Greatly enhanced risk to humans as a consequence of empirically determined lower moist heat stress tolerance.

As heatwaves become more frequent, intense, and longer-lasting due to climate change, the question of breaching thermal limits becomes pressing. A wet-bulb temperature (Tw) of 35 °C has been proposed as a theoretical upper limit on human abilities to biologically thermoregulate. But, recent-empirical-research using human subjects found a significantly lower maximum Tw at which thermoregulation is possible even with minimal metabolic activity. Projecting future exposure to this empirical critical environmental limit has not been done. Here, using this more accurate threshold and the latest coupled climate model results, we quantify exposure to dangerous, potentially lethal heat for future climates at various global warming levels. We find that humanity is more vulnerable to moist heat stress than previously proposed because of these lower thermal limits. Still, limiting warming to under 2 °C nearly eliminates exposure and risk of widespread uncompensable moist heatwaves as a sharp rise in exposure occurs at 3 °C of warming. Parts of the Middle East and the Indus River Valley experience brief exceedances with only 1.5 °C warming. More widespread, but brief, dangerous heat stress occurs in a +2 °C climate, including in eastern China and sub-Saharan Africa, while the US Midwest emerges as a moist heat stress hotspot in a +3 °C climate. In the future, moist heat extremes will lie outside the bounds of past human experience and beyond current heat mitigation strategies for billions of people. While some physiological adaptation from the thresholds described here is possible, additional behavioral, cultural, and technical adaptation will be required to maintain healthy lifestyles.

Human scalp hair as a thermoregulatory adaptation.

Humans are unique among mammals in having a functionally naked body with a hair-covered scalp. Scalp hair is exceptionally variable across populations within Homo sapiens. Neither the function of human scalp hair nor the consequences of variation in its morphology have been studied within an evolutionary framework. A thermoregulatory role for human scalp hair has been previously suggested. Here, we present experimental evidence on the potential evolutionary function of human scalp hair and variation in its morphology. Using a thermal manikin and human hair wigs at different wind speeds in a temperature and humidity-controlled environment, with and without simulated solar radiation, we collected data on the convective, radiative, and evaporative heat fluxes to and from the scalp in relation to properties of a range of hair morphologies, as well as a naked scalp. We find evidence for a significant reduction in solar radiation influx to the scalp in the presence of hair. Maximal evaporative heat loss potential from the scalp is reduced by the presence of hair, but the amount of sweat required on the scalp to balance the incoming solar heat (i.e., zero heat gain) is reduced in the presence of hair. Particularly, we find that hair that is more tightly curled offers increased protection against heat gain from solar radiation.

Sex differences in heat stress vulnerability among middle-aged and older adults (PSU HEAT Project).

Individuals over the age of 65 yr are the most vulnerable population during severe environmental heat events, experiencing worse health outcomes than any other age cohort. The risk is greater in older women than in age-matched men; however, whether that reflects a greater susceptibility to heat in women, or simply population sex proportionality, is unclear. Seventy-two participants (29 M/43 F) aged 40-92 yr were exposed to progressive heat stress at a metabolic rate designed to reflect activities of daily living. Experiments were conducted in both hot-dry (HD; up to 53°C; ≤25% rh) and warm-humid (WH; ∼35°C; ≥50% rh) environments. After critical limits were determined for each condition, forward stepwise multiple linear regression analyses were conducted with net metabolic rate (Mnet) and age entered into the model first, followed by sex, body mass (mb), maximal oxygen consumption (V̇o2max), body surface area, and LDL cholesterol. After accounting for Mnet and age, sex further improved the regression model in the HD environment ([Formula: see text] = 0.34, P < 0.001) and the WH environment ([Formula: see text] = 0.36, P < 0.005). Sex explained ∼15% of the variance in critical environmental limits in HD conditions and 12% in WH conditions. Heat compensability curves were shifted leftward for older women, indicating age- and sex-dependent heat vulnerability compared with middle-aged women and older men in WH (P = 0.007, P = 0.03) and HD (P = 0.001, P = 0.01) environments. This reflects the heterogeneity of thermal-balance thresholds associated with aging relative to those seen in young adults and suggests that older females are more vulnerable than their age-matched male counterparts.NEW & NOTEWORTHY In contrast to young adults, there are sex differences in critical environmental limits in middle-aged and older adults. Older women exhibit lower critical environmental limits in both humid and dry extreme environments demonstrated by a leftward shift in heat compensability curves. These data confirm a true sex difference in heat vulnerability of older adults and support the epidemiological mortality data from environmental heat waves.

A Novel Conceptual Model for Human Heat Tolerance.

Human "heat tolerance" has no accepted definition or physiological underpinnings; rather, it is almost always discussed in relative or comparative terms. We propose to use environmental limits to heat balance accounting for metabolic rate and clothing, that is, the environments for which heat stress becomes uncompensable for a specified metabolic rate and clothing, as a novel metric for quantifying heat tolerance.

Adverse heat-health outcomes and critical environmental limits (Pennsylvania State University Human Environmental Age Thresholds project).

BACKGROUND: The earth's climate is warming and the frequency, duration, and severity of heat waves are increasing. Meanwhile, the world's population is rapidly aging. Epidemiological data demonstrate exponentially greater increases in morbidity and mortality during heat waves in adults ≥65 years. Laboratory data substantiate the mechanistic underpinnings of age-associated differences in thermoregulatory function. However, the specific combinations of environmental conditions (i.e., ambient temperature and absolute/relative humidity) above which older adults are at increased risk of heat-related morbidity and mortality are less clear. METHODS: This review was conducted to (1) examine the recent (past 3 years) literature regarding heat-related morbidity and mortality in the elderly and discuss projections of future heat-related morbidity and mortality based on climate model data, and (2) detail the background and unique methodology of our ongoing laboratory-based projects aimed toward identifying the specific environmental conditions that result in elevated risk of heat illness in older adults, and the implications of using the data toward the development of evidence-based safety interventions in a continually-warming climate (PSU HEAT; Human Environmental Age Thresholds). RESULTS: The recent literature demonstrates that extreme heat continues to be increasingly detrimental to the health of the elderly and that this is apparent across the world, although the specific environmental conditions above which older adults are at increased risk of heat-related morbidity and mortality remain unclear. CONCLUSION: Characterizing the environmental conditions above which risk of heat-related illnesses increase remains critical to enact policy decisions and mitigation efforts to protect vulnerable people during extreme heat events.

Skin pigmentation is negatively associated with circulating vitamin D concentration and cutaneous microvascular endothelial function.

Darkly pigmented individuals are at the greatest risk of hypovitaminosis D, which may result in microvascular endothelial dysfunction via reduced nitric oxide (NO) bioavailability and/or increased oxidative stress and inflammation. We investigated the associations among skin pigmentation (M-index; skin reflectance spectrophotometry), serum vitamin D concentration [25(OH)D], circulating inflammatory cytokine (TNF-α, IL-6, and IL-10) concentrations, and the NO contribution to local heating-induced cutaneous vasodilation (%NO-mediated vasodilation) in a diversely pigmented cohort of young adults. An intradermal microdialysis fiber was placed in the forearms of 33 healthy adults (14 men/19 women; 18-27 yr; M-index, 30-81 AU) for local delivery of pharmacological agents. Lactated Ringer's solution was perfused through the fiber during local heating-induced (39°C) cutaneous vasodilation. After attaining stable elevated blood flow, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibiter) was infused to quantify %NO-mediated vasodilation. Red cell flux was measured (laser-Doppler flowmetry; LDF) and cutaneous vascular conductance (CVC = LDF/MAP) was normalized to maximal (%CVCmax; 28 mM sodium nitroprusside + 43°C). Serum [25(OH)D] and circulating cytokines were analyzed by ELISA and multiplex assay, respectively. M-index was negatively associated with [25(OH)D] (r = -0.57, P < 0.0001) and %NO-mediated vasodilation (r = -0.42, P = 0.02). Serum[25(OH)D] was positively related to %NO (r = 0.41, P = 0.02). Controlling for [25(OH)D] weakened the association between M-index and %NO-mediated dilation (P = 0.16, r = -0.26). There was a negative curvilinear relation between [25(OH)D] and circulating IL-6 (r = -0.56, P < 0.001), but not TNF-α or IL-10 (P ≥ 0.14). IL-6 was not associated with %NO-mediated vasodilation (P = 0.44). These data suggest that vitamin D insufficiency/deficiency may contribute to reduced microvascular endothelial function in healthy, darkly pigmented young adults.NEW & NOTEWORTHY Endothelial dysfunction, an antecedent to hypertension and overt CVD, is commonly observed in otherwise healthy Black adults, although the underlying causes remain unclear. We show that reduced vitamin D availability with increasing degrees of skin pigmentation is associated with reduced microvascular endothelial function, independent of race or ethnicity, in healthy young adults. Greater prevalence of vitamin D deficiency in more darkly pigmented individuals may predispose them to increased risk of endothelial dysfunction.

Cross-cultural variation in thirst perception in hot-humid and hot-arid environments: Evidence from two small-scale populations.

OBJECTIVES: Thirst is an evolved central homeostatic feedback system that helps regulate body water for survival. Little research has examined how early development and exposure to extreme environments and water availability affect thirst perception, particularly outside Western settings. Therefore, we compared two indicators of perceived thirst (current thirst and pleasantness of drinking water) using visual scales among Tsimane' forager-horticulturalists in the hot-humid Bolivian Amazon and Daasanach agro-pastoralists in hot-arid Northern Kenya. METHODS: We examined how these measures of perceived thirst were associated with hydration status (urine specific gravity), ambient temperatures, birth season, age, and population-specific characteristics for 607 adults (n = 378 Tsimane', n = 229 Daasanach) aged 18+ using multi-level mixed-effect regressions. RESULTS: Tsimane' had higher perceived thirst than Daasanach. Across populations, hydration status was unrelated to both measures of thirst. There was a significant interaction between birth season and temperature on pleasantness of drinking water, driven by Kenya data. Daasanach born in the wet season (in utero during less water availability) had blunted pleasantness of drinking water at higher temperatures compared to those born in the dry season (in utero during greater water availability). CONCLUSIONS: Our findings suggest hydration status is not a reliable predictor of thirst perceptions in extreme-hot environments with ad libitum drinking. Rather, our findings, which require additional confirmation, point to the importance of water availability during gestation in affecting thirst sensitivity to heat and water feedback mechanisms, particularly in arid environments. Thirst regulation will be increasingly important to understand given climate change driven exposures to extreme heat and water insecurity.

Utility of the Heat Index in defining the upper limits of thermal balance during light physical activity (PSU HEAT Project).

Extreme heat events and consequent detrimental heat-health outcomes have been increasing in recent decades and are expected to continue with future climate warming. While many indices have been created to quantify the combined atmospheric contributions to heat, few have been validated to determine how index-defined heat conditions impact human health. However, this subset of indices is likely not valid for all situations and populations nor easily understood and interpreted by health officials and the public. In this study, we compare the ability of thresholds determined from the National Weather Service's (NWS) Heat Index (HI), the Wet Bulb Globe Temperature (WBGT), and the Universal Thermal Climate Index (UTCI) to predict the compensability of human heat stress (upper limits of heat balance) measured as part of the Pennsylvania State University's Heat Environmental Age Thresholds (PSU HEAT) project. While the WBGT performed the best of the three indices for both minimal activities of daily living (MinAct; 83 W·m-2) and light ambulation (LightAmb; 133 W·m-2) in a cohort of young, healthy subjects, HI was likewise accurate in predicting heat stress compensability in MinAct conditions. HI was significantly correlated with subjects' perception of temperature and humidity as well as their body core temperature, linking perception of the ambient environment with physiological responses in MinAct conditions. Given the familiarity the public has with HI, it may be better utilized in the expansion of safeguard policies and the issuance of heat warnings during extreme heat events, especially when access to engineered cooling strategies is unavailable.

Heat exposure limits for young unacclimatized males and females at low and high humidity.

Little is known about the separate and combined influences of humidity conditions, sex, and aerobic fitness on heat tolerance in unacclimatized males and females. The purpose of the current study was to describe heat tolerance, in terms of critical WBGT (WBGTcrit), in unacclimatized young males and females in hot-dry (HD) and warm-humid (WH) environments. Eighteen subjects (9 M/9F; 21 ± 2 yr) were tested during exercise at 30% V̇O2max in a controlled environmental chamber. Progressive heat stress exposures were performed with either (1) constant dry-bulb temperature (Tdb) of 34 and 36 °C and increasing ambient water vapor pressure (Pa) (Pcrit trials; WH); or (2) constant Pa of 12 and 16 mmHg and increasing Tdb (Tcrit trials; HD). Chamber Tdb and Pa, and subject esophageal temperature (Tes), were continuously monitored throughout each trial. After a 30-min equilibration period, progressive heat stress continued until subject heat balance could no longer be maintained and a clear rise in Tes was observed. Absolute WBGTcrit and WBGTcrit adjusted to a metabolic rate of 300 W (WBGT300), and the difference between WBGTcrit and occupational exposure limits (OEL; ΔOEL) was assessed. WBGTcrit, WBGT300, and ΔOEL were higher in WH compared to HD (p < 0.0001) for females but were the same between environments for males (p ≥ 0.21). WBGTcrit was higher in females compared to males in WH (p < 0.0001) but was similar between sexes in HD (p = 0.44). When controlling for metabolic rate, WBGT300 and ΔOEL were higher in males compared to females in WH and HD (both p < 0.0001). When controlling for sex, V̇O2max was not associated with WBGT300 or ΔOEL for either sex (r ≤ 0.12, p ≥ 0.49). These findings suggest that WBGTcrit is higher in females compared to males in WH, but not HD, conditions. Additionally, the WBGTcrit is lower in females, but not males, in HD compared to WH conditions.

Metabolism- and sex-dependent critical WBGT limits at rest and during exercise in the heat.

Critical environmental limits are environmental thresholds above which heat gain exceeds heat loss and body core temperature (Tc) cannot be maintained at equilibrium. Those limits can be represented as critical wet-bulb globe temperature (WBGTcrit), a validated index that represents the overall thermal environment. Little is known about WBGTcrit at rest and during low-to-moderate intensity exercise, or sex differences in WBGTcrit, in unacclimated young adults. The following hypotheses were tested: 1) WBGTcrit progressively decreases as metabolic heat production (Mnet) increases, 2) no sex differences in WBGTcrit occur at rest, and 3) WBGTcrit is lower during absolute-intensity exercise but higher at relative intensities in women than in men. Thirty-six participants [19 men (M)/17 women (W); 23 ± 4 yr] were tested at rest, during light, absolute-intensity exercise (10 W), or during moderate, relative-intensity exercise [30% maximal oxygen consumption (V̇o2max)] in an environmental chamber. Dry-bulb temperature was clamped as relative humidity or ambient water vapor pressure was increased until an upward inflection was observed in Tc (rectal or esophageal temperature). Sex-aggregated WBGTcrit was lower during 10 W (32.9°C ± 1.7°C, P < 0.0001) and 30% V̇o2max (31.6°C ± 1.1°C, P < 0.0001) exercise versus at rest (35.3°C ± 0.8°C), and lower at 30% V̇o2max versus 10 W (P = 0.01). WBGTcrit was similar between sexes at rest (35.6°C ± 0.8°C vs. 35.0°C ± 0.8°C, P = 0.83), but lower during 10 W (31.9°C ± 1.7°C vs. 34.1°C ± 0.3°C, P < 0.01) and higher during 30% V̇o2max (32.4°C ± 0.8°C vs. 30.8°C ± 0.9°C, P = 0.03) exercise in women versus men. These findings suggest that WBGTcrit decreases as Mnet increases, no sex differences occur in WBGTcrit at rest, and sex differences in WBGTcrit during exercise depend on absolute versus relative intensities.

Skin pigmentation and vitamin D-folate interactions in vascular function: an update.

PURPOSE OF REVIEW: Vitamin D and folate promote vascular endothelial health and may therefore help mitigate the development of cardiovascular disease (CVD). Ultraviolet radiation (UVR) exposure stimulates cutaneous vitamin D synthesis but degrades the bioactive metabolite of folate, 5-methyltetrahydrofolate (5-MTHF). Skin melanin absorbs UVR, thereby modulating the impact of UVR exposure on vitamin D and 5-MTHF metabolism. This review presents recent findings regarding the inter-relations among UVR, skin pigmentation, folate and vitamin D, and endothelial function. RECENT FINDINGS: Evidence for roles of folic acid or vitamin D supplementation on CVD endpoints is inconsistent, although preclinical and clinical studies have demonstrated the efficacy of both micronutrients for improving endothelial function. Vitamin D deficiency is most prevalent in darkly pigmented individuals living in relatively low-UVR environments. Conversely, there is a negative relation between accumulated UVR exposure and serum folate concentration in lightly pigmented adults. The interactions among UVR and bioavailable folate and vitamin D differentially impact endothelial function in differently pigmented skin. SUMMARY: UVR exposure disparately impacts folate and vitamin D metabolism in differently pigmented skin depending upon regional UVR intensity and seasonality. These findings present new clinical research questions regarding the interactions among UVR, skin pigmentation, folate and vitamin D bioavailability, and endothelial health.

Hydration in relation to water insecurity, heat index, and lactation status in two small-scale populations in hot-humid and hot-arid environments.

OBJECTIVES: This study compared the prevalence of concentrated urine (urine specific gravity ≥1.021), an indicator of hypohydration, across Tsimane' hunter-forager-horticulturalists living in hot-humid lowland Bolivia and Daasanach agropastoralists living in hot-arid Northern Kenya. It tested the hypotheses that household water and food insecurity would be associated with higher odds of hypohydration. METHODS: This study collected spot urine samples and corresponding weather data along with data on household water and food insecurity, demographics, and health characteristics among 266 Tsimane' households (N = 224 men, 235 women, 219 children) and 136 Daasanach households (N = 107 men, 120 women, 102 children). RESULTS: The prevalence of hypohydration among Tsimane' men (50.0%) and women (54.0%) was substantially higher (P < .001) than for Daasanach men (15.9%) and women (17.5%); the prevalence of hypohydration among Tsimane' (37.0%) and Daasanach (31.4%) children was not significantly different (P = .33). Multiple logistic regression models suggested positive but not statistically significant trends between household water insecurity and odds of hypohydration within populations, yet some significant joint effects of water and food insecurity were observed. Heat index (2°C) was associated with a 23% (95% confidence interval [CI]: 1.09-1.40, P = .001), 34% (95% CI: 1.18-1.53, P < .0005), and 23% (95% CI: 1.04-1.44, P = .01) higher odds of hypohydration among Tsimane' men, women, and children, respectively, and a 48% (95% CI: 1.02-2.15, P = .04) increase in the odds among Daasanach women. Lactation status was also associated with hypohydration among Tsimane' women (odds ratio = 3.35, 95% CI: 1.62-6.95, P = .001). CONCLUSION: These results suggest that heat stress and reproductive status may have a greater impact on hydration status than water insecurity across diverse ecological contexts.

Examining "race" in physiology.

Racial disparities in cardiovascular and cerebrovascular health outcomes are well described, and recent research has shed light on the mechanistic underpinnings of those disparities. However, "race" is a social construct that is poorly defined and continually evolving and is historically based on faulty premises. The continued categorization by race in physiological research suggests that there are inherent differences between races, rather than addressing the specific underlying factors that result in health disparities between groups. The purpose of this Perspectives article is to provide a brief history of the genesis of categorization by race, why such categorization should be reconsidered in physiology research, and offer recommendations to more directly investigate the underlying factors that result in group disparities in cardiovascular and cerebrovascular health.

Four weeks of vitamin D supplementation improves nitric oxide-mediated microvascular function in college-aged African Americans.

Reduced nitric oxide (NO)-mediated cutaneous vasodilation, secondary to increased oxidative stress, presents in young African American (AA) compared with European American (EA) adults and may be modulated by vitamin D status. We assessed cutaneous microvascular function in 18 young, healthy (21 ± 2 yr; 9 men, 9 women) subjects before (pre, 8 AA, 10 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation and in 13 subjects after (post, 7 AA, 6 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation. Serum vitamin D concentrations [25(OH)D] were measured at each visit. Three intradermal microdialysis fibers placed in the ventral forearm were randomized for treatment with 10 µM Tempol, 100 µM apocynin, or lactated Ringer's solution (control). Local heating (39°C) induced cutaneous vasodilation; red cell flux was measured at each site (laser-Doppler flowmetry), and cutaneous vascular conductance (CVC = flux/MAP) was expressed as a percentage of maximum (28 mM sodium nitroprusside, +43°C) for each phase of local heating. After stable elevated blood flow was attained, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) was perfused at all sites to quantify the NO contribution to cutaneous vasodilation (%NO), calculated as the difference between local heating and l-NAME plateaus. Serum [25(OH)D], the magnitude of the local heating response, and %NO were all lower in AAs versus EAs (P < 0.01). Tempol (P = 0.01), but not apocynin (P ≥ 0.19), improved the local heating response and %NO. Four weeks of supplementation improved serum [25(OH)D], the local heating response, and %NO in AAs (P ≤ 0.04) but not in EAs (P ≥ 0.41). Vitamin D supplementation mitigated endothelial dysfunction, an antecedent to overt cardiovascular disease (CVD), in otherwise healthy, young AA adults.NEW & NOTEWORTHY Endothelial dysfunction, an antecedent to overt cardiovascular disease (CVD), is observed earlier and more frequently in otherwise healthy African Americans (AAs) when compared with other ethnic groups. Vitamin D may modulate endothelial function, and darkened skin pigmentation increases risk of vitamin D deficiency. We show that 4 wk of 2,000 IU/day vitamin D supplementation improves microvascular responses to local heating in AAs. Ensuring adequate vitamin D status may mitigate development of cardiovascular dysfunction in this at-risk population.

Healthy active older adults have enhanced K+ channel-dependent endothelial vasodilatory mechanisms.

Microvascular endothelial dysfunction, a precursor to atherosclerotic cardiovascular disease, increases with aging. Endothelium-derived hyperpolarizing factors (EDHFs), which act through K+ channels, regulate blood flow and are important to vascular health. It is unclear how EDHFs change with healthy aging. To evaluate microvascular endothelial reliance on K+ channel-mediated dilation as a function of age in healthy humans. Microvascular function was assessed using intradermal microdialysis in healthy younger (Y; n = 7; 3 M/4 W; 26 ± 1 yr) and older adults (O; n = 12; 5 M/7 W; 64 ± 2 yr) matched for V̇o2peak (Y: 39.0 ± 3.8, O: 37.6 ± 3.1 mL·kg-1·min-1). Participants underwent graded local infusions of: the K+ channel activator Na2S (10-6 to 10-1 M), acetylcholine (ACh, 10-10 to 10-1 M), ACh + the K+ channel inhibitor tetraethylammonium (TEA; 25 or 50 mM), and ACh + the nitric oxide synthase-inhibitor l-NAME (15 mM). Red blood cell flux was measured with laser-Doppler flowmetry and used to calculate cutaneous vascular conductance (CVC; flux/mean arterial pressure) as a percentage of each site-specific maximum (%CVCmax, 43°C+28 mM sodium nitroprusside). The %CVCmax response to Na2S was higher in older adults (mean, O: 51.7 ± 3.9% vs. Y: 36.1 ± 5.3%; P = 0.03). %CVCmax was lower in the ACh+TEA vs. the ACh site starting at 10-5 M (ACh: 34.0 ± 5.7% vs. ACh+TEA: 19.4 ± 4.5%; P = 0.002) in older and at 10-4 M (ACh: 54.5 ± 9.4% vs. ACh+TEA: 31.2 ± 6.7%; P = 0.0002) in younger adults. %CVCmax was lower in the ACh+l-NAME vs. the ACh site in both groups starting at 10-4 M ACh (Y: P < 0.001; O: P = 0.02). Healthy active older adults have enhanced K+ channel-dependent endothelial vasodilatory mechanisms, suggesting increased responsiveness to EDHFs with age.

Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide.

BACKGROUND: While excess dietary sodium impairs vascular function by increasing oxidative stress, the dietary incorporation of dairy foods improves vascular health. We demonstrated that single-meal cheese consumption ameliorates acute, sodium-induced endothelial dysfunction. However, controlled feeding studies examining the inclusion of cheese, a dairy product that contains both bioactive constituents and sodium, are lacking. OBJECTIVES: We tested the hypothesis that microcirculatory endothelium-dependent dilation (EDD) would be impaired by a high-sodium diet, but a sodium-matched diet high in dairy cheese would preserve EDD through oxidant stress mechanisms. METHODS: We gave 11 adults without salt-sensitive blood pressure (<10 mmHg Δ mean arterial pressure; 64 ± 2 y) 4 separate 8-d controlled dietary interventions in a randomized, crossover design: a low-sodium, no-dairy intervention (LNa; 1500 mg/d sodium); a low-sodium, high-cheese intervention (LNaC; 1500 mg/d sodium, 170 g/d cheese); a high-sodium, no-dairy intervention (HNa; 5500 mg/d sodium); and a high-sodium, high-cheese intervention (HNaC; 5500 mg/d sodium, 170 g/d cheese). On Day 8 of each diet, EDD was assessed through a localized infusion (intradermal microdialysis) of acetylcholine (ACh), both alone and during coinfusion of NG-nitro-L-arginine methyl ester (NO synthase inhibitor), L-ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibitor], or tempol (superoxide scavenger). RESULTS: Compared with LNa, microvascular responsiveness to ACh was attenuated during HNa (LNa: -4.82 ± 0.20 versus HNa: -3.21 ± 0.55 M logEC50; P = 0.03) but not LNaC (-5.44 ± 0.20 M logEC50) or HNaC (-4.46 ± 0.50 M logEC50). Further, ascorbate, apocynin, and tempol administration each increased ACh-induced vasodilation during HNa only (Ringer's: 38.9 ± 2.4; ascorbate: 48.0 ± 2.5; tempol: 45.3 ± 2.7; apocynin: 48.5 ± 2.6% maximum cutaneous vascular conductance; all P values < 0.01). CONCLUSIONS: These results demonstrate that incorporating dairy cheese into a high-sodium diet preserves EDD by decreasing the concentration of superoxide radicals. Consuming sodium in cheese, rather than in nondairy sources of sodium, may be an effective strategy to reduce cardiovascular disease risk in salt-insensitive, older adults. This trial was registered at clinicaltrials.gov as NCT03376555.

Cognitive performance in relation to hydration status and water intake among older adults, NHANES 2011-2014.

PURPOSE: Risks of dehydration and cognitive decline increase with advancing age, yet the relation between dehydration, water intake, and cognitive performance among older adults remains understudied. METHODS: Using data from the 2011-2014 cycles of the Nutrition and Health Examination Survey (NHANES), we tested if calculated serum osmolarity (Sosm) and adequate intake (AI) of water among women (n = 1271) and men (n = 1235) ≥ 60 years old were associated with scores of immediate and delayed recall, verbal fluency, and attention/processing speed. Sosm was categorized as < 285 (hyperhydrated), 285-289, 290-294, 295-300, or > 300 (dehydrated) mmol/L. AI of water was defined as ≥ 2 L/day for women and ≥ 2.5 L/day for men. RESULTS: Women with Sosm between 285 and 289 mmol/L scored 3.2-5.1 points higher on the Digit Symbol Substitution test (DSST) of attention/processing speed than women in other Sosm categories (P values < 0.05). There was evidence of a curvilinear relationship between DSST scores and Sosm among women and men (P values for quadratic terms < 0.02). Meeting an alternative AI on water intake of ≥ 1 mL/kcal and ≥ 1500 mL, but not the sex-specific AI, was associated with scoring one point higher on a verbal fluency test (P = 0.02) and two points higher on the DSST (P = 0.03) among women. Significant negative associations between dehydration or inadequate water intake and test scores were not observed among men. CONCLUSION: Hydration status and water intake were moderately associated with attention/processing speed among females. Future work should consider the effects of both dehydration and overhydration on cognitive function and investigate potential sex differences in cognitive responses to hydration status.

Historical reviews of the assessment of human cardiovascular function: interrogation and understanding of the control of skin blood flow.

Several techniques exist for the determination of skin blood flow that have historically been used in the investigation of thermoregulatory control of skin blood flow, and more recently, in clinical assessments or as an index of global vascular function. Skin blood flow measurement techniques differ in their methodology and their strengths and limitations. To examine the historical development of techniques for assessing skin blood flow by describing the origin, basic principles, and important aspects of each procedure and to provide recommendations for best practise. Venous occlusion plethysmography was one of the earliest techniques to intermittently index a limb's skin blood flow under conditions in which local muscle blood flow does not change. The introduction of laser Doppler flowmetry provided a method that continuously records an index of skin blood flow (red cell flux) (albeit from a relatively small skin area) that requires normalisation due to high site-to-site variability. The subsequent development of laser Doppler and laser speckle imaging techniques allows the mapping of skin blood flow from larger surface areas and the visualisation of capillary filling from the dermal plexus in two dimensions. The use of iontophoresis or intradermal microdialysis in conjunction with laser Doppler methods allows for the local delivery of pharmacological agents to interrogate the local and neural control of skin blood flow. The recent development of optical coherence tomography promises further advances in assessment of the skin circulation via three-dimensional imaging of the skin microvasculature for quantification of vessel diameter and vessel recruitment.

Ultraviolet Radiation Exposure, Risk, and Protection in Military and Outdoor Athletes.

Overexposure to ultraviolet radiation (UVR) from the sun is associated with deleterious health effects including, but not limited to, increased risk of skin cancers. Military personnel and those who participate in outdoor exercise or sports represent two potential populations at elevated risk of negative health consequences of UVR exposure due to large amounts of time spent outdoors, often in harsh UVR environments. Despite exposure to high and/or frequent doses of UVR in recreational and tactical athletes, adequate sun-protection practices are often disregarded or not well understood by many within these at-risk populations, resulting in heightened risk of negative UVR effects. The focus of this review is to examine the available literature regarding UVR exposure, risk of adverse health effects of UVR exposure, and sun protection practices in outdoor exercisers, athletes, and military personnel.

Chronic statin therapy is associated with enhanced cutaneous vascular responsiveness to sympathetic outflow during passive heat stress.

KEY POINTS: Impairments in both central sympathetic and peripheral microvascular function contribute to blunted reflex cutaneous vasodilatation during heat stress in healthy older adults. Hypercholesterolaemia is associated with decrements in neurovascular function; however, little is known about the impact of hypercholesterolaemia on the integrated responses to heat stress. Further, whether chronic statin therapy alters skin sympathetic outflow or its relation to cutaneous vascular conductance during heat stress is unknown. We demonstrate that reflex cutaneous vasodilatation is impaired in older hypercholesterolaemic adults but not in formerly hypercholesterolaemic adults currently treated with a statin compared to age-matched controls. Additionally, chronic statin treatment-induced improvements in reflex vasodilatation are mediated, in part, by increases in end-organ responsiveness to efferent sympathetic outflow during whole-body heating. These data add to the growing body of literature substantiating the beneficial pleiotropic neurovascular effects of chronic statin treatment and provide further support for the use of statins to confer additional cardioprotective benefits in older adults. ABSTRACT: Attenuated reflex cutaneous vasodilatation in healthy human ageing is mediated by alterations in both central (sympathetic outflow) and peripheral (microvascular endothelial) function. Hypercholesterolaemia is associated with further impairments in neurovascular function. HMG-CoA reductase inhibitors (statins) improve cutaneous endothelium-dependent dilatation; however, whether statin therapy alters skin sympathetic nervous system activity (SSNA) or its relation to cutaneous vascular conductance (CVC) during passive heat stress is unknown. We hypothesized that (1) hypercholesterolaemic older adults would demonstrate blunted increases in both SSNA and CVC during passive heating and (2) chronic statin treatment would improve the response range and sensitivity of the SSNA:CVC relation. Reflex vasodilatation in response to a 1.0°C rise in oral temperature (Tor ; water perfused suit) was induced in 13 healthy normocholesterolaemic adults (62 ± 2 years; LDL = 113 ± 7 mg/dl), 10 hypercholesterolaemic adults (60 ± 1 years; LDL = 183 ± 2 mg/dl), and 10 previously hypercholesterolaemic adults (64 ± 1 years; LDL = 102 ± 2 mg/dl) treated with lipophilic statin (10-40 mg daily). SSNA (peroneal microneurography) and red cell flux (laser-Doppler flowmetry) in the innervated dermatome (dorsum of foot) were continuously measured. Reflex vasodilatation was blunted in hypercholesterolaemic adults, but not in statin-treated adults, compared to normocholesterolaemic adults (at ∆Tor  = 1.0°C: normal = 36 ± 1%CVCmax , high = 32 ± 1%CVCmax , statin = 38 ± 1%CVCmax ; P < 0.01). ∆SSNA was not different (at ∆Tor  = 1.0°C: normal: ∆ = 393 ± 96%, high: ∆ = 311 ± 120%, statin: ∆ = 256 ± 90%; P = 0.11). The slope of the SSNA:CVC relation was blunted in hypercholesterolaemic adults (0.02 ± 0.03%CVCmax /%baseline ) compared to both normocholesterolaemic (0.09 ± 0.02%CVCmax /%baseline ; P = 0.024) and statin-treated (0.12 ± 0.05%CVCmax /%baseline ; P = 0.03) adults. Chronic statin treatment improves reflex cutaneous vasodilatation in formerly hypercholesterolaemic older adults by increasing end-organ responsiveness to sympathetic outflow during passive heat stress.