The role of outdoor microclimatic features at long-term care facilities in advancing the health of its residents: An integrative review and future strategies.

Projections show that Earth's climate will continue to warm concurrent with increases in the percentage of the world's elderly population. With an understanding that the body's resilience to the heat degrades as it ages, these coupled phenomena point to serious concerns of heat-related mortality in growing elderly populations. As many of the people in this age cohort choose to live in managed long-term care facilities, it's imperative that outdoor spaces of these communities be made thermally comfortable so that connections with nature and the promotion of non-sedentary activities are maintained. Studies have shown that simply being outside has a positive impact on a broad range of the psychosocial well-being of older adults. However, these spaces must be designed to afford accessibility, safety, and aesthetically pleasing experiences so that they are taken full advantage of. Here, we employ an integrative review to link ideas from the disciplines of climate science, health and physiology, and landscape architecture to explain the connections between heat, increased morbidity and mortality in aging adults, existing gaps in thermal comfort models, and key strategies in the development of useable, comfortable outdoor spaces for older adults. Integrative reviews allow for new frameworks or perspectives on a subject to be introduced. Uncovering the synergy of these three knowledge bases can contribute to guiding microclimatic research, design practitioners, and care providers as they seek safe, comfortable and inviting outdoor spaces for aging adults.

Frailty Resilience Score: A Novel Measure of Frailty Resilience Associated With Protection From Frailty and Survival.

Frailty is characterized by increased vulnerability to disability and high risk for mortality in older adults. Identification of factors that contribute to frailty resilience is an important step in the development of effective therapies that protect against frailty. First, a reliable quantification of frailty resilience is needed. We developed a novel measure of frailty resilience, the Frailty Resilience Score (FRS), that integrates frailty genetic risk, age, and sex. Application of FRS to the LonGenity cohort (n = 467, mean age 74.4) demonstrated its validity compared to phenotypic frailty and its utility as a reliable predictor of overall survival. In a multivariable-adjusted analysis, 1-standard deviation increase in FRS predicted a 38% reduction in the hazard of mortality, independent of baseline frailty (p < .001). Additionally, FRS was used to identify a proteomic profile of frailty resilience. FRS was shown to be a reliable measure of frailty resilience that can be applied to biological studies of resilience.

Heparan sulfate Ndst1 regulates vascular smooth muscle cell proliferation, vessel size and vascular remodeling.

Heparan sulfate proteoglycans are abundant molecules in the extracellular matrix and at the cell surface. Heparan sulfate chains are composed of groups of disaccharides whose side chains are modified through a series of enzymatic reactions. Deletion of these enzymes alters heparan sulfate fine structure and leads to changes in cell proliferation and tissue development. The role of heparan sulfate modification has not been explored in the vessel wall. The goal of this study was to test the hypothesis that altering heparan sulfate fine structure would impact vascular smooth muscle cell (VSMC) proliferation, vessel structure, and remodeling in response to injury. A heparan sulfate modifying enzyme, N-deacetylase N-sulfotransferase1 (Ndst1) was deleted in smooth muscle resulting in decreased N- and 2-O sulfation of the heparan sulfate chains. Smooth muscle specific deletion of Ndst1 led to a decrease in proliferating VSMCs and the circumference of the femoral artery in neonatal and adult mice. In response to vascular injury, mice lacking Ndst1 exhibited a significant reduction in lesion formation. Taken together, these data provide new evidence that modification of heparan sulfate fine structure through deletion of Ndst1 is sufficient to decrease VSMC proliferation and alter vascular remodeling.

Coronary Microvascular Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Artery Disease Is Associated With Elevated Serum Homocysteine Levels.

Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (<40% angiographic stenosis), who underwent CMED evaluation with functional angiography and had serum homocysteine levels measured. Patients were classified as having normal microvascular function versus CMED. Patients in the CMED group (n=743; 52%) had higher mean age (52.1±12.2 versus 50.0±12.4 years; P<0.0001), higher body mass index (29.1 [25.0-32.8] versus 27.5 [24.2-32.4]; P=0.001), diabetes mellitus (12.5% versus 9.4%; P=0.03), and fewer women (63.5% versus 68.7%; P=0.04) compared with patients in the normal microvascular function group. However, they had lower rates of smoking history, and mildly lower low-density lipoprotein cholesterol levels. Serum homocysteine levels were significantly higher in patients with CMED, and the highest quartile of serum homocysteine level (>9 µmol/L) was an independent predictor of CMED (odds ratio, 1.34 [95% CI, 1.03-1.75]; P=0.03) after adjustment for age; sex; body mass index; chronic kidney disease (CKD); diabetes mellitus; smoking exposure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol and triglycerides; and aspirin, statin, and B vitamin use. Conclusions Patients with CMED have significantly higher levels of serum homocysteine. Elevated serum homocysteine levels were associated with a significantly increased odds of an invasive diagnosis of CMED. The current study supports a potential role for homocysteine for diagnosis and target treatment in the patients with early coronary atherosclerosis.

Elevated plasma homocysteine levels are associated with impaired peripheral microvascular vasomotor response.

BACKGROUND: Hyperhomocysteinemia (HHcy) has been proposed as an important cardiovascular risk factor (cRF). However, little is known about the association between plasma homocysteine levels and peripheral microvascular endothelial dysfunction (PMED), which is an integrated index of vascular health. METHODS: This cross-sectional and retrospective cohort study included patients who underwent non-invasive PMED assessment using reactive hyperemia peripheral arterial tonometry (RH-PAT). The association between HHcy and PMED, and its impact on MACE (all-cause mortality and atherosclerotic cardiovascular events) was investigated. RESULTS: A total of 257 patients were enrolled (HHcy > 10.0 µmol/L, N = 51; lower levels of homocysteine [LHcy] ≤ 10 µmol/L, N = 206). Patients with HHcy were older, predominantly males, and with more comorbidities than patients with LHcy (p < 0.05 for all). RH-PAT index was lower in patients with HHcy versus LHcy (p = 0.01). A significant association between HHcy and PMED was observed in older (≥60 years), obese (≥30 kg/m2), present/past smokers and hypertensive patients. HHcy was significantly associated with PMED even after adjusting for other cRF and B-vitamins supplementation. HHcy was associated with an increased risk of MACE with a hazard ratio of 3.65 (95% CI 1.41-9.48, p = 0.01) and an adjusted hazard ratio of 2.44 (95% CI 0.91-6.51, p = 0.08) after adjustment for age (≥60 years). CONCLUSION: HHcy was independently associated with PMED after adjusting for cRF and B-vitamins supplementation. Thus, the link between homocysteine and MACE could be mediated by endothelial dysfunction, and will require further clarification with future studies.

Oxytocin and cancer: An emerging link.

The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research suggests that oxytocin effects may depend on cell type, concentration of the hormone, its interactions with other hormones in the microenvironment, and the precise localization of its receptor on the cell membrane. Future research is needed to further elucidate the involvement of oxytocin in cancer, and whether it could be a clinical cancer biomarker or therapeutic target.

Changes in expression of proteoglycan core proteins and heparan sulfate enzymes in the developing and adult murine aorta.

Proteoglycan core proteins are linked to four different classes of linear sugar chains referred to as glycosaminoglycans. Heparan sulfate constitutes one of these classes of glycosaminoglycans, and has been shown to be important in developmental processes as well as disease. We designed a low-density gene expression array to identify expression levels of heparan sulfate biosynthetic enzymes and proteoglycan core proteins in the aorta of late stage embryos (E18.5) and adult mice (12 weeks). Significant changes were found in mRNA expression of proteoglycan core proteins syndecan, glypican, decorin, perlecan, and versican from development to adulthood (n = 8, p < 0.05). Immunohistochemistry revealed a striking localization of both decorin and perlecan staining to the subendothelium in adult vessels, which differed from consistent staining of the endothelium, smooth muscle, and adventitia in development. Significant differences were also identified in the expression of the heparan sulfate modifying enzymes, glururonyl C5 epimerase, 2-O and 6-O sulfotransferases, and N-deacetylase/N sulfotransferases 1-3 (n = 8, p < 0.05). In conclusion, proteoglycan core proteins and heparan sulfate biosynthetic enzymes in the aorta undergo significant changes in their expression from development to adulthood. These findings may have important biological significance in the specific cell-defined roles of proteoglycan and heparan sulfate related targets in vascular development, maintenance, and response to various perturbations.