The Consequences of Unmet Needs for Assistance With Daily Life Activities Among Older Adults: A Systematic Review.

Many older adults are experiencing unmet needs for assistance with the activities of daily living (ADLs) and instrumental activities of daily living (IADLs). Such unmet needs might threaten their physical and psychosocial well-being. We conducted a systematic review to provide a comprehensive picture of the health consequences of unmet ADL/IADL needs among older adults. Twenty-eight published articles were included for qualitative synthesis. We found that unmet ADL/IADL needs were consistently associated with higher health care utilization (e.g., hospitalization, medical spending) and adverse psychosocial consequences (e.g., anxiety, depression), while the findings of falls and mortality remain inconsistent. More studies are needed to draw firm conclusions and to allow for quantitative synthesis. This review advocates for more coordinated and comprehensive long-term care services for older adults. Future studies should explore how the adverse health outcomes identified in this review can be prevented or improved by adequately meeting older adults' needs for assistance.

NT5DC2 knockdown suppresses progression, glycolysis, and neuropathic pain in triple-negative breast cancer by blocking the EGFR pathway.

Triple-negative breast cancer (TNBC) is an exceptionally aggressive breast cancer subtype associated with neuropathic pain. This study explores the effects of 5'-nucleotidase domain-containing protein 2 (NT5DC2) on the progression of TNBC and neuropathic pain. Microarray analysis was conducted to identify differentially expressed genes in TNBC and the pathways involved. Gain- and loss-of-function assays of NT5DC2 were performed in TNBC cells, followed by detection of the extracellular acidification rate, adenosine triphosphate (ATP) levels, lactic acid production, glucose uptake, proliferation, migration, and invasion in TNBC cells. Macrophages were co-cultured with TNBC cells to examine the release of polarization-related factors and cytokines. A xenograft tumor model was established for in vivo validation. In addition, a mouse model of neuropathic pain was established through subepineural injection of TNBC cells, followed by measurement of the sciatic functional index and behavioral analysis to assess neuropathic pain. NT5DC2 was upregulated in TNBC and was positively correlated with epidermal growth factor receptor (EGFR). NT5DC2 interacted with EGFR to promote downstream signal transduction in TNBC cells. NT5DC2 knockdown diminished proliferation, migration, invasion, the extracellular acidification rate, ATP levels, lactic acid production, and glucose uptake in TNBC cells. Co-culture with NT5DC2-knockdown TNBC cells alleviated the M2 polarization of macrophages. Furthermore, NT5DC2 knockdown reduced tumor growth and neuropathic pain in mice. Importantly, activation of the EGFR pathway counteracted the effects of NT5DC2 knockdown. NT5DC2 knockdown protected against TNBC progression and neuropathic pain by inactivating the EGFR pathway.

Regulatory NK1.1-CD4+NKG2D+ subset induced by NKG2DL+ cells promotes tumor evasion in mice.

Regulatory T cells play critical roles in self-tolerance and tumor evasion. CD4+NKG2D+ cells with regulatory activity are present in patients with NKG2DL+ tumors and juvenile systemic lupus erythematosus. We previously showed that TGF-ß-producing CD4+NKG2D+ T cells are present in pCD86-Rae-1ε transgenic mice. Here, we performed both ex vivo and in vivo studies on pCD86-Rae-1ε transgenic mice and an MC38 tumor-bearing mouse model and show that NK1.1-CD4+NKG2D+ T cells have regulatory activity in pCD86-Rae-1ε transgenic mice. Furthermore, this T-cell subset was induced in mice transplanted with NKG2DL+ tumor cells and produced TGF-ß and FasL, and secreted low amounts of IFN-γ. This T-cell subset downregulated the function of effector T cells and dendritic cells, which were abolished by anti-TGF-ß antibody. In vivo, adoptive transfer of NK1.1-CD4+NKG2D+ T cells promoted TGF-ß-dependent tumor growth in mice. We further found that ex vivo induction of NK1.1-CD4+NKG2D+ T cells was dependent on both anti-CD3 and NKG2DL stimulation. Furthermore, regulatory NK1.1-CD4+NKG2D+ T cells did not express Foxp3 or CD25 and expressed intermediate levels of T-bet. Western-blotting showed that STAT3 signaling was activated in NK1.1-CD4+NKG2D+ T cells of MC38 tumor-bearing and pCD86-Rae-1ε transgenic mice. In conclusion, we describe a regulatory NK1.1-CD4+NKG2D+ T-cell population, different from other regulatory T cells and abnormally elevated in pCD86-Rae-1ε transgenic and MC38 tumor-bearing mice.

NK1.1- CD4+ NKG2D+ T cells suppress DSS-induced colitis in mice through production of TGF-ß.

CD4+ NKG2D+ T cells are associated with tumour, infection and autoimmune diseases. Some CD4+ NKG2D+ T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-ß and FasL to facilitate tumour evasion. Here, murine CD4+ NKG2D+ T cells were further classified into NK1.1- CD4+ NKG2D+ and NK1.1+ CD4+ NKG2D+ subpopulations. The frequency of NK1.1- CD4+ NKG2D+ cells decreased in inflamed colons, whereas more NK1.1+ CD4+ NKG2D+ cells infiltrated into colons of mice with DSS-induced colitis. NK1.1- CD4+ NKG2D+ cells expressed TGF-ß and FasL without secreting IFN-γ, IL-21 and IL-17 and displayed no cytotoxicity. The adoptive transfer of NK1.1- CD4+ NKG2D+ cells suppressed DSS-induced colitis largely dependent on TGF-ß. NK1.1- CD4+ NKG2D+ cells did not expressed Foxp3, CD223 (LAG-3) and GITR. The subpopulation was distinct from NK1.1+ CD4+ NKG2D+ cells in terms of surface markers and RNA transcription. NK1.1- CD4+ NKG2D+ cells also differed from Th2 or Th17 cells because the former did not express GATA-3 and ROR-γt. Thus, NK1.1- CD4+ NKG2D+ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.