Evidence of heat sensitivity in people with Parkinson's disease.

Examining how heat affects people with Parkinson's disease is essential for informing clinical decision-making, safety, well-being, and healthcare planning. While there is evidence that the neuropathology associated with Parkinson's disease affects thermoregulatory mechanisms, little attention has been given to the association of heat sensitivity to worsening symptoms and restricted daily activities in people with this progressive disease. Using a cross-sectional study design, we examined the experiences of people diagnosed with Parkinson's disease in the heat. Two-hundred and forty-seven people completed an online survey (age: 66.0 ± 9.2 years; sex: male = 102 (41.3%), female = 145 (58.7%)), of which 195 (78.9%) reported becoming more sensitive to heat with Parkinson's disease. Motor and nonmotor symptoms worsened with heat in 182 (73.7%) and 203 (82.2%) respondents, respectively. The most commonly reported symptoms to worsen included walking difficulties, balance impairment, stiffness, tremor, fatigue, sleep disturbances, excess sweating, difficulty concentrating, and light-headedness when standing. Concerningly, over half indicated an inability to work effectively in the heat, and nearly half reported that heat impacted their ability to perform household tasks and social activities. Overall, heat sensitivity was common in people with Parkinson's disease and had a significant impact on symptomology, day-to-day activities and quality of life.

The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity.

Nitric oxide (NO) is an important signaling molecule that is involved in a wide range of physiological and pathological events in biology. Metal coordination chemistry, especially with iron, is at the heart of many biological transformations involving NO. A series of heme proteins, nitric oxide synthases (NOS), soluble guanylate cyclase (sGC), and nitrophorins, are responsible for the biosynthesis, sensing, and transport of NO. Alternatively, NO can be generated from nitrite by heme- and copper-containing nitrite reductases (NIRs). The NO-bearing small molecules such as nitrosothiols and dinitrosyl iron complexes (DNICs) can serve as an alternative vehicle for NO storage and transport. Once NO is formed, the rich reaction chemistry of NO leads to a wide variety of biological activities including reduction of NO by heme or non-heme iron-containing NO reductases and protein post-translational modifications by DNICs. Much of our understanding of the reactivity of metal sites in biology with NO and the mechanisms of these transformations has come from the elucidation of the geometric and electronic structures and chemical reactivity of synthetic model systems, in synergy with biochemical and biophysical studies on the relevant proteins themselves. This review focuses on recent advancements from studies on proteins and model complexes that not only have improved our understanding of the biological roles of NO but also have provided foundations for biomedical research and for bio-inspired catalyst design in energy science.

Heat Stress Management in the Military: Wet-Bulb Globe Temperature Offsets for Modern Body Armor Systems.

OBJECTIVE: The aim of this study was to model the effect of body armor coverage on body core temperature elevation and wet-bulb globe temperature (WBGT) offset. BACKGROUND: Heat stress is a critical factor influencing the health and safety of military populations. Work duration limits can be imposed to mitigate the risk of exertional heat illness and are derived based on the environmental conditions (WBGT). Traditionally a 3°C offset to WBGT is recommended when wearing body armor; however, modern body armor systems provide a range of coverage options, which may influence thermal strain imposed on the wearer. METHOD: The biophysical properties of four military clothing ensembles of increasing ballistic protection coverage were measured on a heated sweating manikin in accordance with standard international criteria. Body core temperature elevation during light, moderate, and heavy work was modeled in environmental conditions from 16°C to 34°C WBGT using the heat strain decision aid. RESULTS: Increasing ballistic protection resulted in shorter work durations to reach a critical core temperature limit of 38.5°C. Environmental conditions, armor coverage, and work intensity had a significant influence on WBGT offset. CONCLUSION: Contrary to the traditional recommendation, the required WBGT offset was >3°C in temperate conditions (<27°C WBGT), particularly for moderate and heavy work. In contrast, a lower WBGT offset could be applied during light work and moderate work in low levels of coverage. APPLICATION: Correct WBGT offsets are important for enabling adequate risk management strategies for mitigating risks of exertional heat illness.

Monitoring heat strain: the effect of sensor type and location on single-site and mean skin temperature during work in the heat.

PURPOSE: Elevations in skin temperature and heat strain reduce tolerance to work in the heat. This study assessed agreement between mean (eight sites) and single-site skin temperature, measured by a conductive or infrared sensor, during exercise in the heat. METHODS: Twelve males (age: 24.2 ± 3.7 years; height: 180 ± 6.5 cm; body mass: 82.9 ± 9.5 kg; body fat: 16.0 ± 6.5%) volunteered to participate in two trials. Thirty minutes of seated rest was followed by 60 min of treadmill walking (4.5 km·h-1, 1%) inside an environmental chamber (35.5 ± 0.2 °C dry bulb, 50.7 ± 2.5% relative humidity) wearing either an athletic (ATH: t-shirt, shorts, shoes) or a chemical protective ensemble (CPE: ATH plus coverall and respirator). Skin temperature was measured on the axilla with a conductive sensor (Tsk-C) and an infrared sensor (Tsk-I) and compared to mean skin temperature ([Formula: see text] 8-site conductive sensors). Rectal temperature and heart rate were measured and used to calculate the adaptive physiological strain index (aPSI). RESULTS: Skin temperature on the chest, scapula, and thigh showed acceptable agreement with [Formula: see text] (mean difference < 0.5 °C and limits of agreement ± 1.0 °C) in both ATH and CPE. Skin temperature on the axilla overestimated [Formula: see text] in ATH (Tsk-C: 1.5 ± 0.8 °C; Tsk-I: 2.2 ± 1.2 °C) and CPE (Tsk-C: 1.1 ± 0.9 °C; Tsk-I: 1.8 ± 1.1 °C). Significant differences (p < 0.001) were observed in aPSI using Tsk-I (ATH: 5.7 ± 1.0, CPE: 8.3 ± 1.1) and Tsk-C (ATH: 5.4 ± 1.0, CPE 7.8 ± 1.0) compared to [Formula: see text] (ATH: 5.2 ± 1.0, CPE: 7.4 ± 1.0). CONCLUSION: The overestimate of mean skin temperature had a significant influence on the aPSI, which has important implications for real-time monitoring and risk management of personnel working in hot environments.

Comparison of two mathematical models for predicted human thermal responses to hot and humid environments.

PURPOSE: We compared the accuracy and design of two thermoregulatory models, the US Army's empirically designed Heat Strain Decision Aid (HSDA) and the rationally based Health Risk Prediction (HRP) for predicting human thermal responses during exercise in hot and humid conditions and wearing chemical protective clothing. METHODS: Accuracy of the HSDA and HRP model predictions of core body and skin temperature (Tc, Ts) were compared to each other and relative to measured outcomes from eight male volunteers (age 24 ± 6 years; height 178 ± 5 cm; body mass 76.6 ± 8.4 kg) during intermittent treadmill marching in an environmental chamber (air temperature 29.3 ± 0.1 °C; relative humidity 56 ± 1%; wind speed 0.4 ± 0.1 m∙s-1) wearing three separate chemical protective ensembles. Model accuracies and precisions were evaluated by the bias, mean absolute error (MAE), and root mean square error (RMSE) compared to observed data mean ± SD and the calculated limits of agreement (LoA). RESULTS: Average predictions of Tc were comparable and acceptable for each method, HSDA (Bias 0.02 °C; MAE 0.18 °C; RMSE 0.21 °C) and HRP (Bias 0.10 °C; MAE 0.25 °C; RMSE 0.34 °C). The HRP averaged predictions for Ts were within an acceptable agreement to observed values (Bias 1.01 °C; MAE 1.01 °C; RMSE 1.11 °C). CONCLUSION: Both HSDA and HRP acceptably predict Tc and HRP acceptably predicts Ts when wearing chemical protective clothing during exercise in hot and humid conditions.

Utilizing Drones to Restore and Maintain Radio Communication During Search and Rescue Operations.

INTRODUCTION: The ability of rescuers to maintain contact with incident command (IC) and each other is a critical component of search and rescue (SAR) operations. When rescuers lose radio communication with operation leaders, the effectiveness of operations may be substantially affected. This often occurs owing to the limitations of standard communications equipment in difficult terrain or when victims are beyond line-of-sight. This study investigates the viability of using an aerial drone-repeater system configuration to restore and maintain radio communications between IC and deployed rescuers. METHODS: SAR operators in Southern Utah identified 10 areas where radio communication is compromised during live rescue operations. Trained SAR personnel were deployed to these areas in a mock exercise. After confirmed loss of communication, a repeater-equipped aerial drone was piloted 122 m above IC to restore communication. Once restored, communication was assessed at regular intervals for the duration of the mock deployment. RESULTS: In all 10 areas tested, communication was successfully restored. In all cases, once communication was restored, no additional loss of radio contact occurred. The time between communication loss and restoration across the 10 scenarios was 6.5±1.1 (4.4-9.3) min (mean±SD with range). CONCLUSIONS: This method of restoring radio communication among SAR personnel could drastically improve the ability to assist victims and help mitigate the risks faced by rescuers. SAR leaders should be made aware of the useful applications of drones during SAR operations, especially in instances where communication is compromised.

Mechanism and regulation of ferrous heme-nitric oxide (NO) oxidation in NO synthases.

Nitric oxide (NO) synthases (NOSs) catalyze the formation of NO from l-arginine. We have shown previously that the NOS enzyme catalytic cycle involves a large number of reactions but can be characterized by a global model with three main rate-limiting steps. These are the rate of heme reduction by the flavin domain (kr ), of dissociation of NO from the ferric heme-NO complex (kd ), and of oxidation of the ferrous heme-NO complex (kox). The reaction of oxygen with the ferrous heme-NO species is part of a futile cycle that does not directly contribute to NO synthesis but allows a population of inactive enzyme molecules to return to the catalytic cycle, and thus, enables a steady-state NO synthesis rate. Previously, we have reported that this reaction does involve the reaction of oxygen with the NO-bound ferrous heme complex, but the mechanistic details of the reaction, that could proceed via either an inner-sphere or an outer-sphere mechanism, remained unclear. Here, we present additional experiments with neuronal NOS (nNOS) and inducible NOS (iNOS) variants (nNOS W409F and iNOS K82A and V346I) and computational methods to study how changes in heme access and electronics affect the reaction. Our results support an inner-sphere mechanism and indicate that the particular heme-thiolate environment of the NOS enzymes can stabilize an N-bound FeIII-N(O)OO- intermediate species and thereby catalyze this reaction, which otherwise is not observed or favorable in proteins like globins that contain a histidine-coordinated heme.

Model Complexes Elucidate the Role of the Proximal Hydrogen-Bonding Network in Cytochrome P450s.

Cytochrome (Cyt) P450s are an important class of enzymes with numerous functions in nature. The unique reactivity of these enzymes relates to their heme b active sites with an axially bound, deprotonated cysteine (a "cysteinate") ligand (chemically speaking a thiolate). The heme-thiolate active sites further contain a number of conserved hydrogen-bonds (H-bonds) to the bound cysteinate ligand, which have been proposed to tune and stabilize the Fe-S bond. In this work, we present the low-temperature preparation of five ferric heme-thiolate nitric oxide (NO) model complexes that contain one tunable hydrogen-bond to the bound thiolate ligand. We show that the presence of a H-bond has a dramatic effect in stabilizing the thiolate ligand against direct reaction with NO. This observation reinforces the important protective role of H-bonds in Cyt P450s. We further demonstrate that H-bond strength tunes thiolate donor strength, which, in turn, controls the N-O and Fe-NO stretching frequencies and hence, bond strengths. We observe a direct correlation between the Fe-NO and N-O stretching frequencies, indicative of a thiolate σ-trans effect (interaction). Here, very small changes in H-bond strength lead to a surprisingly large effect on the FeNO unit. This result implies that subtle changes in the Cys-pocket of a Cyt P450 can strongly affect reactivity. Importantly, using the Fe-NO/N-O correlation established here, the thiolate donor strength in heme-thiolate enzyme active sites and model complexes can be quantified in a straightforward way, using NO as a probe. This spectroscopic correlation provides a quantitative measure of the thiolate's "push" effect, which is important in O2-activation (Compound I formation) in Cyt P450s in general.

Infrared cameras overestimate skin temperature during rewarming from cold exposure.

OBJECTIVE: The primary aim of this study was to assess the accuracy of an infrared camera and that of a skin thermistor, both commercially available. The study aimed to assess the agreement over a wide range of skin temperatures following cold exposure. METHODS: Fifty-two males placed their right hand in a thin plastic bag and immersed it in 8 °C water for 30 min whilst seated in an air temperature of 30 °C. Following hand immersion, participants removed the bag and rested their hand at heart level for 10 min. Index finger skin temperature (Tsk) was measured with a thermistor, affixed to the finger pad, and an infrared camera measured 1 cm distally to the thermistor. Agreement between the infrared camera and thermistor was assessed by mean difference (infrared camera minus thermistor) and 95% limits of agreement analysis, accounting for the repeated measures over time. The clinically significant threshold for Tsk differences was set at ±0.5 °C and limits of agreement ±1 °C. RESULTS: As an average across all time points, the infrared camera recorded Tsk 1.80 (SD 1.16) °C warmer than the thermistor, with 95% limits of agreement ranging from -0.46 °C to 4.07 °C. CONCLUSION: Collectively, the results show the infrared camera overestimated Tsk at every time point following local cooling. Further, measurement of finger Tsk from the infrared camera consistently fell outside the acceptable level of agreement (i.e. mean difference exceeding ±0.5 °C). Considering these results, infrared cameras may overestimate peripheral Tsk following cold exposure and clinicians and practitioners should, therefore, adjust their risk/withdrawal criteria accordingly.

The Thiolate Trans Effect in Heme {FeNO}6 Complexes and Beyond: Insight into the Nature of the Push Effect.

Cyt P450 nitric oxide (NO) reductase (P450nor) is an important enzyme in fungal denitrification, responsible for the large-scale production of the greenhouse gas N2O. In the first step of catalysis, the ferric heme-thiolate active site of P450nor binds NO to produce a ferric heme-nitrosyl or {FeNO}6 intermediate (in the Enemark-Feltham notation). In this paper, we present the low-temperature preparation of six new heme-thiolate {FeNO}6 model complexes, [Fe(TPP)(SPh*)(NO)], using a unique series of electron-poor thiophenolates (SPh*-), and their detailed spectroscopic characterization. Our data show experimentally, for the first time, that a direct correlation exists between the thiolate donor strength and the Fe-NO and N-O bond strengths, evident from the corresponding stretching frequencies. This is due to a σ-trans effect of the thiolate ligand, which manifests itself in the population of an Fe-N-O σ-antibonding (σ*) orbital. Via control of the thiolate donor strength (using hydrogen bonds), nature is therefore able to exactly control the degree of activation of the FeNO unit in P450nor. Vice versa, NO can be used as a sensitive probe to quantify the donor strength of a thiolate ligand in a model system or protein, by simply measuring the Fe-NO and N-O frequencies of the ferric NO adduct and then projecting those data onto the correlation plot established here. Finally, we are able to show that the σ-trans effect of the thiolate is the electronic origin of the "push" effect, which is proposed to mediate O-O bond cleavage and Compound I formation in Cyt P450 monooxygenase catalysis.

Electron Paramagnetic Resonance Spectroscopy as a Probe of Hydrogen Bonding in Heme-Thiolate Proteins.

Despite utilizing a common cofactor binding motif, hemoproteins bearing a cysteine-derived thiolate ligand (heme-thiolate proteins) are involved in a diverse array of biological processes ranging from drug metabolism to transcriptional regulation. Though the origin of heme-thiolate functional divergence is not well understood, growing evidence suggests that the hydrogen bonding (H-bonding) environment surrounding the Fe-coordinating thiolate influences protein function. Outside of X-ray crystallography, few methods exist to characterize these critical H-bonding interactions. Electron paramagnetic resonance (EPR) spectra of heme-thiolate proteins bearing a six-coordinate, Fe(III) heme exhibit uniquely narrow low-spin (S = 1/2), rhombic signals, which are sensitive to changes in the heme-thiolate H-bonding environment. To establish a well-defined relationship between the magnitude of g-value dispersion in this unique EPR signal and the strength of the heme-thiolate H-bonding environment, we synthesized and characterized of a series of six-coordinate, aryl-thiolate-ligated Fe(III) porphyrin complexes bearing a tunable intramolecular H-bond. Spectroscopic investigation of these complexes revealed a direct correlation between H-bond strength and g-value dispersion in the rhombic EPR signal. Using density functional theory (DFT), we elucidated the electronic origins of the narrow, rhombic EPR signal in heme-thiolates, which arises from an Fe-S pπ-dπ bonding interaction. Computational analysis of the intramolecularly H-bonded heme-thiolate models revealed that H-bond donation to the coordinating thiolate reduces thiolate donor strength and weakens this Fe-S interaction, giving rise to larger g-value dispersion. By defining the relationship between heme-thiolate electronic structure and rhombic EPR signal, it is possible to compare thiolate donor strengths among heme-thiolate proteins through analysis of low-spin, Fe(III) EPR spectra. Thus, this study establishes EPR spectroscopy as a valuable tool for exploring how second coordination sphere effects influence heme-thiolate protein function.

Indices of physiological strain for firefighters of the Australian Defence Forces.

High levels of exertion and physiological strain are the leading cause of fireground injuries. The Physiological Strain Index (PSI) provides a rating of strain based on body core temperature and heart rate; however, it may underestimate the strain of workers in protective clothing as skin temperature may be elevated. This study aimed to examine the relationship between the PSI and an Adaptive Physiological Strain Index (aPSI) that incorporates skin temperature, among firefighters wearing protective clothing. Nine male firefighters of the Australian Defence Force volunteered to participate. Participants conducted scenario-based activities while wearing turnout gear and breathing apparatus. Working in teams of four, participants would respond to a situation around and within a small building with several rooms that could be filled with smoke, however, no live fire was present. Heart rate, gastrointestinal temperature, and skin temperature were monitored throughout work and rehabilitation. Physiological strain was estimated via the PSI and aPSI. Absolute peak PSI and aPSI ratings were significantly different during work (PSI: 7.3 ± 1.6; aPSI 8.2 ± 2.0; p < 0.001). The aPSI produced higher ratings of physiological strain, >0.5 above PSI, progressively from a moderate level of strain (>6). The aPSI may provide a more accurate indication of a level of "maximal strain" for encapsulated workers than the original PSI, coincident with the occupational limits for body core temperature of 38.0 °C for general occupational groups, or 38.5 °C for selected and acclimatised personnel.

Using an Unmanned Aircraft System (Drone) to Conduct a Complex High Altitude Search and Rescue Operation: A Case Study.

Unmanned aircraft systems, also known as unmanned aerial vehicles or drones, are becoming increasingly common consumer products; their potential applications to search and rescue operations are becoming ever more apparent. A consumer drone was used to locate a mountaineer after he and his climbing partner were separated while summiting Broad Peak in the Karakoram Mountains of northeastern Pakistan, the world's 12th highest summit. The use of a commercial drone in the search for the missing climber allowed for a quick rescue mission, eliminating the need for a fully mobilized rescue party while significantly reducing the risk to the climbers charged with rescuing him. Without the drone, the rescue party would have faced immense challenges, including a vast search area and altitudes near the limits of human physiologic function. With real-time imagery and global positioning system capabilities, drones may become an invaluable tool in search and rescue operations, helping to reduce response time and maintain the safety of responders at high altitude and in many other types of difficult terrain.

Portable Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Cardiopulmonary Bypass Surgery.

A new portable gas phase nitric oxide (NO) generator is described for potential applications in inhaled NO (INO) therapy and during cardiopulmonary bypass (CPB) surgery. In this system, NO is produced at the surface of a large-area mesh working electrode by electrochemical reduction of nitrite ions in the presence of a soluble copper(II)-ligand electron transfer mediator complex. The NO generated is then transported into gas phase by either direct purging with nitrogen/air or via circulating the electrolyte/nitrite solution through a gas extraction silicone fiber-based membrane-dialyzer assembly. Gas phase NO concentrations can be tuned in the range of 5-1000 ppm (parts per million by volume for gaseous species), in proportion to a constant cathodic current applied between the working and counter electrodes. This new NO generation process has the advantages of rapid production times (5 min to steady-state), high Faraday NO production efficiency (ca. 93%), excellent stability, and very low cost when using air as the carrier gas for NO (in the membrane dialyzer configuration), enabling the development of potentially portable INO devices. In this initial work, the new system is examined for the effectiveness of gaseous NO to reduce the systemic inflammatory response (SIR) during CPB, where 500 ppm of NO added to the sweep gas of the oxygenator or to the cardiotomy suction air in a CPB system is shown to prevent activation of white blood cells (granulocytes and monocytes) during extracorporeal circulation with cardiotomy suction conducted with five pigs.

Heme-nitrosyls: electronic structure implications for function in biology.

The question of why mammalian systems use nitric oxide (NO), a potentially hazardous and toxic diatomic, as a signaling molecule to mediate important functions such as vasodilation (blood pressure control) and nerve signal transduction initially perplexed researchers when this discovery was made in the 1980s. Through extensive research over the past two decades, it is now well rationalized why NO is used in vivo for these signaling functions, and that heme proteins play a dominant role in NO signaling in mammals. Key insight into the properties of heme-nitrosyl complexes that make heme proteins so well poised to take full advantage of the unique properties of NO has come from in-depth structural, spectroscopic, and theoretical studies on ferrous and ferric heme-nitrosyls. This Account highlights recent findings that have led to greater understanding of the electronic structures of heme-nitrosyls, and the contributions that model complex studies have made to elucidate Fe-NO bonding are highlighted. These results are then discussed in the context of the biological functions of heme-nitrosyls, in particular in soluble guanylate cyclase (sGC; NO signaling), nitrophorins (NO transport), and NO-producing enzymes. Central to this Account is the thermodynamic σ-trans effect of NO, and how this relates to the activation of the universal mammalian NO sensor sGC, which uses a ferrous heme as the high affinity "NO detection unit". It is shown via detailed spectroscopic and computational studies that the strong and very covalent Fe(II)-NO σ-bond is at the heart of the strong thermodynamic σ-trans effect of NO, which greatly weakens the proximal Fe-NHis (or Fe-SCys) bond in six-coordinate ferrous heme-nitrosyls. In sGC, this causes the dissociation of the proximally bound histidine ligand upon NO binding to the ferrous heme, inducing a significant conformational change that activates the sGC catalytic domain for the production of cGMP. This, in turn, leads to vasodilation and nerve signal transduction. Studies on ferrous heme-nitrosyl model complexes have allowed for a quantification of this thermodynamic σ-trans effect of NO, through the use of high-resolution crystal structures, binding constant studies, single-crystal vibrational spectroscopy and density functional theory (DFT) calculations. These studies have further identified the singly occupied molecular orbital (SOMO) of the NO complexes as the key MO that mediates the thermodynamic σ-trans effect of NO. In comparison to ferrous heme-nitrosyls, ferric heme-nitrosyls display thermodynamically much weaker Fe-NO bonds (from NO binding constants), but at the same time much stronger Fe-NO bonds in their ground states (from vibrational spectroscopy). Using spectroscopic investigations coupled to DFT calculations, this apparent contradiction has been rationalized with the involvement of at least three different electronic states in the binding/dissociation of NO to/from ferric hemes. This is of key significance for the release of NO from NO-producing enzymes like NOS, and further forms the basis for ferric hemes to serve as NO transporters in biological systems.

Tactical combat movements: inter-individual variation in performance due to the effects of load carriage.

An examination into the effects of carried military equipment on the performance of two tactical combat movement simulations was conducted. Nineteen Airfield Defence Guards performed a break contact (five 30-m sprints) and a fire and movement simulation (16 6-m bounds) in five load conditions (10-30 kg). Heavier loads significantly increased movement duration on the break contact (0.8%/kg load) and fire and movement (1.1%/kg). Performance deterioration was observed from the beginning to the end of the series of movements (bounds or sprints) with deterioration becoming significantly greater in heavier load conditions. Inter-individual variation between slower and faster participants showed a range in load effects; 0.6, 0.8%/kg for fast and 1.0, 1.4%/kg for slow (break contact, fire and movement, respectively). Velocity profiles revealed that the initial acceleration and peak velocity were the primary determinants of performance. As the duration of these tactical combat movements reflects periods of heightened vulnerability, these findings highlight important implications for commanders. Practitioner Summary: Increasing amounts of carried military equipment impairs the performance of tactical combat movements. Examination of inter-individual variation in velocity profiles identified that the initial acceleration and the peak velocity achieved during sprints and bounds are key determinants of overall performance.

Effects of Military Load Carriage on Susceptibility to Enemy Fire During Tactical Combat Movements.

Current military operations require soldiers to carry heavy external loads that are widely acknowledged to impair the ability to move tactically on the battlefield. However, to date, the effect of load on susceptibility to enemy fire (the probability of being hit) has not been examined. Nineteen soldiers completed a break contact simulation (five 30-m sprints commencing every 44 seconds) and a fire and movement simulation (sixteen 6-m bounds commencing every 20 seconds) in each of the 5 load conditions (ranging from 9.8 to 30.1 kg). For each simulation, the impact of load on exposure time and peak movement velocity was examined. In addition, the 6 fastest and 6 slowest soldiers (determined by exposure time in the heaviest condition) were parsed into subgroups to examine interindividual differences in response to load. Susceptibility for the 2 subgroups was modeled using exposure time for the 2 simulations and the assumed reaction time, shooting cadence, and shooting accuracy of the enemy. Susceptibility increased as a function of load for both the break contact and fire and movement simulations and became more pronounced when the participant population was parsed into fast and slow groups. When the impact of personal protection systems was isolated and analyzed, it was found that not only were the slower participants more vulnerable (as a result of not wearing the personal protection system) but also more susceptible than the faster participants who carried 11.2 kg more load. Large interindividual differences in response to external load have meaningful consequences for battlefield susceptibility, and it is therefore critical that personnel are afforded tailored training such that they maximize their proficiency in the execution of tactical combat movements.

1958-2014: after 56 years of research, cytochrome p450 reactivity is finally explained.

Nature's wisdom in enzyme design: Compounds I and II in the catalytic cycle of the Cytochrome P450 enzymes have been trapped and characterized recently. This work has provided further insight into the electronic structure and reactivity of these crucial intermediates, and key questions regarding the mechanism of these enzymes have finally been answered.

A Systematic Review of Post-Work Core Temperature Cooling Rates Conferred by Passive Rest.

Physical work increases energy expenditure, requiring a considerable elevation of metabolic rate, which causes body heat production that can cause heat stress, heat strain, and hyperthermia in the absence of adequate cooling. Given that passive rest is often used for cooling, a systematic search of literature databases was conducted to identify studies that reported post-work core temperature cooling rates conferred by passive rest, across a range of environmental conditions. Data regarding cooling rates and environmental conditions were extracted, and the validity of key measures was assessed for each study. Forty-four eligible studies were included, providing 50 datasets. Eight datasets indicated a stable or rising core temperature in participants (range 0.000 to +0.028 °C min-1), and forty-two datasets reported reducing core temperature (-0.002 to -0.070 °C min-1) during passive rest, across a range of Wet-Bulb Globe Temperatures (WBGT). For 13 datasets where occupational or similarly insulative clothing was worn, passive rest resulted in a mean core temperature decrease of -0.004 °C min-1 (-0.032 to +0.013 °C min-1). These findings indicate passive rest does not reverse the elevated core temperatures of heat-exposed workers in a timely manner. Climate projections of higher WBGT are anticipated to further marginalise the passive rest cooling rates of heat-exposed workers, particularly when undertaken in occupational attire.