mo-DCs are linked and simultaneously maintained by miR-181a.

Loss of RAF kinase inhibitor protein is involved in myelomonocytic differentiation and aggravates RAS-driven myeloid leukemogenesis.

RAS-signaling mutations induce the myelomonocytic differentiation and proliferation of hematopoietic stem and progenitor cells. Moreover, they are important players in the development of myeloid neoplasias. RAF kinase inhibitor protein (RKIP) is a negative regulator of RAS-signaling. As RKIP loss has recently been described in RAS-mutated myelomonocytic acute myeloid leukemia, we now aimed to analyze its role in myelomonocytic differentiation and RAS-driven leukemogenesis. Therefore, we initially analyzed RKIP expression during human and murine hematopoietic differentiation and observed that it is high in hematopoietic stem and progenitor cells and lymphoid cells but decreases in cells belonging to the myeloid lineage. By employing short hairpin RNA knockdown experiments in CD34+ umbilical cord blood cells and the undifferentiated acute myeloid leukemia cell line HL-60, we show that RKIP loss is indeed functionally involved in myelomonocytic lineage commitment and drives the myelomonocytic differentiation of hematopoietic stem and progenitor cells. These results could be confirmed in vivo, where Rkip deletion induced a myelomonocytic differentiation bias in mice by amplifying the effects of granulocyte macrophage-colony-stimulating factor. We further show that RKIP is of relevance for RAS-driven myelomonocytic leukemogenesis by demonstrating that Rkip deletion aggravates the development of a myeloproliferative disease in NrasG12D -mutated mice. Mechanistically, we demonstrate that RKIP loss increases the activity of the RAS-MAPK/ERK signaling module. Finally, we prove the clinical relevance of these findings by showing that RKIP loss is a frequent event in chronic myelomonocytic leukemia, and that it co-occurs with RAS-signaling mutations. Taken together, these data establish RKIP as novel player in RAS-driven myeloid leukemogenesis.

Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP.

RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML are still unclear, we aimed to analyze the potential involvement of miRNAs within this study. miRNA microarray and qPCR data of more than 400 AML patient specimens revealed correlation between decreased expression of RKIP and increased expression of miR-23a, a member of the miR-23a/27a/24-2 cluster. In functional experiments, overexpression of miR-23a decreased RKIP mRNA and protein expression, whereas miR-23a inhibition caused the opposite effect. By using an RKIP 3'-untranslated region luciferase reporter construct with and without mutation or deletion of the putative miR-23a-binding site, we could show that RKIP modulation by miR-23a is mediated via direct binding to this region. Importantly, miR-23a overexpression induced a significant increase of proliferation in hematopoietic cells. Simultaneous transfection of an RKIP expression construct lacking the miR-23a-binding sites reversed this phenotype, indicating that this effect is truly mediated via downregulation of RKIP. Finally, by analyzing more than 4,300 primary patient specimens via database retrieval from The Cancer Genome Atlas, we could highlight the importance of the miR-23a/RKIP axis in a broad range of human cancer entities. In conclusion, we have identified miR-23a as a negative regulator of RKIP expression in AML and have provided data that suggest the importance of our observation beyond this tumor entity. Cancer Res; 76(12); 3644-54. ©2016 AACR.