Improving Nursing Home Disaster Readiness Through Implementation Science.

As large-scale disasters continue to become increasingly common worldwide, nursing homes, whose residents are more vulnerable to disaster-related health and psychosocial shocks, and their staff, are carrying progressively more responsibility for health care readiness practices. Implementation science is a research discipline that seeks to improve uptake of evidence-based practices, such as health care readiness planning, and thus has potential to improve nursing home care delivery during and after disasters. We describe the limited field of existing evidence-based strategies in the peer-reviewed literature that seek to advance health care readiness in the nursing home setting and illustrate how implementation science can better support health care readiness planning for nursing homes. We rest on 3 main themes: (1) implementation science frameworks can strengthen nursing home staff engagement around health care readiness; (2) implementation science can support tailoring of emergency preparedness plans to individual nursing homes' unique needs; and (3) implementation science can advance the integration of nursing homes into local, state, and federal health care readiness planning initiatives. Finally, research is urgently needed to both generate and disseminate implementation strategies that increase uptake of evidence-based health care readiness practices in the nursing home setting.

Home-Based Care Provider Perspectives on Care Refusal During the COVID-19 Pandemic.

Acute and chronic disease management continues to shift toward a health care in the home model, yet literature discussing continuity of home-based care services during public health emergencies, such as infectious disease pandemics, is scant. In the current study, we used semi-structured telephone interviews with 27 home-based care providers (HBCPs) from Medicare-certified home health care agencies located in eight U.S. counties to explore older adults' decision making around home-based care service continuation during the coronavirus disease 2019 (COVID-19) pandemic. Four themes emerged, including two related to older adults' decision making around refusal of in-home care and two related to HBCPs' responses to care refusals. Fear of COVID-19 infection motivated older adults to make care-related decisions that were incongruent with their health needs, including refusal of care in the home, despite receiving education from HBCPs. These data highlight a need for tools to help HBCPs better support patients through decision-making processes about care continuation during COVID-19 and future infectious disease pandemics. [Journal of Gerontological Nursing, 49(1), 35-41.].

Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-ß signalling.

Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is mostly unknown. Here we show that Eed deficiency in chondrocytes causes severe kyphosis and a growth defect with decreased chondrocyte proliferation, accelerated hypertrophic differentiation and cell death with reduced Hif1a expression. Eed deficiency also causes induction of multiple signalling pathways in chondrocytes. Wnt signalling overactivation is responsible for the accelerated hypertrophic differentiation and kyphosis, whereas the overactivation of TGF-ß signalling is responsible for the reduced proliferation and growth defect. Thus, our study demonstrates that PRC2 has an important regulatory role in lineage-committed tissue cells by suppressing overactivation of multiple signalling pathways.

EFFECT OF PREOPERATIVE PAIN AND DEPRESSIVE SYMPTOMS ON THE DEVELOPMENT OF POSTOPERATIVE DELIRIUM.

BACKGROUND: Preoperative pain and depression predispose patients to delirium. Our goal was to determine whether pain and depressive symptoms interact to increase delirium risk. METHODS: We enrolled 459 persons without dementia aged ≥70 years scheduled for elective orthopedic surgery. At baseline, participants reported their worst and average pain within seven days and current pain on a 0-10 scale. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale and chart. Delirium was assessed with the Confusion Assessment Method and chart. We examined the relationship between preoperative pain, depressive symptoms and delirium using multivariable analysis of pain and delirium stratified by presence of depressive symptoms. FINDINGS: Delirium, occurring in 23% of the sample, was significantly higher in those with depressive symptoms at baseline than those without (relative risk, RR, 1·6, 95% confidence interval, CI, 1·2-2·3). Preoperative pain was associated with an increased adjusted risk for delirium across all pain measures (RR from 1·07-1·08 per point of pain). In stratified analyses, patients with depressive symptoms had a 21% increased risk for delirium for each one-point increase in worst pain score, demonstrating a significant interaction (P=0·049). Similarly, a significant 13% increased risk for delirium was demonstrated for a one-point increase in average pain score, but the interaction did not achieve statistical significance. INTERPRETATION: Preoperative pain and depressive symptoms demonstrated increased risk for delirium independently and with substantial interaction, suggesting a cumulative impact. Thus, pain and depression are vulnerability factors for delirium that should be assessed before surgery. FUNDING: U.S. National Institute on Aging.

let-7 and miR-140 microRNAs coordinately regulate skeletal development.

MicroRNAs (miRNAs) play critical roles in multiple processes of skeletal development. A global reduction of miRNAs in growth plate chondrocytes results in defects in both proliferation and differentiation; however, specific microRNAs responsible for these defects have not been identified. In this study, we provide evidence that let-7 miRNAs and microRNA-140 (miR-140), among other miRNAs expressed in chondrocytes, play major roles in endochondral bone development. We overexpressed lin-28 homolog A (Lin28a) to inhibit let-7 miRNA biogenesis in growth plate chondrocytes. Lin28a overexpression efficiently and specifically reduced let-7 miRNAs and up-regulated let-7 target genes. However, unlike the previous notion that let-7 miRNAs inhibit proliferation and growth, suppression of let-7 miRNAs via Lin28a overexpression decreased proliferation in growth plate chondrocytes, likely through up-regulation of the let-7 target cell cycle regulators cell division cycle 34 (Cdc34) and E2F transcription factor 5 (E2F5). Deficiency of the chondrocyte-specific miRNA, miR-140, causes a differentiation defect in growth plate chondrocytes. Although either Lin28a overexpression or miR-140 deficiency alone caused only mild growth impairment, mice with both miR-140 deficiency and Lin28a overexpression in chondrocytes showed a dramatic growth defect. Deregulation of distinct processes in the absence of these miRNAs synergistically decreased the proliferating chondrocyte mass; miR-140 deficiency reduced differentiation into proliferating chondrocytes, whereas Lin28a overexpression decreased proliferation per se.

Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling.

MicroRNAs (miRNAs) play critical roles in a variety of biological processes in diverse organisms, including mammals. In the mouse skeletal system, a global reduction of miRNAs in chondrocytes causes a lethal skeletal dysplasia. However, little is known about the physiological roles of individual miRNAs in chondrocytes. The miRNA-encoding gene, Mir140, is evolutionarily conserved among vertebrates and is abundantly and almost exclusively expressed in chondrocytes. In this paper, we show that loss of Mir140 in mice causes growth defects of endochondral bones, resulting in dwarfism and craniofacial deformities. Endochondral bone development is mildly advanced due to accelerated hypertrophic differentiation of chondrocytes in Mir140-null mice. Comparison of profiles of RNA associated with Argonaute 2 (Ago2) between wild-type and Mir140-null chondrocytes identified Dnpep as a Mir140 target. As expected, Dnpep expression was increased in Mir140-null chondrocytes. Dnpep overexpression showed a mild antagonistic effect on bone morphogenetic protein (BMP) signaling at a position downstream of Smad activation. Mir140-null chondrocytes showed lower-than-normal basal BMP signaling, which was reversed by Dnpep knockdown. These results demonstrate that Mir140 is essential for normal endochondral bone development and suggest that the reduced BMP signaling caused by Dnpep upregulation plays a causal role in the skeletal defects of Mir140-null mice.