AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against ischemic memory improving cutaneous wound healing.

Peripheral vasculopathies cause severe wound hypoxia inducing the hypoxamiR miR-210. High level of miR-210, persisting in wound-edge tissue as ischemic memory, suppresses oxidative metabolism and inhibits cell proliferation necessary for healing. In wound-edge tissue of chronic wound patients, elevated miR-210 was tightly associated with inhibition of epidermal cell proliferation as evident by lowered Ki67 immunoreactivity. To inhibit miR-210 in murine ischemic wound-edge tissue, we report the formulation of antihypoxamiR functionalized gramicidin lipid nanoparticles (AFGLN). A single intradermal delivery of AFGLN encapsulating LNA-conjugated anti-hypoximiR-210 (AFGLNmiR-210) lowered miR-210 level in the ischemic wound-edge tissue. In repTOP™mitoIRE mice, AFGLNmiR-210 rescued keratinocyte proliferation as visualized by in vivo imaging system (IVIS). 31P NMR studies showed elevated ATP content at the ischemic wound-edge tissue following AFGLNmiR-210 treatment indicating recovering bioenergetics necessary for healing. Consistently, AFGLNmiR-210 improved ischemic wound closure. The nanoparticle based approach reported herein is effective for miR-directed wound therapeutics warranting further translational development.

Factors Associated with Outdoor Winter Walking in Older Adults: A Scoping Review.

The purpose of this study was to identify internal and external factors associated with outdoor winter walking in older adults. In this scoping review, 12 databases were searched. Inclusion criteria included English language, focus on adults 65 years of age or older, and evaluation of factors associated with outdoor winter walking. Two authors screened titles/abstracts and full text. Conflicts were resolved by consensus. Data were extracted, organized into tables, and summarized as pertaining to barriers/facilitators and internal/external factors associated with outdoor winter walking. A total of 6,843 articles were identified, 1,898 duplicates were removed, 4,789 were excluded during title/abstract screening, and 148 were excluded during full-text review. Eight studies were included. Four categories of factors affecting outdoor winter walking in older adults were identified: adverse weather conditions, physical environment, physical function, and perceptions relating to winter walking conditions. Rehabilitation and exercise professionals can use the results to educate their clients and implement the facilitators of and alternatives and solutions to barriers to outdoor winter walking.

Use of Mammalian Target of Rapamycin Inhibitors for Pancreas Transplant Immunosuppression Is Associated With Improved Allograft Survival and Improved Early Patient Survival.

OBJECTIVES: Mammalian targets of rapamycin inhibitors (mTORi) are considered second-line immunosuppression agents because of associated increases in rejection and impaired wound healing. Recent reports indicate mTORi have been linked to improved survival, decreased inflammatory response in pancreatitis, and antiproliferative and antiangiogenic activity. Mammalian targets of rapamycin inhibitors have not been extensively analyzed in pancreas transplant recipients. METHODS: Adults with pancreas and kidney-pancreas transplants from 1987 to 2016 in the United Network for Organ Sharing database were analyzed (N = 25,837). Subjects were stratified into 2 groups: use of mTORi (n = 4174) and use of non-mTORi-based immunosuppression (n = 21,663). The log-rank test compared survival rates. Univariate and multivariate Cox regression analyses assessed patient and graft survival. RESULTS: Mammalian targets of rapamycin inhibitors were associated with a 7% risk reduction in allograft failure (hazard ratio, 0.931; P = 0.006). Allograft survival rates were significantly different between mTORi versus non-mTORi (P < 0.0001).The mTORi group showed a significantly higher patient survival rate 1, 3, 5, and 10 years posttransplant compared. Patient survival at 15 years was not significantly different. CONCLUSIONS: The use of mTORi for immunosuppression in pancreas transplant is associated with improved allograft survival and early patient survival posttransplant (up to 10 years).

Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue.

Although cellular therapies represent a promising strategy for a number of conditions, current approaches face major translational hurdles, including limited cell sources and the need for cumbersome pre-processing steps (for example, isolation, induced pluripotency). In vivo cell reprogramming has the potential to enable more-effective cell-based therapies by using readily available cell sources (for example, fibroblasts) and circumventing the need for ex vivo pre-processing. Existing reprogramming methodologies, however, are fraught with caveats, including a heavy reliance on viral transfection. Moreover, capsid size constraints and/or the stochastic nature of status quo approaches (viral and non-viral) pose additional limitations, thus highlighting the need for safer and more deterministic in vivo reprogramming methods. Here, we report a novel yet simple-to-implement non-viral approach to topically reprogram tissues through a nanochannelled device validated with well-established and newly developed reprogramming models of induced neurons and endothelium, respectively. We demonstrate the simplicity and utility of this approach by rescuing necrotizing tissues and whole limbs using two murine models of injury-induced ischaemia.