Exercise intensity- and body region-specific differences in sweating in middle-aged to older men with and without type 2 diabetes.

Type 2 diabetes (T2D) is associated with reduced whole body sweating during exercise-heat stress. However, it is unclear if this impairment is related to exercise intensity and whether it occurs uniformly across body regions. We evaluated whole body (direct calorimetry) and local (ventilated-capsule technique; chest, back, forearm, thigh) sweat rates in physically active men with type 2 diabetes [T2D; aged 59 (7) yr; V̇o2peak 32.3 (7.6) mL·kg-1·min-1; n = 26; HbA1c 5.1%-9.1%] and without diabetes [Control; aged 61 (5) yr; V̇o2peak 37.5 (5.4) mL·kg-1·min-1; n = 26] during light- (∼40% V̇o2peak), moderate- (∼50% V̇o2peak), and vigorous- (∼65% V̇o2peak) intensity exercise (elicited by fixing metabolic heat production at ∼150, 200, 250 W·m-2, respectively) in 40°C, ∼17% relative humidity. Whole body sweating was ∼11% (T2D: Control mean difference [95% confidence interval]: -37 [-63, -12] g·m-2·h-1) and ∼13% (-50 [-76, -25] g·m-2·h-1) lower in the T2D compared with the Control group during moderate- and vigorous- (P ≤ 0.001) but not light-intensity exercise (-21 [-47, 4] g·m-2·h-1; P = 0.128). Consequently, the diabetes-related reductions in whole body sweat rate were 2.3 [1.6, 3.1] times greater during vigorous relative to light exercise (P < 0.001). Furthermore, these diabetes-related impairments in local sweating were region-specific during vigorous-intensity exercise (group × region interaction: P = 0.024), such that the diabetes-related reduction in local sweat rate at the trunk (chest, back) was 2.4 [1.2, 3.7] times greater than that at the limbs (thigh, arm). In summary, when assessed under hot, dry conditions, diabetes-related impairments in sweating are exercise intensity-dependent and greater at the trunk compared with the limbs.NEW & NOTEWORTHY This study evaluates the influence of exercise intensity on decrements in whole body sweating associated with type 2 diabetes. Furthermore, it investigates whether diabetes-related sweating impairments were exhibited uniformly or heterogeneously across body regions. We found that whole body sweating was attenuated in the type 2 diabetes group relative to control participants during moderate- and vigorous-intensity exercise but not light-intensity exercise; impairments were largely mediated by reduced sweating at the trunk rather than the limbs.

Association between haemoglobin A1c and whole-body heat loss during exercise-heat stress in physically active men with type 2 diabetes.

NEW FINDINGS: What is the central question of this study? Is the impairment in heat dissipation during exercise observed in men with type 2 diabetes related to glycaemic control (indexed by glycated haemoglobin; haemoglobin A1c )? What is the main finding and its importance? No association was found between haemoglobin A1c (range: 5.1-9.1%) and whole-body heat loss in men with type 2 diabetes during exercise in the heat. However, individuals with elevated haemoglobin A1c exhibited higher body core temperature and heart rate responses. Thus, while haemoglobin A1c is not associated with heat loss per se, it may still have important implications for physiological strain during exercise. ABSTRACT: Type 2 diabetes is associated with a reduced capacity to dissipate heat. It is unknown whether this impairment is related to glycaemic control (indexed by glycated haemoglobin; haemoglobin A1c ) is unknown. We evaluated the association between haemoglobin A1c and whole-body heat loss (via direct calorimetry), body core temperature, and heart rate in 26 physically active men with type 2 diabetes (43-73 years; HbA1c 5.1-9.1%) during exercise at increasing rates of metabolic heat production (∼150, 200, 250 W m-2 ) in the heat (40°C, ∼17% relative humidity). Haemoglobin A1c was not associated with whole-body heat loss (P = 0.617), nor the increase in core temperature from pre-exercise (P = 0.347). However, absolute core temperature and heart rate were elevated ∼0.2°C (P = 0.014) and ∼6 beats min-1 (P = 0.049), respectively, with every percentage point increase in haemoglobin A1c . Thus, while haemoglobin A1c does not appear to modify diabetes-related reductions in capacity for heat dissipation, it may still have important implications for physiological strain during exercise-heat stress.

Effects of short-term heat acclimation on whole-body heat exchange and local nitric oxide synthase- and cyclooxygenase-dependent heat loss responses in exercising older men.

NEW FINDINGS: What is the central question of this study? Does short-term heat acclimation enhance whole-body evaporative heat loss and augment nitric oxide synthase (NOS)-dependent cutaneous vasodilatation and NOS- and cyclooxygenase (COX)-dependent sweating, in exercising older men? What is the main finding and its importance? Our preliminary data (n = 8) demonstrated that short-term heat acclimation improved whole-body evaporative heat loss, but it did not influence the effects of NOS and/or COX inhibition on cutaneous vasodilatation or sweating in older men during an exercise-heat stress. These outcomes might imply that although short-term heat acclimation enhances heat dissipation in older men, it does not modulate NOS- and COX-dependent control of cutaneous vasodilatation or sweating on the forearm. ABSTRACT: Ageing is associated with decrements in whole-body heat loss (evaporative + dry heat exchange), which might stem from alterations in nitric oxide synthase (NOS)- and cyclooxygenase (COX)-dependent cutaneous vasodilatation and sweating. We evaluated whether short-term heat acclimation would (i) enhance whole-body heat loss primarily by increasing evaporative heat loss, and (ii) augment NOS-dependent cutaneous vasodilatation and NOS- and COX-dependent sweating, in exercising older men. Eight older men [mean (SD) age, 59 (8) years] completed a calorimetry and microdialysis trial before and after 7 days of exercise-heat acclimation. For the calorimetry trials, whole-body evaporative and dry heat exchange were assessed using direct calorimetry during 30 min bouts of cycling at light, moderate and vigorous metabolic heat productions (150, 200 and 250 W/m2 , respectively) in dry heat (40°C, 20% relative humidity). For the microdialysis trials, local cutaneous vascular conductance and sweat rate were assessed during 60 min exercise in the heat (35°C, 20% relative humidity) at four dorsal forearm skin sites treated with lactated Ringer solution (control), NOS inhibitor, COX inhibitor or combined NOS and COX inhibitors, via microdialysis. Evaporative heat loss during moderate (P = 0.036) and vigorous (P = 0.021) exercise increased after acclimation. Inhibition of NOS alone reduced cutaneous vascular conductance to a similar extent before and after acclimation (P < 0.040), whereas separate and combined NOS and COX inhibition had no significant effects on sweating relative to the control site (P = 0.745). Our preliminary results might suggest that short-term heat acclimation improves evaporative heat loss, but does not significantly modulate the contributions of NOS or COX to cutaneous vasodilatation or sweating on the forearm in older men during an exercise-heat stress.

Evidence for age-related differences in heat acclimatisation responsiveness.

NEW FINDINGS: What is the central question of this study? Repeated heat exposure during the summer months can enhance heat loss in humans (seasonal heat acclimatisation), but does the magnitude of that enhancement differ between young and older adults when assessed during passive heat exposure? What is the main finding and its importance? While seasonal heat acclimatisation enhanced evaporative heat loss (i.e. sweating) in both young and older adults, those improvements led to a greater reduction in body heat storage in older adults. These outcomes indicate that heat acclimatisation may confer greater thermoregulatory benefits with increasing age. ABSTRACT: Repeated heat exposure throughout summer can enhance heat loss in humans (seasonal heat acclimatisation), although the effect of ageing on those improvements remains unclear. We therefore sought to assess thermoregulatory function in young and older adults during environmental heat exposure prior to and following seasonal heat acclimatisation, hypothesizing that the magnitude of adaptation would be greater in older relative to young adults. To achieve this, 14 young (19-27 years) and 10 older adults (55-72 years), who resided in a temperate humid-continental climate, completed a 3 h resting heat exposure (44°C, ∼30% relative humidity) in the winter-spring months as part of a larger investigation (pre-acclimatisation), before being re-evaluated using the same heat stress test following the summer months (post-acclimatisation). Whole-body dry and evaporative heat exchange, and metabolic rate were measured throughout using direct and indirect calorimetry (respectively), and used to quantify body heat storage (metabolic rate + dry heat gain - evaporative heat loss). Evaporative heat loss increased in both groups following acclimatisation, but those improvements led to a decrease in body heat storage in older (mean difference (95% CI); 213 (295, 131) kJ; P < 0.001), but not young adults (-25 (-94, 44) kJ; P = 0.458). Thus, body heat storage was greater in older compared to young adults before (222 (123, 314) kJ; P < 0.001), but not following acclimatisation (34 (-55, 123) kJ; P = 0.433). Although there is a need for larger and more controlled confirmatory studies, our findings indicate that seasonal heat acclimatisation may induce greater thermoregulatory adaptation in older compared to young adults.

Fitness-related differences in the rate of whole-body evaporative heat loss in exercising men are heat-load dependent.

NEW FINDINGS: What is the central question of this study? Aerobic fitness modulates heat loss, but the heat-load threshold at which fitness-related differences in heat loss occur in young healthy men remains unclear. What is the main finding and its importance? We demonstrate using direct calorimetry that aerobic fitness modulates heat loss in a heat-load-dependent manner, with fitness-related differences occurring between young men who have low and high fitness when the heat load is ∼≥500 W. Although aerobic fitness has been known for some time to modulate heat loss, our findings define the precise heat-load threshold at which fitness-related differences occur. The effect of aerobic fitness (defined as rate of peak oxygen consumption) on heat loss during exercise is thought to be related to the level of heat stress. However, it remains unclear at what combined exercise and environmental (net) heat-load threshold these fitness-related differences occur. To identify this, we assessed whole-body heat exchange (dry and evaporative) by direct calorimetry in young (22 ± 3 years) men matched for physical characteristics with low (Low-fit; 39.8 ± 2.5 ml O2  kg-1  min-1 ), moderate (Mod-fit; 50.9 ± 1.2 ml O2  kg-1  min-1 ) and high aerobic fitness (High-fit; 62.0 ± 4.4 ml O2  kg-1  min-1 ; each n = 8), during three 30 min bouts of cycling in dry heat (40°C, 12% relative humidity) at increasing rates of metabolic heat production of 300 (Ex1), 400 (Ex2) and 500 W (Ex3), each followed by a 15 min recovery period. Each group was exposed to a similar net heat load (metabolic plus ∼100 W dry heat gain; P = 0.83) during each exercise bout [∼400 (Ex1), ∼500 (Ex2) and ∼600 W (Ex3); P < 0.01]. Although evaporative heat loss was similar between groups during Ex1 (P = 0.33), evaporative heat loss was greater in the High-fit (Ex2, 466 ± 21 W; Ex3, 557 ± 26 W) compared with the Low-fit group (Ex2, 439 ± 22 W; Ex3, 511 ± 20 W) during Ex2 and Ex3 (P ≤ 0.03). Conversely, evaporative heat loss for the Mod-fit group did not differ from either the High-fit or Low-fit group during all exercise bouts (P ≥ 0.09). We demonstrate that aerobic fitness modulates heat loss in a heat-load-dependent manner, such that young, highly fit men display greater heat-loss capacity only at heat loads ∼≥500 W compared with their lesser trained counterparts.

Fitness-related differences in the rate of whole-body total heat loss in exercising young healthy women are heat-load dependent.

NEW FINDINGS: What is the central question of this study? Aerobic fitness modulates heat loss, albeit the heat load at which fitness-related differences occur in young healthy women remains unclear. What is the main finding and its importance? We demonstrate using direct calorimetry that fitness modulates heat loss in a heat-load dependent manner, with differences occurring between young women of low and high fitness and matched physical characteristics when the metabolic heat load is at least 400 W in hot, dry conditions. Although fitness has been known for some time to modulate heat loss, our findings define the metabolic heat load at which fitness-related differences occur. ABSTRACT: Aerobic fitness has recently been shown to alter heat loss capacity in a heat-load dependent manner in young men. However, given that sex-related differences in heat loss capacity exist, it is unclear whether this response is consistent in women. We therefore assessed whole-body total heat loss in young (21 ± 3 years old) healthy women matched for physical characteristics, but with low (low-fit; 35.8 ± 4.5 ml O2  kg-1  min-1 ) or high aerobic fitness (high-fit; 53.1 ± 5.1 ml O2  kg-1  min-1 ; both n = 8; indexed by peak oxygen consumption), during three 30 min bouts of cycling performed at increasing rates of metabolic heat production of 250 (Ex1), 325 (Ex2) and 400 W (Ex3), each separated by a 15 min recovery, in hot, dry conditions (40°C, 11% relative humidity). Whole-body total heat loss (evaporative ± dry heat exchange) and metabolic heat production were measured using direct and indirect calorimetry, respectively. Body heat content was measured as the temporal summation of heat production and loss. Total heat loss did not differ during Ex1 (low-fit, 215 ± 16 W; high-fit, 231 ± 20 W; P > 0.05) and Ex2 (low-fit, 278 ± 15 W; high-fit, 301 ± 20 W; P > 0.05), but was lower in the low-fit (316 ± 21 W) compared with the high-fit women (359 ± 32 W) during Ex3 (P < 0.01). Consequently, the low-fit group stored 1.3-fold more heat (429 ± 61 kJ) throughout the three exercise bouts relative to the high-fit group (330 ± 113 kJ; P < 0.05). We show that aerobic fitness independently modulates heat loss capacity during exercise in hot, dry conditions in women separated by a peak oxygen consumption of ∼17 ml O2  kg-1  min-1 starting at a metabolic heat load of 400 W.

Oxidative stress does not influence local sweat rate during high-intensity exercise.

NEW FINDINGS: What is the central question of this study? We evaluated whether oxidative stress attenuates the contribution of nitric oxide to sweating during high-intensity exercise. What is the main finding and its importance? In contrast to our previous report of an oxidative stress-mediated reduction in nitric oxide-dependent cutaneous vasodilatation in this cohort during intense exercise, we demonstrated no influence of local ascorbate administration on the sweating response during moderate- (∼51% peak oxygen uptake) or high-intensity exercise (∼72% peak oxygen uptake). These new findings provide important mechanistic insight into how exercise-induced oxidative stress impacts sudomotor activity. Nitric oxide (NO)-dependent sweating is diminished during high- but not moderate-intensity exercise. We evaluated whether this impairment stems from increased oxidative stress during high-intensity exercise. On two separate days, 11 young (24 ± 4 years) men cycled in the heat (35°C) at a moderate [500 W; 52 ± 6% peak oxygen uptake (V̇O2 peak )] or high (700 W; 71 ± 5% V̇O2 peak ) rate of metabolic heat production. Each session included two 30 min exercise bouts separated by a 20 min recovery period. Local sweat rate was monitored at four forearm skin sites continuously perfused via intradermal microdialysis with the following: (i) lactated Ringer solution (Control); (ii) 10 mm ascorbate (Ascorbate; non-selective antioxidant); (iii) 10 mm NG -nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor); or (iv) 10 mm ascorbate plus 10 mm l-NAME (Ascorbate + l-NAME). During moderate exercise, sweat rate was attenuated at the l-NAME and Ascorbate + l-NAME sites (both ∼1.0 mg min-1  cm-2 ; all P < 0.05) but not at the Ascorbate site (∼1.1 mg min-1  cm-2 ; both P ≥ 0.28) in comparison to the Control site (∼1.1 mg min-1  cm-2 ). However, no differences were observed between treatment sites (∼1.4 mg min-1  cm-2 ; P = 0.75) during high-intensity exercise. We conclude that diminished NO-dependent sweating during intense exercise occurs independent of oxidative stress.

Heart rate variability during high heat stress: a comparison between young and older adults with and without Type 2 diabetes.

We examined whether older individuals with and without Type 2 diabetes (T2D) experience differences in heart rate variability (HRV) during a 3-h exposure to high heat stress compared with young adults. Young (Young; n = 22; 23 ± 3 yr) and older individuals with (T2D; n = 11; 59 ± 9 yr) and without (Older; n = 25; 63 ± 5 yr) T2D were exposed to heat stress (44°C, 30% relative humidity) for 3 h. Fifty-five HRV measures were assessed for 15 min at baseline and at minutes 82.5-97.5 (Mid) and minutes 165-180 (End) during heat stress. When compared with Young, a similar number of HRV indices were significantly different (P < 0.05) in Older (Baseline: 35; Mid: 29; End: 32) and T2D (Baseline: 31; Mid: 30; End: 27). In contrast, the number of HRV indices significantly different (P < 0.05) between Older and T2D were far fewer (Baseline: 13, Mid: 1, End: 3). Within-group analyses demonstrated a greater change in the Young group's HRV during heat stress compared with Older and T2D; the number of significantly different (P < 0.05) HRV indices between baseline and End were 42, 29, and 20, for Young, Older, and T2D, respectively. Analysis of specific HRV domains suggest that the Young group experienced greater sympathetic activity during heat stress compared with Older and T2D. In conclusion, when compared with young, older individuals with and without T2D demonstrate low HRV at baseline and less change in HRV (including an attenuated sympathetic response) during 3 h high heat stress, potentially contributing to impaired thermoregulatory function.

The physical demands of electrical utilities work in North America.

We assessed the physical demands associated with electrical utilities work in North America and how they influence the level of thermal and cardiovascular strain experienced. Three common job categories were monitored as they are normally performed in thirty-two electrical utility workers: (i) Ground Work (n = 11), (ii) Bucket Work (n = 9), and (iii) Manual Pole Work (n = 12). Video analysis was performed to determine the proportion of the work monitoring period (duration: 187 ± 104 min) spent at different levels of physical effort (i.e., rest as well as light, moderate and heavy effort). Core and skin temperatures as well as heart rate were measured continuously. On average, workers spent 35.9 ± 15.9, 36.8 ± 17.8, 24.7 ± 12.8, and 2.6 ± 3.3% of the work period at rest and performing work classified as light, moderate, and heavy physical effort, respectively. Moreover, a greater proportion of the work period was spent performing heavy work in Ground Work (1.6 ± 1.4%) relative to Bucket Work (0.0 ± 0.0%; P<0.01) and in Manual Pole Climbing (5.5 ± 3.6%) in comparison to both other work job (both P≤0.03). Furthermore, the proportion of time spent during work classified as heavy physical effort was positively correlated to the mean (r = 0.51, P<0.01) and peak (r = 0.42, P = 0.02) core temperatures achieved during the work period as well as the mean heart rate response (presented as a percentage of heart rate reserve; r = 0.40, P = 0.03). Finally, mean and peak core temperatures and mean heart rate responses increased from the first to the second half of the work shift; however, no differences in the proportion of the work spent at the different intensity classifications were observed. We show that Manual Pole Work is associated with greater levels of physical effort compared to Ground or Bucket Work. Moreover, we suggest that the proportion of time spent performing work classified as heavy physical exertion is related to the level of thermal and cardiovascular strain experienced and that workers may not be employing self-pacing as a strategy to manage their level of physiological strain.

An Evaluation of the Physiological Strain Experienced by Electrical Utility Workers in North America.

The purpose of this study was to assess the physiological strain experienced by North American electrical utility workers during the performance of their normal work duties in heat stressed conditions. Three common job categories were monitored as they are normally performed in 32 electrical utility workers: (i) Ground Work (n = 11); (ii) Bucket Work (n = 9); and (iii) Manual Pole Work (n = 12). Worker hydration status (urine specific gravity (USG)) was measured prior to and following the work monitoring period (duration: 187 ± 104 min). Core and skin temperatures as well as heart rate were measured continuously. Physiological Strain Index (PSI) was calculated from the measurements of core temperature and heart rate. Prior to the start of the work shift, 38% of workers were euhydrated (USG < 1.020; n = 12) whereas the majority of workers were dehydrated (USG > 1.020; prevalence: 75%; p < 0.01) following work. The overall mean and peak core temperatures for all monitored workers were 37.9 ± 0.3 °C and 38.3 ± 0.5 °C, respectively. When responses were compared between job categories, greater mean and peak increases in core temperature were observed in Manual Pole Work relative to the other job categories (both p < 0.04). In fact, six workers performing Manual Pole Work achieved core temperatures in excess of 38.5 °C, while only one other worker surpassed this threshold in Bucket Work. The high levels of thermal strain were paralleled by elevated mean and peak heart rate and PSI responses, which were greater in Manual Pole Work in comparison to the other job categories (all p ≤ 0.05). Furthermore, two workers performing Manual Pole Work achieved severely elevated core temperatures reaching or exceeding 39.5 °C along with prolonged periods of near maximal heart rate responses (i.e., >90% of heart rate reserve). We report elevated levels of thermal and cardiovascular strain in electrical utility workers during work in the heat and potentially dangerous levels of hyperthermia during particularly strenuous work.

The Influence of Arc-Flash and Fire-Resistant Clothing on Thermoregulation during Exercise in the Heat.

We evaluated the effect of arc-flash and fire-resistant (AFR) clothing ensembles (CE) on whole-body heat dissipation during work in the heat. On 10 occasions, 7 males performed four 15-min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C), each separated by 15-min of recovery. Whole-body heat loss and metabolic heat production were measured by direct and indirect calorimetry, respectively. Body heat storage was calculated as the temporal summation of heat production and heat loss. Responses were compared in a semi-nude state and while wearing two CE styles: (1) single-piece (coveralls) and (2) two-piece (workpant + long-sleeve shirt). For group 1, there was one non-AFR single-piece CE (CE1STD) and three single-piece CE with AFR properties (CE2AFR, CE3AFR, CE4AFR). For group 2, there was one non-AFR two-piece CE (CE5STD) and four two-piece CE with AFR properties (CE6AFR, CE7AFR, CE8AFR, CE9AFR). The workpants for CE6AFR were not AFR-rated, while a cotton undershirt was also worn for conditions CE8AFR and CE9AFR and for all single-piece CE. Heat storage for all conditions (CE1STD: 328 ± 55, CE2AFR: 335 ± 87, CE3AFR: 309 ± 95, CE4AFR: 403 ± 104, CE5STD: 253 ± 78, CE6AFR: 268 ± 89, CE7AFR: 302 ± 70, CE8AFR: 360 ± 36, CE9AFR: 381 ± 99 kJ) was greater than the semi-nude state (160 ± 124 kJ) (all p ≤ 0.05). No differences were measured between single-piece uniforms (p = 0.273). Among the two-piece uniforms, heat storage was greater for CE8AFR and CE9AFR relative to CE5STD and CE6AFR (all p ≤ 0.05), but not CE7AFR (both p > 0.05). Differences between clothing styles were measured such that greater heat storage was observed in both CE1STD and CE2-4AFR relative to CE5STD. Further, heat storage was greater in CE2AFR and CE4AFR relative to CE6AFR, while it was greater in CE4AFR compared to CE7AFR. Body heat storage during work in the heat was not influenced by the use of AFR fabrics in the single- or two-piece uniforms albeit less heat was stored in the two-piece uniforms when no undershirt was worn. However, heat storage was comparable between clothing styles when an undershirt was worn with the two-piece uniform.

Changes in heart rate variability during the induction and decay of heat acclimation.

PURPOSE: We evaluated the changes in core temperature, heart rate, and heart rate variability (HRV) during the induction and decay of heat acclimation. METHODS: Ten males (23 ± 3 years; 79.5 ± 3.5 kg; 15.2 ± 4.5 percent body fat; 51.13 ± 4.61 mLO(2)∙kg(-1)∙min(-1) peak oxygen uptake) underwent a 14-day heat acclimation protocol comprising of 90-min cycling at ~50 % peak oxygen uptake at 40 °C and ~20 % relative humidity. Core temperature, heart rate, and 102 HRV measures were recorded during a heat tolerance test conducted at baseline (day 0) and at the end of the induction (day 14) and decay (day 28) phases. RESULTS: Heat acclimation resulted in significantly reduced core temperature [rectal (χ (2) = 1298.14, p < 0.001); esophageal (χ (2) = 1069.88, p < 0.001)] and heart rate (χ (2) = 1230.17, p < 0.001). Following the decay phase, 26, 40, and 60 % of the heat acclimation-induced reductions in rectal temperature, esophageal temperature, and heart rate, respectively, were lost. Heat acclimation was accompanied by profound and broad changes in HRV: at the end of the induction phase, 75 of the 102 variability measures computed were significantly different (p < 0.001), compared to only 47 of the 102 at the end of the decay phase. CONCLUSIONS: Heat acclimation is accompanied by reduced core temperature, significant bradycardia, and marked alterations in HRV, which we interpret as being related to vagal dominance. The observed changes in core temperature persist for at least 2 weeks of non-exposure to heat, while the changes in heart rate and HRV decay faster and are only partly evident after 2 weeks of non-exposure to heat.

Technical-tactical behavior analysis of general duty police officers during non-compliant suspect apprehensions: A novel approach to establish minimum force requirements.

BACKGROUND: While effective apprehensions of non-compliant suspects are central to public safety, the minimal force needed to transition a suspect from standing to the ground, vital for apprehension success, has not been established. OBJECTIVE: To examine the technical-tactical behaviors of general duty police officers during simulated apprehensions and quantify the minimum force required to destabilize non-compliant suspects. METHODS: Task simulations conducted with 91 officers were analyzed to identify common grappling movements, strikes, control tactics, and changes in body posture. A separate assessment of 55 male officers aimed to determine the minimum force required for destabilization in five body regions (wrist, forearm, shoulder, mid-chest, and mid-back). Data are presented as mean±standard deviation. RESULTS: On average, apprehensions took 7.3±3.2 seconds. While all officers used grappling movements (100%) and the majority employed control tactics (75%), strikes were seldom used (4%). Apprehensions typically began with a two-handed pull (97%; Contact Phase), 55% then attempted an arm bar takedown, followed by a two-handed cross-body pull (68%; Transition/Control Phase), and a two-handed push to the ground (19%; Ground Phase). All officers began in the upright posture, with most shifting to squat (75%), kneel (58%), or bent (45%) postures to complete the apprehension. The minimum force required to disrupt balance differed across body regions (wrist: 54±12 kg; forearm: 49±12 kg; shoulder: 42±10 kg; mid-chest: 44±11 kg; mid-back: 30±7 kg, all P < 0.05), except between the shoulder and chest (P = 0.19). CONCLUSION: These findings provide insights that can enhance the design and accuracy of future apprehension evaluations and inform the optimization of law enforcement physical employment standards.

Structure-based design of novel HCV NS5B thumb pocket 2 allosteric inhibitors with submicromolar gt1 replicon potency: discovery of a quinazolinone chemotype.

We describe the structure-based design of a novel lead chemotype that binds to thumb pocket 2 of HCV NS5B polymerase and inhibits cell-based gt1 subgenomic reporter replicons at sub-micromolar concentrations (EC50<200nM). This new class of potent thumb pocket 2 inhibitors features a 1H-quinazolin-4-one scaffold derived from hybridization of a previously reported, low affinity thiazolone chemotype with our recently described anthranilic acid series. Guided by X-ray structural information, a key NS5B-ligand interaction involving the carboxylate group of anthranilic acid based inhibitors was replaced by a neutral two-point hydrogen bonding interaction between the quinazolinone scaffold and the protein backbone. The in vitro ADME and in vivo rat PK profile of representative analogs are also presented and provide areas for future optimization of this new class of HCV polymerase inhibitors.

Physiological Demands of Basic Fire Management Tasks in Members of the Canadian Armed Forces: A Pilot Study.

INTRODUCTION: Members of the Canadian Armed Forces (CAF) are required to meet the minimum standards of the Fitness for Operational Requirements of CAF Employment (FORCE) job-based simulation test (JBST) and must possess the capacity to perform other common essential tasks. One of those tasks is to perform basic fire management tasks during fire emergencies to mitigate damage and reduce the risk of injuries and/or death until professional firefighters arrive at the scene. To date however, the physiological demands of common firefighting tasks have mostly been performed on professional firefighters, thus rendering the transferability of the demands to the general military population unclear. This pilot study aimed to quantify, for the first time, the physiological demands of basic fire management tasks in the military, to determine if they are reflected in the FORCE JBST minimum standard. We hypothesized that the physiological demands of basic fire management tasks within the CAF are below the physiological demands of the FORCE JBST minimum standard, and as such, be lower than the demands of professional firefighting. MATERIALS AND METHODS: To achieve this, 21 CAF members (8 females; 13 males; mean [SD] age: 33 [10] years; height: 174.5 [10.5] cm; weight: 85.4 [22.1] kg, estimated maximal oxygen uptake [$\dot V$O2peak]: 44.4 (7.4) mL kg-1 min-1) participated in a realistic, but physically demanding, JBST developed by CAF professional firefighting subject matter experts. The actions included lifting, carrying, and manipulating a 13-kg powder fire extinguisher and connecting, coupling, and dragging a 38-mm fire hose over 30 m. The rate of oxygen uptake ($\dot V$O2), heart rate, and percentage of heart rate reserve were measured continuously during two task simulation trials, which were interspersed by a recovery period. Rating of perceived exertion (6-no exertion; 20-maximal exertion) was measured upon completion of both task simulations. Peak $\dot V$O2 ($\dot V$O2peak) was estimated based on the results of the FORCE JBST. RESULTS: The mean (SD) duration of both task simulation trials was 3:39 (0:19) min:s, whereas the rest period in between both trials was 62 (19) minutes. The mean O2 was 21.1 (4.7) mL kg-1 min-1 across trials, which represented 52.1 (12.2) %$\dot V$O2peak and ∼81% of the FORCE JBST. This was paralleled by a mean heart rate of 136 (18) beats min-1, mean percentage of heart rate reserve of 61.2 (10.8), and mean rating of perceived exertion of 11 ± 2. Other physical components of the JBST consisted of lifting, carrying, and manipulating a 13-kg load for ∼59 seconds, which represents 65% of the load of the FORCE JBST. The external resistance of the fire hose drag portion increased up to 316 N, translating to a total of 6205 N over 30 m, which represents 96% of the drag force measured during the FORCE JBST. CONCLUSIONS: Our findings demonstrate that the physiological demands of basic fire management tasks in the CAF are of moderate intensity, which are reflected in the CAF physical fitness standard. As such, CAF members who achieve the minimum standard on the FORCE JBST are deemed capable of physically performing basic fire management tasks during fire emergencies.

Heat tolerance and the validity of occupational heat exposure limits in women during moderate-intensity work.

To mitigate excessive rises in core temperature (>1 °C) in non-heat acclimatized workers, the American Conference of Governmental Industrial Hygienists (ACGIH) provides heat stress limits (Action Limit Values; ALV), defined by the wet-bulb globe temperature (WBGT) and a worker's metabolic rate. However, since these limits are based on data from men, their suitability for women remains unclear. We therefore assessed core temperature and heart rate in men (n = 19; body surface area-to-mass ratio: 250 (SD 17) cm2/kg) and women (n = 15; body surface area-to-mass ratio: 268 (SD 24) cm2/kg) aged 18-45 years during 180 min of walking at a moderate metabolic rate (200 W/m2) in WBGTs below (16 and 24 °C) and above (28 and 32 °C) ACGIH ALV. Sex did not significantly influence (i) rises in core temperature, irrespective of WBGT, (ii) the proportion of participants with rises in core temperature >1 °C in environments below ACGIH limits, and (iii) work duration before rises in core temperature exceeded 1 °C or volitional termination in environments above ACGIH limits. Although further studies are needed, these findings indicate that for the purpose of mitigating rises in core temperature exceeding recommended limits (>1 °C), ACGIH guidelines have comparable effectiveness in non-heat acclimatized men and women during moderate-intensity work. Novelty: Sex did not appreciably influence thermal strain nor the proportion of participants with core temperatures exceeding recommended limits. Sex did not significantly influence tolerance to uncompensable heat stress. Despite originating from data obtained in only men, current occupational heat stress guidance offered comparable effectiveness in men and women.

Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation.

Huntington's disease (HD) is caused by an expansion of the CAG trinucleotide repeat domain in the huntingtin gene that results in expression of a mutant huntingtin protein (mHTT) containing an expanded polyglutamine tract in the amino terminus. A number of therapeutic approaches that aim to reduce mHTT expression either locally in the CNS or systemically are in clinical development. We have previously described sensitive and selective assays that measure human HTT proteins either in a polyglutamine-independent (detecting both mutant expanded and non-expanded proteins) or in a polyglutamine length-dependent manner (detecting the disease-causing polyglutamine repeats) on the electrochemiluminescence Meso Scale Discovery detection platform. These original assays relied upon polyclonal antibodies. To ensure an accessible and sustainable resource for the HD field, we developed similar assays employing monoclonal antibodies. We demonstrate that these assays have equivalent sensitivity compared to our previous assays through the evaluation of cellular and animal model systems, as well as HD patient biosamples. We also demonstrate cross-site validation of these assays, allowing direct comparison of studies performed in geographically distinct laboratories.