bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Role for Cyclooxygenase and Nitric Oxide Synthase in Sweating and Skin Blood Flow During Exercise in the Heat in Young Individuals with Type 1 Diabetes
Authors: Foudil‐bey Imane , Fujii Naoto , Dervis Sheila , Kenny Glen P. 
Published: November 2023

Recent studies show that individuals with type 1 diabetes mellitus (T1DM) have impaired heat loss responses. This is evidenced as a decrease in local sweat rate and an increase in core body temperature during exercise in the heat compared to non‐diabetic matches; however, the underlying mechanisms are currently unknown. Previous studies have shown that nitric oxide synthase (NOS) and cyclooxygenase (COX) increase sweating, while NOS, but not COX, contributes to cutaneous vasodilation in young adults exercising in the heat. Thus, the aim of our study was to determine if the impairments in local heat loss responses displayed by individuals with T1DM may be attributed to COX and/or NOS activity. Seven (5 males, 2 females) young (24±3 years) individuals with T1DM were instrumented with four microdialysis fibres in the forearm skin which were perfused with either 1) 10 mM ketorolac (KETO, non‐selective COX inhibitor), 2) 10 mM NG‐nitro‐L‐arginine methyl ester (L‐NAME, non‐selective NOS inhibitor), 3) a combination of L‐NAME and KETO (L‐NAME+KETO), or 4) lactated Ringer (Control). Sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC; laser Doppler perfusion units/mean arterial pressure) were measured continuously throughout the protocol. Participants performed two 30 min bouts of exercise at a fixed rate of heat production of 400 W in the heat (35°C, 20% relative humidity); separated by a 20‐ and 40‐min recovery respectively. During the first and second exercise bouts, we showed that the inhibition of COX (KETO) resulted in an increase in sweat rate relative to Control (average of last 5 min of second exercise; Control: 1.02±0.11 mg min−1 cm−2, KETO: 1.12±0.12 mg min−1 cm−2; P=0.029). However, a decrease in sweat rate was observed when both NOS and COX were inhibited (L‐NAME+KETO: 0.86±0.11 mg min−1 cm−2; P=0.031). Furthermore, inhibition of NOS alone did not significantly modulate sweating (L‐NAME: 0.93±0.11 mg min−1 cm−2; P=0.11). With respect to CVC, the inhibition of NOS (average of last 5 min of second exercise, 45±9%max), as well as NOS and COX (49±4%max) resulted in similar decreases in CVC relative to Control (68±1%max)(both P<0.05). In contrast, the inhibition of COX alone did not modulate CVC (64±4%max; P=0.33). Our results demonstrate that COX attenuates sweating during exercise in the heat in young adults with T1DM, which may occur through NOS‐dependent mechanisms. Finally, we show that individuals with T1DM exhibit NOS‐ but not COX‐dependent cutaneous vasodilation during exercise in the heat.Support or Funding InformationThis study was supported by grants from the Canadian Institutes of Health Research (286363; funds held by Dr. Glen P. Kenny).
Mitochondrial DNA damage is associated with earlier ventilatory threshold in military veterans with unexplained fatigue
Authors: Chen Yang , Jiao Xilu , Klein Jacquelyn , Ndirangu Duncan , Hill Helene Z , Condon Michael , Falvo Michael J 
Published: November 2023

Exercise intolerance and post‐exertion fatigueare common symptoms of individuals with mitochondrial dysfunction, and have recently been reported in veterans with unexplained fatigue. The goal of the present study was to assess direct (mtDNA damage) and indirect (cardiopulmonary exercise) measures of mitochondrial dysfunction in fatigued veterans. Twenty‐two(50.0±4.9 years) male veterans volunteered for this study. Each veteran completed general health questionnaire including following items: physical fatigue (44.7±13.8; Fatigue Severity Scale), physical activity questionnaire (1026.4±998.9 MET·min·wk−1), and smoking history (pack years 10.0±13.0). Each veteran provided peripheral blood mononuclear cells for total DNA extraction and mtDNA damage was determined by quantitative polymerase chain reaction. All veterans completed two consecutive maximal exercise tests separated by 24 hours. During each exercise bout, the time of ventilatory threshold (VT) was identified using the v‐slope method. The time of VT was identified as an effort‐independent measure of exercise performance reflective of mitochondrial capacity. MtDNA damage was correlated with physical activity (r=0.54, p= 0.004), time of VT at second b out exercise (r=−0.65, p= 0.001), but was not correlated with pack years, fatigue severity or time of VT at first bout exercise. Using partial correlation by controlling for physical activity and pack years, mtDNA damage was correlated to time of VT at second bout exercise (r=−0.64, p= 0.004). This is the first study to describe mitochondrial dysfunction through the relationship between mtDNA damage and an earlier onset of VT in veterans with unexplained fatigue. This may indicate that post‐exertion fatigue may be related to mitochondrial dysfunction. This work may guide new diagnostic testing and treatments for veterans suffering from with unexplained fatigue.Support or Funding InformationVA Grants 1I21RX001079‐01 and 1I21CX000797‐01 (Michael J Falvo).
Similar Effects between Follicular and Luteal Phases on the Urinary Levels of 6‐sulfatoxymelatonin following Endurance Exercise
Authors: Yasuda Nobuo , Tanioka Toshihiro 
Published: November 2023

The major urinary melatonin catabolite is 6‐sulfatoxymelatonin, which has been demonstrated as a good marker of pineal function. Although previous studies have shown exercise‐induced changes in melatonin metabolism, it still remains inconclusive whether prolonged exercise during two different menstrual cycle phases influences urinary 6‐sulfatoxymelatonin secretion. The purpose of the study was to determine the effects of the follicular and luteal phases on the urinary levels of 6‐sulfatoxymelatonin after 2‐h endurance exercise in women. Eleven recreationally active premenopausal women served as the participants (peak oxygen uptake (VO2peak): 46.1±5.0 mL/kg/min [mean±SD]). During the follicular (F: 5~8 days after the onset of the menses) and luteal (L: 22~25 days after the onset of the menses) phases, all participants carried out the same submaximal exercise protocol (2‐h cycling exercise at 60%VO2peak). Carbohydrate‐electrolyte solution was consumed every twenty minutes (2 ml/kg body mass) during each exercise protocol in order to delay fatigue and prevent hypoglycemia and dehydration. Before (Pre) and after (immediately Post) each exercise, spot urine samples were collected for later analysis of the urinary levels of 6‐sulfatoxymelatonin quantified by enzyme‐linked immunosorbent assay. Regarding the urinary levels of 6‐sulfatoxymelatonin (ng/mg creatinine), two‐way (phase × time) analysis of variances demonstrated a significant main effect for time (p<0.05), but not for phase or interaction (Pre=21.1±3.5, Post=33.0±8.5 for F; Pre=16.3±5.4, Post=33.5±9.5 for L). These findings indicate that acute moderate cycling exercise appears to be similar at the urinary levels of 6‐sulfatoxymelatonin during two different menstrual phases.Support or Funding InformationSupported partly by funds from the Grant‐in‐Aid for Scientific Research (C) (Grant No.23500867).
A More Efficient Method of Assessing Corner Store Healthfulness
Authors: DeWeese Robin , Todd Michael , Karpyn Allison , Yedidia Michael , Kennedy Michelle , Bruening Meg , Wharton Christopher , Ohri‐Vachaspati Punam 
Published: November 2023

IntroductionCompared to supermarkets, small/corner stores tend to stock lower proportions of healthy foods. Interventions targeting corner stores to increase healthy foods have been launched in many communities, and validated survey instruments have been developed to evaluate intervention effectiveness. However, in‐store evaluations can be infeasible and resource‐prohibitive due to time requirements. The purpose of this study was to develop a valid and feasible short form corner store audit tool (SCAT) that could be used in‐store or over the phone to capture the healthfulness of corner stores.MethodsAn adapted version of the Nutrition Environment Measures Survey for Corner Stores (NEMS‐CS) was used to conduct store audits of 229 corner stores in four New Jersey cities in 2014. Audit results were used in exploratory factor analysis and item response theory to develop the SCAT. In 2014 and 2015, a second round of audits was conducted in 96 corner stores to confirm the validity of the SCAT and to test its feasibility as a phone audit tool.ResultsThe SCAT was highly correlated with the adapted NEMS‐CS (r=0.79). SCAT scores placed stores in the same healthfulness categories as did the adapted NEMS‐CS in 88% of cases. Phone response matches indicated that store owners did not distinguish between 2% and low‐fat milk, and tended to round up the fruit and vegetable count to five if they had fewer varieties.ConclusionThe SCAT discriminates between higher versus lower healthfulness scores of corner stores and is feasible for use as a phone audit tool.Support or Funding InformationThis research was funded by a National Institute of Food and Agriculture predoctoral dissertation fellowship (20146701122279) and by a grant from the National Institute of Child Health and Human Development (1R01HD071583‐01A1)
A Novel Approach for Determining the Environmental Impacts of Individual Food Choices in the United States
Authors: Rose Diego , Heller Martin , Willits‐Smith Amelia , Mundorf Adrienne R. , Keoleian Gregory 
Published: November 2023

USDA and DHHS excluded sustainability as a topic for consideration in developing the 2015 Dietary Guidelines for Americans, contrary to recommendations by an expert advisory committee. While significant progress has been made in Europe and elsewhere in documenting the environmental impacts of different diets, very little work on this has been undertaken in the US, which might help explain their decision. To address this gap, we developed a novel approach to study the environmental impacts of individual food choices in the US. Individual 24‐hour recall data (N=28,276) from the National Health and Nutrition Examination Survey for 2005–2010 were converted to commodity form using resources from the US Environmental Protection Agency. There were 2.63 million food item/recipe components consumed by these individuals on the two days of recall, and these were converted to 461 different commodities. The environmental impacts of these food commodities – principally greenhouse gas emissions – were obtained from a comprehensive review of published life cycle assessment (LCA) studies. The LCA approach assesses inputs and outputs in the production, distribution, and consumption of products, and has seen increased application to foods in recent years. By matching the food choices of individuals to environmental impacts, we can quantify the impact of dietary choices on greenhouse gas emissions and other environmental impacts. Using aggregate agricultural food balance sheet data, we previously estimated mean greenhouse gas emissions from the U.S. diet to be 5.0 kg of carbon dioxide equivalents per person per day. The approach reported here will allow us to refine that estimate, and analyze the variation in the US population of this outcome by demographic and socio‐economic characteristics, as well as by diet knowledge and health behaviors. This cross‐disciplinary research demonstrates an approach that can inform future policy discussions regarding dietary recommendations and their potential impacts on sustainability.Support or Funding InformationThis work was supported by the Wellcome Trust (grant # 106854/Z/15/Z).
Blunted Increases in Skin Sympathetic Nerve Activity Contribute to the Attenuated Reflex Vasodilation in Aged Human Skin
Authors: Stanhewicz Anna E , Greaney Jody L , Alexander Lacy M , Kenney W. Larry 
Published: November 2023

When core and skin temperatures are elevated, reflex cutaneous vasodilation is attenuated in human aging, even in the absence of overt cardiovascular disease or elevated cardiovascular disease risk factors. This diminished response is mediated, in part, by age‐associated alterations in endothelial function; however the relative contribution of altered skin sympathetic nervous system activity (SSNA) remains unclear. We hypothesized that 1) apparently healthy older (O) adults would demonstrate blunted SSNA responses to increased core temperature compared to young (Y) adults, and 2) that the decreased SSNA response would be associated with an attenuated cutaneous vasodilation. Reflex vasodilation was induced in 8 Y (24 ± 1 yrs; range = 20–29 yrs) and 8 O (68 ± 2 yrs; range = 60–79 yrs) adults using a water‐perfused suit to elevate esophageal temperature (Tes) by 1.0°C. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome (the dorsum of foot) were continuously measured. SSNA was normalized to, and expressed as, a percentage of baseline. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure and expressed as a percentage of maximal CVC (local heating to 43°C). Reflex vasodilation was attenuated in O adults (O: 26±3 vs. Y: 56 ± 5 %CVCmax; p<0.001). During whole‐body heating, SSNA increased in both groups (p<0.05); however, the response was significantly blunted in O adults (O: Δ265 ± 79 vs. Y: Δ593 ± 73%; p=0.006). The increase in SSNA during heating was significantly correlated with cutaneous vasodilation in both Y (r2 = 0.97, p<0.001) and O (r2 = 0.92, p<0.001) adults throughout heating, with no age‐related differences in the slope of the linear regression between SSNA and %CVCmax (O: 0.06 ± 0.01 vs. Y: 0.07 ± 0.00; NS). These data demonstrate that age‐related impairments in reflex cutaneous vasodilation are mediated, in part, by a blunted efferent SSNA during hyperthermia.Support or Funding InformationACSM Research Endowment Grant
Thermotherapy Reduces Blood Pressure and Increases Leg Blood Flow in Patients With Symptomatic Peripheral Artery Disease
Authors: Roseguini Bruno Tesini , Neff Dustin , Kuhlenhoelter Alisha , Wong Brett , Motaganahalli Raghu 
Published: November 2023

Peripheral arterial disease (PAD) is characterized by atherosclerotic obstruction of the arteries in the lower extremities and affects approximately 10% of individuals older than 65 years. The most common clinical presentation of PAD is intermittent claudication (IC), defined as leg pain caused by insufficient blood flow during walking. Despite the increasing prevalence of this condition, few non‐invasive therapies exist to improve vascular function and exercise tolerance in patients with IC. Recent studies demonstrated that repeated exposure to thermotherapy (TT) alleviates the symptoms of the disease, but the mechanisms by which TT exerts its clinical benefits remain elusive. We tested the hypothesis that application of leg thermotherapy (TT) using a water‐circulating garment system would increase leg blood flow and reduce blood pressure in patients with IC. Fourteen patients (age: 63±9 yrs) completed two experimental sessions, at least 72 hrs apart, in a randomized, cross‐over design. In the TT session, water at 48°C was circulated through the garment for 90 min, while thermoneutral water (33°C) was used in the control intervention. Leg skin temperature, core body temperature, heart rate and blood pressure were measured before, during and for 2 hrs following the interventions. A subset of 7 patients also underwent a protocol for the measurement of blood flow in the popliteal artery before and during 90 min of TT using phase contrast magnetic resonance imaging. Application of TT for 90 min induced marked increases from baseline in leg skin temperature (from 32.9±0.3 to 39.8±0.5°C, p<0.01) and HR (from 64±3 to 76±4 bpm, p<0.01) as well as a modest increase in core temperature (from 36.9±0.1 to 37.5±0.2°C, p<0.01). Compared to the control intervention, TT promoted a sustained reduction in systolic (~14 mmHg) and diastolic (~6 mmHg) blood pressure (p<0.05). In addition, TT application induced a marked increase in peak blood flow velocity (~92%), average velocity (~81%), and average blood flow per min (~97%) in the popliteal artery (p<0.01). These findings indicate that TT is a simple and effective strategy to reduce blood pressure and enhance leg blood flow in patients with IC.Support or Funding InformationIndiana Clinical and Translational Science Institute Project Development Team
Daily Adaptive Changes in Blood Chemistry of Pigs Exposed to Heat Stress
Authors: Trejo Adriana Morales , Ibarra Nely , Castillo Gilberto , Pérez Misael , Castro Pedro , Avelar Ernesto , Cervantes Miguel 
Published: November 2023

Animals and humans exposed to heat stress (HS) conditions may modify their physiology and metabolism to maintain homeostasis. In the dessert regions of the world, they have to adapt to great changes in ambient temperature (AT) within 24‐h periods, from thermo neutral (TN) AT early in the morning to stressful high AT in the afternoon. An experiment was conducted with six pigs (45 kg BW), individually housed, during the summer of Northwestern Mexico to analyze the impact of HS as well as the diurnal changes in AT on their blood chemistry. First, the pigs were housed under natural HS conditions (30.4 – 41.1° C, HS) during 14 d. Then, the pigs were moved to an air‐conditioned room (22.6–25.1 °C, TN) for two weeks. Blood samples were collected from the jugular vein of pigs at 0600, 1200 and 1600 h, during the last three days under HS, and again on the last day under TN conditions. Samples were processed to obtain serum in which blood chemistry parameters were analyzed. Heat stress reduced the serum concentration of cholesterol, total proteins, albumin, globulin, phosphorus, and Ala‐amino‐transferase (P<0.05); indirect bilirubin tended to reduce (P<0.10), and calcium tended to increase (P<0.10). As for the diurnal changes in AT, Ca SC decreased at 1200 and 1600 h (P<0.001) as compared with that at 0600; cholesterol also reduced at 1600 h compared to 0600 h (P<0.05). These changes indicate that HS animals modify their physiology and that some factors such as blood proteins, cholesterol and calcium are modified along the day in order to maintain pig homeostasis.Support or Funding InformationCONACYT, México. Ciencia básica 2012, 00181348.
Menstrual Cycle Phase does not Influence Whole Body Heat Loss Responses During Exercise in the Heat
Authors: Dervis Sheila , Poirier Martin P. , Paull Gabrielle , Zhang Sarah Y. , Kenny Glen P. 
Published: November 2023

Traditionally, female reproductive hormones (i.e., estrogen and progesterone) have been shown to independently influence local thermal responses during exercise in the heat. Consequently, studies examining thermal responses during exercise usually only test females during the early follicular phase of the menstrual cycle (i.e., first five days) when estrogen and progesterone are at their lowest levels. However, it remains unclear whether local thermal responses translate into comparable changes in whole‐body heat loss throughout the menstrual cycle. Therefore, we examined changes in whole‐body evaporative heat loss as determined using direct calorimetry in the early follicular (i.e., when both estrogen and progesterone levels are low), late follicular (i.e., when estrogen levels are high) and mid‐luteal (i.e., when both progesterone and estrogen levels are high) phases in young females (n=5, 21±2 years). Participants performed three 30‐min bouts of semi‐recumbent cycling at a fixed rate of metabolic heat production equal to 250 (Ex1), 325 (Ex2) and 415 W (Ex3) in the heat (40°C and 15% relative humidity), each bout followed by 15‐min of recovery. Whole‐body heat loss (evaporative and dry) and metabolic heat production were measured by direct and indirect calorimetry, respectively. Whole‐body heat content was calculated as the temporal summation of heat production and heat loss. Our preliminary results demonstrate that the combined rate of metabolic heat production and dry heat gain (i.e., net heat load) was similar between hormonal phases throughout the incremental intermittent exercise protocol (P>0.05). The rate of whole‐body evaporative heat loss measured during the early follicular (Ex1: 259±10 W, Ex2: 328±17 W, Ex3: 353±20 W), late follicular (Ex1: 248±27 W, Ex2: 306±36 W, Ex3: 337±31 W) and mid‐luteal phases (Ex1: 246±21 W, Ex2: 304±52 W, Ex3: 346±46 W) of the menstrual cycle were similar between phases for each exercise bout (P≥0.05). Accordingly, whole‐body heat content was also similar (early follicular: Ex1: 124±80 kJ, Ex2: 147±80 kJ, Ex3: 247±78 kJ; late follicular: Ex1: 125±27 kJ, Ex2: 139±17 kJ, Ex3: 180±59 kJ; mid‐luteal: Ex1: 121±28 kJ, Ex2: 147±39 kJ, Ex3: 213±49 kJ) (P>0.05). Our preliminary findings suggest that ovarian hormone fluctuations (i.e., estrogen and progesterone) during the menstrual cycle in young females do not influence whole‐body heat dissipation and therefore the amount of heat stored during exercise in the heat.Support or Funding InformationFunding support: This study was supported by grants from the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014; funds held by Dr. Glen P. Kenny).
The Effect of ETA and ETB Receptor Inhibition on Cutaneous Vasodilation and Sweating in Young Males During Rest and Exercise in the Heat
Authors: Singh Maya , Halili Lyra , Fujii Naoto , Kenny Glen P 
Published: November 2023

During heat stress, increases in cutaneous blood flow and sweating are the main avenues by which a stable core body temperature can be maintained. However, the mechanisms underlying these responses remain elusive. Endothelin‐1 (ET‐1) is a powerful vasoconstrictor that can activate both endothelin A (ETA) and endothelin B (ETB) receptor subtypes, which contribute to the cutaneous vasodilation response induced by local skin heating. Additionally, both receptors are found on the human eccrine sweat glands. Given that ETA receptor activation can reduce nitric oxide (NO) bioavailability, which is known to augment both cutaneous vasodilation and sweating, we evaluated the hypothesis that the activation of ETA receptors may attenuate cutaneous vasodilation and sweating during heat stress. In this study, eight males (25 ± 4 years) performed an intermittent cycling protocol on a semi‐recumbent bicycle consisting of two 30 min bouts of moderate (40% VO2max) and high (75% VO2max) intensity exercise in the heat (35°C); separated by a 20‐ and 40‐ min recovery period respectively. Cutaneous vascular conductance (CVC, laser‐Doppler perfusion units/mean arterial pressure), normalized to maximal CVC, and sweat rate (ventilated capsule) were evaluated at four intradermal microdialysis forearm skin sites. Each site was perfused with either 1) lactated Ringer (Control), 2) 500 nM BQ‐123 (a selective ETA receptor blocker), 3) 300 nM BQ‐788 (a selective ETB receptor blocker), or 4) a combination of BQ‐123 and BQ‐788. During both exercise bouts, relative to Control (Exercise 1: 47 ± 8%max; Exercise 2: 62 ± 1%max), there were no between‐site differences in CVC (all P > 0.05). However, at the end of each recovery period, the blockade of ETA receptors (Recovery 1: 49 ± 4%max; Recovery 2: 49 ± 3%max) and the dual blockade of ETA and ETB receptors (Recovery 1: 49 ± 7%max; Recovery 2: 57 ± 8%max) augmented CVC in comparison to Control (Recovery 1: 33 ± 6%max; Recovery 2: 39 ± 5%max; P < 0.05). We observed no between‐site differences in sweat rate throughout the protocol from baseline rest to the end of the second recovery (all P > 0.05). We show that neither ETA nor ETB receptors modulate cutaneous perfusion and sweating during exercise in the heat. Furthermore, we demonstrate that activation of ETA receptors reduces cutaneous perfusion during passive heat stress after exercise in the heat.Support or Funding InformationThis study was supported by grants from the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014; funds held by Dr. Glen P. Kenny).