Plasma epinephrine and norepinephrine responses to extreme heat exposures in young and older adults.

Hyperthermia is known as a hyperadrenergic state, yet there is a lack of data on the sympathetic responses to ambient heat stress in humans. Therefore, we investigated the plasma epinephrine and norepinephrine concentrations of healthy young and older adults exposed to 3 h of very hot and dry, as well as hot and humid, heat, both with accompanying activities of daily living. We hypothesized that older adults, compared with young adults, would have augmented increases in epinephrine and norepinephrine concentrations secondary to increased thermal strain. Young (n = 20) and older (n = 18) participants underwent two 3-h heat exposures on different days: very hot and dry [47°C and 15% relative humidity (RH)] and hot and humid (41°C and 40% RH). To mimic heat generation comparable to activities of daily living, participants performed seven 5-min bouts of light cycling (approximately 3 METS) dispersed throughout the heat exposure. We measured plasma concentrations of epinephrine and norepinephrine at baseline, end, and 2-h postheat exposure. There was a group-wide increase in epinephrine from baseline to the end of the heat exposure (Δ19 ± 27 pg/mL; P < 0.001) in the hot and humid condition, but not in the very hot and dry condition (Δ6 ± 19 pg/mL; P = 0.10). There were group-wide decreases in norepinephrine concentrations from baseline to the end of the heat exposure in both the very hot and dry (Δ-131 ± 169 pg/mL; P < 0.001) and the hot and humid (Δ-138 ± 157 pg/mL; P < 0.001) conditions, with both returning to near baseline at 2-h postexposure. These data suggest that ambient heating with accompanying bouts of light intermittent exercise may lead to decreases in circulating concentrations of norepinephrine.NEW & NOTEWORTHY Herein we present plasma epinephrine and norepinephrine concentrations to 3 h of very hot and dry, as well as hot and humid, heat exposures with accompanying activities of daily living in young and older participants. We found 1) increased plasma concentrations of epinephrine in young and older adults following the hot and humid, but not the very hot and dry exposures and 2) decreased concentrations of norepinephrine in both groups following exposure to both conditions.

Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during the cold pressor test.

Hemorrhage is a leading cause of death in the pre-hospital setting. Since pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unique hypotheses: a) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia, and b) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. Following sublingual administration of sufentanil (30 µg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance, followed by a cold pressor test (CPT) after LBNP recovery. Addressing the first aim, tolerance to LBNP was not different between trials (p = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time: p<0.001, trial p=0.477, interaction p=0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time: p < 0.001, trial p= p=0.626, interaction p = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (p < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (p = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.

Whole-body cooling effectiveness of cold intravenous saline following exercise hyperthermia: a randomized trial.

INTRODUCTION: In some athletic, occupational, military and emergency settings, cold intravenous (IV) fluids are used to facilitate whole-body cooling in an effort to treat heat illness. This treatment has anecdotal support, but currently lacks evidence supporting it as a whole-body cooling modality. Other modalities may offer superior cooling rates, and thus, patient outcomes following treatment. We sought to evaluate cooling rates of cold-IV normal saline immediately following exercise-induced hyperthermia. METHODS: Eight healthy participants (3 females; 25 ± 2y; 72.9 ± 10.9 kg) completed 2 trials in random order. Prior to exercise, participants provided a small urine sample to confirm hydration status via urine specific gravity. Wet bulb globe temperature (WBGT) was assessed throughout trials. In both trials, participants exercised outdoors until rectal temperature (Tre) reached ∼38.9 °C, or volitional exhaustion, and then were cooled. In cooling, participants received either cold-IV (∼5 °C 0.9% NaCl fluids) or no treatment (sat in the shade; passive). Throughout exercise and treatment, Tre and heart rate (HR) were monitored. During exercise and every 10 min throughout cooling, participants were asked to assess thermal sensation. RESULTS: Hydration status (P = .847) was not significantly different prior to exercise between trials. WBGT throughout was not different between trials (P = .426). Maximum Tre reached was not different between cold-IV (38.88 ± 0.30 °C) and passive cooling (38.76 ± 0.28 °C) trials (P = .184). Mean cooling rate for cold-IV (0.039 ± 0.005 °C·min-1) was significantly greater than for passive cooling (0.028 ± 0.005 °C·min-1; P = .002). Tre throughout cooling was not different between trials (P = .707), but did decrease throughout (P = .008), regardless of trial. HR was decreased over time (P < .001), but cold-IV and passive cooling were not different throughout HR recovery (P = .141). Thermal sensation decreased throughout cooling (P < .001), but was not different between trials (p = .278). CONCLUSION: Emergency medical personnel should adopt treatment protocols that employ documented effective treatments for exertional heat stroke. In isolation, our data casts significant doubt for the use of cold-IV saline infusion for whole-body cooling of hyperthermic individuals.

Kidney Function Biomarkers During Extreme Heat Exposure in Young and Older Adults.

This study investigates the effects of extreme heat exposure on kidney function using plasma-based biomarkers in young and older adults.

SAAMP 2.0: An algorithm to predict genotype-phenotype correlation of lysosomal storage diseases.

Lysosomal storage diseases (LSDs) are a group of genetic disorders, resulting from deficiencies of lysosomal enzyme. Genotype-phenotype correlation is essential for timely and proper treatment allocation. Recently, by integrating prediction outcomes of 7 bioinformatics tools, we developed a SAAMP algorithm to predict the impact of individual amino-acid substitution. To optimize this approach, we evaluated the performance of these bioinformatics tools in a broad array of genes. PolyPhen and PROVEAN had the best performances, while SNP&GOs, PANTHER and I-Mutant had the worst performances. Therefore, SAAMP 2.0 was developed by excluding 3 tools with worst performance, yielding a sensitivity of 94% and a specificity of 90%. To generalize the guideline to proteins without known structures, we built the three-dimensional model of iduronate-2-sulfatase by homology modeling. Further, we investigated the phenotype severity of known disease-causing mutations of the GLB1 gene, which lead to 2 LSDs (GM1 gangliosidosis and Morquio disease type B). Based on the previous literature and structural analysis, we associated these mutations with disease subtypes and proposed a theory to explain the complicated genotype-phenotype correlation. Collectively, an updated guideline for phenotype prediction with SAAMP 2.0 was proposed, which will provide essential information for early diagnosis and proper treatment allocation, and they may be generalized to many monogenic diseases.

Sports drinks do not increase acute kidney injury risk in males during industrial work in the heat when euhydration is maintained, a randomized crossover trial.

Industrial workers regularly perform physical labor under high heat stress, which may place them at risk for dehydration and acute kidney injury. Current guidelines recommend that workers should consume sports drinks to maintain euhydration during work shifts. However, the impact of fructose sweetened sports drinks on acute kidney injury risk is unknown. The purpose of this study was to investigate the effects of sports drink consumption on markers of acute kidney injury following simulated industrial work in the heat. Twenty males completed two matched 2 h simulated industrial work trial visits in a warm and humid environment (30 °C and 55% relative humidity). During and following the bout of simulated work, participants consumed either a commercially available sports drink or a noncaloric placebo. Urine and blood samples, collected pre-, post-, and 16 h post-work were assayed for markers of hydration (plasma/urine osmolality, and urine specific gravity) and acute kidney injury (KIM-1 and NGAL). There were no differences in physiological or perceptual responses to the bout of work (interaction p > 0.05 for all indices), and markers of hydration were similar between trials (interaction p > 0.05 for all indices). KIM-1 (Placebo: Δ Ln 1.18 ± 1.64; Sports drink: Δ Ln 1.49 ± 1.10 pg/mL; groupwide d = 0.89, p < 0.001) and NGAL (Placebo: Δ Ln 0.44 ± 1.11; Sports drink: Δ Ln 0.67 ± 1.22 pg/mL; groupwide d = 0.39, p = 0.03) were elevated pre- to post-work, but there were no differences between trials (interaction p > 0.05). These data provide no evidence that consumption of fructose sweetened sports drinks increases the risk of acute kidney injury during physical work in the heat.

Compensatory reserve index during central hypovolemia and volume loading in healthy young and older hyperthermic adults: A pilot study.

The compensatory reserve index (CRI), derived from machine learning algorithms from peripherally obtained photoplethysmography signals, provides a non-invasive assessment of cardiovascular stability, that may be useful clinically. Briefly, the CRI device provides a value between 0 and 1, with 1 reflecting full compensable capabilities and 0 reflecting little to no compensable capabilities. However, the CRI algorithm was developed in younger to middle aged adults, such that it is unknown if older age modulates CRI responses to cardiovascular challenges. In young and older subjects, we compared CRI responses to normothermic and hyperthermic progressive lower body negative pressure (LBNP), and volume loading with saline infusion. Eleven younger (20-36 years) and 10 older (61-75 years) healthy participants underwent (1) graded normothermic LBNP up to 30 mmHg, (2) graded hyperthermic (1.5°C increase in blood temperature) LBNP up to 30 mmHg, and (3) infusion of 15 mL/kg saline (volume loading) with hyperthermia maintained. CRI was obtained throughout each procedure. CRI at 30 mmHg LBNP was 0.18 and 0.24 units greater in the older group during normothermic and hyperthermic LBNP, respectively. However, CRI was not different between age groups at any other LBNP stage, nor did CRI change with volume loading regardless of age. In response to passive hyperthermia alone, regression analyses showed that heart rate was the strongest predictor of CRI. Blood temperature, rate pressure product, and stroke volume were also predictive of CRI but to a lesser extent. In conclusion, age attenuates the reduction in CRI during progressive normothermic and hyperthermic LBNP, but only at 30 mmHg. Second, the CRI was unchanged during volume loading in all subjects. Future studies should determine whether the age differences in CRI reflect age differences in LBNP tolerance.

Sex Differences in Sympathetic Responses to Lower-Body Negative Pressure.

INTRODUCTION: Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. METHODS: Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). RESULTS: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex). CONCLUSIONS: Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.

Aging Increases Enterocyte Damage during a 3-Hour Exposure to Very Hot and Dry Heat: A Preliminary Study.

Profound heat stress can damage the gastrointestinal barrier, leading to microbial translocation from the gut and subsequent systemic inflammation. Despite the greater vulnerability of older people to heat wave-related morbidity and mortality, it is unknown if age modulates gastrointestinal barrier damage and inflammation during heat stress. Therefore, the aim of this study was to determine if aging impacted enterocyte damage and systemic inflammatory responses to a 3-h exposure to very hot and dry (47 °C, 15% humidity) heat with accompanying activities of daily living (intermittent activity at 3 METS). Data from 16 young (age 21 to 39 years) and 16 older (age 65 to 76 years) humans were used to address this aim. In each group, log-transformed plasma concentrations of intestinal fatty acid binding protein (I-FABPlog), interleukin-8 (IL-8log), and tissue factor (TFlog) were assessed as indices of enterocyte damage, systemic inflammation, and blood coagulation, respectively, before and after the 3-h heat exposure. In the younger cohort, I-FABPlog concentration did not increase from pre to post heat exposure (p = 0.264, d = 0.20), although it was elevated in the older group (p = 0.014, d = 0.67). The magnitude of the increase in I-FABPlog was greater in the older participants (p = 0.084, d = 0.55). Across all participants, there was no correlation between the change in core temperature and the change in IFABPlog. There was no change in IL-8log in the younger group (p = 0.193, d = 0.23) following heat exposure, but we observed a decrease in IL-8log in the older group (p = 0.047, d = 0.48). TFlog decreased in the younger group (p = 0.071, d = 0.41), but did not change in the older group (p = 0.193, d = 0.15). Our data indicate that I-FABPlog concentration (an index of enterocyte damage) is increased in older humans during a 3-h extreme heat exposure. Future studies should determine whether this marker reflects increased gastrointestinal barrier permeability in older individuals during heat exposure.

Gastrointestinal cell injury and perceived symptoms after running the Boston Marathon.

Gastrointestinal (GI) disturbances are a prevalent cause of marathon related complaints, and in extreme cases can promote life-threatening conditions such as exertional heat stroke. Our aim was to study intestinal cell injury [via intestinal fatty acid binding protein (I-FABP)] and perceived GI distress symptoms among marathon runners. We also examined potential risk factors (e.g., inadequate sleep) that could exacerbate GI disturbances in healthy, trained endurance runners. This was a parallel mixed-methods study design. 2019 Boston Marathon participants were recruited via email and subjects completed surveys before the race describing demographics and training history. Participants completed a GI questionnaire to assess presence and severity of symptoms, a survey regarding risk factors (e.g., recent illness, medications) that could promote GI disturbances, and provided a urine sample at three time points (immediately pre-race, post-race, and 24-h post-race). Due to weather, blood samples were only collected immediately and 24-h post-race. A total of 40 runners (males: n = 19, age = 44.9 ± 10.8 years; females: n = 21, age = 44.8 ± 10.6 years) completed this study. I-FABP significantly decreased from post-race (3367.5 ± 2633.5 pg/mL) to 24-h post-race (1657.3 ± 950.7 pg/mL, t (39) = -4.228, p < .001, d = -.669). There was a significant difference in overall GI symptom scores across the three time points (F (2, 39) = 41.37, p < .001). The highest average score occurred post-race (.84 ± .68), compared to pre-race (.09 ± .12) and 24-h post-race (.44 ± .28). Post-race I-FABP (r = .31, p = .048) and post-race urine specific gravity (r = .33, p = .041) were significantly correlated with post-race GI symptom scores. Our study provides further support to the individualized nature of GI disturbances, with participants experiencing a wide range of risk factors that can influence the extent of GI damage and perceived symptoms during and after exercise.

Age alters the thermoregulatory responses to extreme heat exposure with accompanying activities of daily living.

Older adults are at greater risk for heat-related morbidity and mortality, due in part to age-related reductions in heat dissipating capabilities. Previous studies investigating the impact of age on responses to heat stress used approaches that lack activities of daily living and therefore may not accurately depict the thermal/physiological strain that would occur during actual heatwaves. We sought to compare the responses of young (18-39 yr) and older (≥65 yr) adults exposed to two extreme heat simulations. Healthy young (n = 20) and older (n = 20) participants underwent two 3-h extreme heat exposures on different days: 1) DRY (47°C and 15% humidity) and 2) HUMID (41°C and 40% humidity). To mimic heat generation comparable with activities of daily living, participants performed 5-min bouts of light physical activity dispersed throughout the heat exposure. Measurements included core and skin temperatures, heart rate, blood pressure, local and whole body sweat rate, forearm blood flow, and perceptual responses. Δ core temperature (Young: 0.68 ± 0.27°C vs. Older: 1.37 ± 0.42°C; P < 0.001) and ending core temperature (Young: 37.81 ± 0.26°C vs. Older: 38.15 ± 0.43°C; P = 0.005) were greater in the older cohort during the DRY condition. Δ core temperature (Young: 0.58 ± 0.25°C vs. Older: 1.02 ± 0.32°C; P < 0.001), but not ending core temperature (Young: 37.67 ± 0.34°C vs. Older: 37.83 ± 0.35°C; P = 0.151), was higher in the older cohort during the HUMID condition. We demonstrated that older adults have diminished thermoregulatory responses to heat stress with accompanying activities of daily living. These findings corroborate previous reports and confirm epidemiological data showing that older adults are at a greater risk for hyperthermia.NEW & NOTEWORTHY Using an experimental model of extreme heat exposure that incorporates brief periods of light physical activity to simulate activities of daily living, the extent of thermal strain reported herein more accurately represents what would occur during actual heatwave conditions. Despite matching metabolic heat generation and environmental conditions, we show that older adults have augmented core temperature responses, likely due to age-related reductions in heat dissipating mechanisms.

Attrition of Well-Healed Burn Survivors to a 6-Month Community-Based Exercise Program: A Retrospective Evaluation.

The purpose of this study was to evaluate whether burn survivors have lower adherence compared to non-burned control individuals during a 6-month community-based exercise program. In burn survivors, we sought to answer if there was a relation between the size of the burn injury and dropout frequency. Fifty-two burn survivors and 15 non-burned controls (n = 67) were recruited for a 6-month community-based (ie, non-supervised), progressive, exercise training program. During the exercise program, 27% (ie, 4 of the 15 enrolled) of the non-burned individuals dropped out of the study, while 37% (ie, 19 of the 52) of the burn survivors dropped out from the study. There was no difference in the percentage of individuals who dropped out between groups (P = .552). There was no difference in size of the burn injury, expressed as percent body surface area burned (%BSA) between the burn survivors that dropped out versus those who completed the exercise regimen (P = .951). We did not observe a relation between %BSA burned and dropouts (log odds = -0.15-0.01(%BSA), B = -0.01, SE = 0.015, P = .541). There was no effect of %BSA burned on the probability of dropout [Exp (B) = 0.991, 95% CI (0.961, 1.020)] and there were no differences in the percentage of individuals who dropped out of the study based on %BSA burned (χ2(1) = 0.44, P = .51). These data demonstrate that burn survivors have similar exercise adherence relative to a non-burned group and the extent of a burn injury does not affect exercise program adherence.

Cardiac remodeling in well-healed burn survivors after 6 months of unsupervised progressive exercise training.

Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training improves cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Secondary analyses explored relations between burn surface area and changes in cardiac structure in the cohort of burn survivors. V̇o2peak assessments and cardiac magnetic resonance imaging were performed at baseline and following 6 months of progressive exercise training from 19 well-healed burn survivors and 10 nonburned control participants. V̇o2peak increased following 6 months of training in both groups (Control: Δ5.5 ± 5.8 mL/kg/min; Burn Survivors: Δ3.2 ± 3.6 mL/kg/min, main effect of training, P < 0.001). Left ventricle (LV) mass (Control: Δ1.7 ± 3.1 g/m2; Burn survivors: Δ1.8 ± 2.7 g/m2), stroke volume (Control: Δ5.8 ± 5.2 mL/m2; Burn Survivors: Δ2.8 ± 4.2 mL/m2), and ejection fraction (Control: Δ2.4 ± 4.0%; Burn Survivors: Δ2.2 ± 4.3%) similarly increased following 6 months of exercise training in both cohorts (main effect of training P < 0.05 for all indexes). LV end-diastolic volume increased in the control group (Δ6.5 ± 4.5 mL/m2) but not in the cohort of burn survivors (Δ1.9 ± 2.7 mL/m2, interaction, P = 0.040). Multiple linear regression analyses revealed that burn surface area had little to no effect on changes in ventricular mass or end-diastolic volumes in response to exercise training. Our findings provide initial evidence of physiological cardiac remodeling, which is not impacted by burn size, in response to exercise training in individuals with well-healed burn injuries.NEW & NOTEWORTHY Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training would improve cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Our findings highlight the ability of exercise training to modify cardiac structure and function in well-healed burn survivors and nonburned sedentary controls alike.

Response to a Water Bolus in Long Term Oral Contraceptive Users.

The purpose of our study was to determine the responses to an acute water bolus in long-term oral contraception (OCP) users. Seventeen female volunteers (27 ± 5 y, 64.1 ± 13.7 kg, 39.6 ± 5.9 kg/LBM) provided consent and enrolled in our study. All were long-term OCP users and participated in two trials, one during the active pill (High Hormone, HH) dose of their prescribed OCP and one during the sham pill (Low Hormone, LH) dose. Participants reported to the laboratory euhydrated, were fed breakfast, remained seated for 60 min and were provided a bolus of room temperature water in the amount of 12 mL/kg/LBM. Urine output over 180 min was measured. Nude body mass was measured pre- and post-trial. Urine specific gravity (USG) and urine osmolality were analyzed. Between trials, there were no differences in 3-h total urine volume (P = 0.296), 3-h USG (P = 0.225), 3-h urine osmolality (P = 0.088), or 3-h urine frequency (P = 0.367). Heart rate was not different between trials (P = 0.792) nor over time (P = 0.731). Mean arterial pressure was not different between trials (P = 0.099) nor over time (P = 0.262). Perceived thirst demonstrated a significant main effect for increasing over time regardless of trial (P < 0.001) but there was no difference between trials (P = 0.731). The urgency to void was not different between trials (P = 0.149) nor over time (P = 0.615). Plasma volume change was not different between trials (P = 0.847) (HH: -3.4 ± 5.0, LH post: -3.8 ± 4.5%) and plasma osmolality did not differ between trials (P = 0.290) nor over time (P = 0.967) (HH pre: 290 ± 4, HH post: 289 ± 4, LH pre: 291 ± 4, LH post: 291 ± 4 mosm/L). Blood glucose significantly decreased over time (P < 0.001) but there was no difference between trials (P = 0.780) (HH pre: 95.9 ± 113.9, HH post: 86.8 ± 6.5, LH pre: 95.9 ± 13.5, LH post: 84.6 ± 9.4 mmol/L). Copeptin concentration did not differ between phases of OCP use (P = 0.645) nor from pre- to post-trial (P = 0.787) Despite fluctuations in hormone concentrations, responses to a water bolus seem to be unaffected in OCP users in euhydrated, resting conditions.

Men's lacrosse protective equipment increases strain during exercise in the heat.

OBJECTIVES: The purpose of this study was to determine thermoregulatory and cardiovascular effects of wearing men's lacrosse protective equipment during simulated lacrosse activities in the heat. DESIGN: We conducted a randomized, controlled, crossover study. METHODS: Thirteen healthy men (22 ±â€¯3 y, 76.2 ±â€¯8.9 kg, 181 ±â€¯6 cm, 16.06 ±â€¯6.16% body fat) completed two matched exercise trials in the heat (WBGT: 25.5 ±â€¯0.8 °C). In randomized order, participants donned full men's lacrosse equipment (helmet, shoulder/elbow pads, and gloves) in one trial while the other included no equipment. Participants completed a topography body scan to determine specific body surface area covered with equipment. Rectal temperature (Tre), heart rate (HR), and mean weighted skin temperature (Tsk) were measured throughout trials. Whole body sweat rate was assessed for trial comparisons. RESULTS: The equipment covered 32.62 ±â€¯2.53% body surface area in our participants. Post-exercise Tre was significantly greater with equipment (39.36 ±â€¯0.04 °C) compared to control (38.98 ±â€¯0.49 °C; p = .007). The overall rate of rise of Tre was significantly greater with equipment (0.043 ±â€¯0.015 °C·min-1) compared to control (0.031 ±â€¯0.008 °Cmin-1; p = .041). Regardless of time point, HR and Tsk were significantly elevated with equipment compared to control trial (p ≤ .026). Sweat rates were elevated with equipment (1.76 ±â€¯0.74 L·h-1) compared to shorts and t-shirt (1.13 ±â€¯0.26 L·h-1), but this difference was not significant (p = .058). CONCLUSIONS: Our data indicate impairments in heat dissipation and increased cardiovascular strain imposed by men's lacrosse equipment.

Acute Kidney Injury Biomarkers and Hydration Outcomes at the Boston Marathon.

The purpose of our field study was to investigate the effects of running the Boston Marathon on acute kidney injury (AKI) biomarkers. We hypothesized that biomarker values would be elevated immediately post-marathon but would resolve in the 24-h post-marathon. Secondarily, we sought to identify sex differences related to renal stress. Participants were 65 runners who completed the Boston Marathon (46 ± 9 years, 65.4 ± 10.8 kg). Urine samples were collected at three different time points (pre-marathon, post-marathon, and 24-h post-marathon). Blood samples were collected post-marathon and 24-h post-marathon. Urine specific gravity (USG) and AKI biomarkers were evaluated. Pre-marathon USG (1.012 ± 0.007) was significantly less than post-marathon (1.018 ± 0.008) and 24-h post-marathon (1.020 ± 0.009; P < 0.001). Male USG (1.024 ± 0.009) was significantly greater 24-h post-marathon than females (1.017 ± 0.008; P = 0.019). Urinary neutrophil gelatinase-associated lipocalin values were significantly greater over time (P < 0.001), and there was a main effect of sex with female urinary creatinine (UCr) greater than males at all three time points (P = 0.040). Post-marathonUCr (366.24 ± 295.16 mg/dl) was significantly greater than pre-marathon (206.65 ± 145.28.56 mg/dl; p < 0.001) and 24-h post-marathon was significantly lower than other time-points (93.90 ± 125.07 mg/dl; P < 0.001). FemaleUCr values were significantly greater than males 24-h post-marathon (P < 0.001). There was no difference in serum cystatin C (SCys) values post- or 24-h post-marathon (P = 0.178). Serum creatinine (SCr) significantly decreased between post-marathon and 24-h post-marathon, (P < 0.001). We can infer that the characteristics unique to the Boston Marathon may have attributed to prolonged elevations in AKI biomarkers. Sex differences were observed during the Boston Marathon warranting further investigation.

The nature and impact of neurobehavioral symptoms in neuronopathic Hunter syndrome.

In neuronopathic Hunter syndrome, neurobehavioral symptoms are known to be serious but have been incompletely described. While families face significant stress stemming from this complex and far-reaching array of symptoms, neither caregiver burden nor the neurobehavioral symptoms have been measured comprehensively. We delineated these neurobehavioral characteristics and their impact on the caregiver using multiple approaches. Methods: As part of the initial phase of developing a Hunter-specific behavioral assessment tool, we used multiple methods to obtain data on patient behaviors and caregiver burden, with the intention of drafting item sets for the tool. We utilized 1) caregiver descriptions from focus groups and individual interviews, 2) observations from video-recorded play of affected children, 3) descriptions from historic chart review, 4) consultation with patient advocacy groups and international experts, 5) reports from a caregiver advisory board, and 6) literature review. Results: Neurobehavioral symptoms were diverse and categorized as focus/attention, impulsivity/heightened activity, sensation seeking, emotional/behavioral function, social interaction, and sleep. A significant reported challenge was susceptibility to misinterpretation of some behaviors as defiant or aggressive, particularly if physical. Caregiver burden involved social isolation, exhaustion, stress, and financial and vocational strain. These new descriptions will aid in developing quantitative measures of change in neurobehavioral symptoms and family burden. These descriptions will be the foundation of a neurobehavioral rating scale, which is very much needed to aid in patient management and assess interventions for individuals with neuronopathic Hunter syndrome.

Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome.

Hurler syndrome (mucopolysaccharidosis type I, MPS IH) is characterized by a deficiency of alpha-L-iduronidase resulting in progressive multiorgan dysfunction. We sought to determine whether enzyme replacement therapy (ERT) with iduronidase in the peritransplant period affects outcome of hematopoietic stem cell transplantation (HSCT) for MPS IH. Seven children with MPS IH at a median age of 1.5 years at the time of myeloablative HSCT were eligible. All patients had null mutations in IDUA gene. Iduronidase (0.58 mg/kg per dose) was administered intravenously in 11-14 weekly doses before HSCT and 8 weekly doses after HSCT. The infusions were well tolerated. All patients developed antibodies to iduronidase but all engrafted with >90% donor hematopoiesis. A majority of patients had significant pulmonary complications before ERT and HSCT but all are alive and well with a median follow-up of more than 1 year after HSCT. This suggests that ERT prior to HSCT is unlikely to alter engraftment. In addition, morbidity was acceptable, despite a previous history of pulmonary difficulties that suggested that these patients were high risk for these complications. Therefore, we recommend treatment of MPS IH patients with combination of ERT and HSCT therapy to further investigate its potential to enhance outcomes with HSCT.