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The hormonal and cardiovascular responses to atropine and low-intensity exercise were examined in 7 young men. Subjects completed 3 trials in a single blind crossover design. During the first trial (T1), subjects received 2.0 mg of atropine intramuscularly at rest. Subsequently in trial 2 (T2), subjects received a saline placebo before 90 minutes of intermittent exercise, and during trial 3 (T3), they received atropine before 90 min of intermittent exercise [3 x (25-minute cycle/5-minute rest) @ 40% VO2 peak]. Venous blood samples and physiological data were collected before, during, and post exercise. Growth hormone (GH) was significantly increased in T2 but unchanged in T1 and T3. Cortisol (CORT) was unchanged in T1 and T2, but in T3 significantly increased (p <0.05) from 45 to 90 minutes compared to T2. Plasma luteinizing hormone (LH) was unaffected in all trials. Plasma prolactin (PRO) significantly increased in T3 from 45 to 90 minutes in comparison to T2. Norepinephrine (NE) was unaffected in T1, but significantly increased in both T2 and T3 (5 to 90 minutes). NE in T3 was also significantly higher compared to T2 (30 to 90 minutes). The heart rate (HR) and rate pressure product (RPP) significantly increased in all trials (15 to 90 minutes) and T3 was significantly elevated in comparison to T2. The administration of atropine before 90 minutes of low-intensity exercise significantly increased cortisol, prolactin, and norepinephrine, decreased growth hormone, and significantly increased cardiovascular stress. [ABSTRACT FROM AUTHOR]

Background: Tamping explosive charges used by breachers is an increasingly common technique. The ability to increase the directional effectiveness of the charge used, combined with the potential to reduce experienced overpressure on breachers, makes tamping a desirable tool not only from an efficacy standpoint for breachers but also from a safety standpoint for operational personnel. The long-term consequences of blast exposure are an open question and may be associated with temporary performance deficits and negative health symptomatology., Purpose: This work evaluates breaches of varying charge weight, material breached, and tamping device used to determine the value of tamping during various scenarios by measuring actual breaches conducted during military and law enforcement training for efficacy and blast overpressure on Operators., Methods: Three data collections across 18 charges of various construction were evaluated with blast overpressure sensors at various distances and locations where breachers would be located, to assess explosive forces on human personnel engaged in breaching activities., Results and Conclusions: Findings indicate that water tamping in general is a benefit on moderate and heavy charges but offers less benefit at a low charge with regard to mitigating blast overpressure on breachers. Reduced overpressure allows Operators to stage closer to explosives and lowers the potential for compromised reaction time. It also reduces the likelihood of negative consequences that can result from excessive overpressure exposure and allow Operators to "do more with less" in complex environments, where resource access may be limited by logistic or other limitations. However, tamping in all instances improved blast efficacy in creating successful breaches. Future studies are planned to investigate tamping mediums beyond water and environment changes, whether tamping can be used to mitigate acoustic insult, and other explosive types., (2022.)

Sampling the live brain is difficult and dangerous, and withdrawing cerebrospinal fluid is uncomfortable and frightening to the subject, so new sources of real-time analysis are constantly sought. Cell-free DNA (cfDNA) derived from glia and neurons offers the potential for wide-ranging neurological disease diagnosis and monitoring. However, new laboratory and bioinformatic strategies are needed. DNA methylation patterns on individual cfDNA fragments can be used to ascribe their cell-of-origin. Here we describe bisulfite sequencing assays and bioinformatic processing methods to identify cfDNA derived from glia and neurons. In proof-of-concept experiments, we describe the presence of both glia- and neuron-cfDNA in the blood plasma of human subjects following mild trauma. This detection of glia- and neuron-cfDNA represents a significant step forward in the translation of liquid biopsies for neurological diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chatterton, Mendelev, Chen, Carr, Kamimori, Ge, Dwork and Haghighi.)

Importance: There is a scientific and operational need to define objective measures of exposure to low-level overpressure (LLOP) and concussion-like symptoms among persons with specialized occupations., Objective: To evaluate serum levels of neurotrauma biomarkers and their association with concussion-like symptoms reported by LLOP-exposed military and law enforcement personnel who are outwardly healthy and cleared to perform duties., Design, Setting, and Participants: This retrospective cohort study, conducted from January 23, 2017, to October 21, 2019, used serum samples and survey data collected from healthy, male, active-duty military and law enforcement personnel assigned to operational training at 4 US Department of Defense and civilian law enforcement training sites. Personnel aged 18 years or older with prior LLOP exposure but no diagnosed traumatic brain injury or with acute blast exposure during sampling participated in the study. Serum samples from 30 control individuals were obtained from a commercial vendor., Main Outcomes and Measures: Serum levels of glial fibrillary acidic protein, ubiquitin carboxyl hydrolase (UCH)-L1, neurofilament light chain, tau, amyloid β (Aβ)-40, and Aβ-42 from a random sample (30 participants) of the LLOP-exposed cohort were compared with those of 30 age-matched controls. Associations between biomarker levels and self-reported symptoms or operational demographics in the remainder of the study cohort (76 participants) were assessed using generalized linear modeling or Spearman correlations with age as a covariate., Results: Among the 30 randomly sampled participants (mean [SD] age, 32 [7.75] years), serum levels of UCH-L1 (mean difference, 4.92; 95% CI, 0.71-9.14), tau (mean difference, 0.16; 95% CI, -0.06 to 0.39), Aβ-40 (mean difference, 138.44; 95% CI, 116.32-160.56), and Aβ-42 (mean difference, 4.97; 95% CI, 4.10-5.83) were elevated compared with those in controls. Among the remaining cohort of 76 participants (mean [SD] age, 34 [7.43] years), ear ringing was reported by 44 (58%) and memory or sleep problems were reported by 24 (32%) and 20 (26%), respectively. A total of 26 participants (34%) reported prior concussion. Amyloid β-42 levels were associated with ear ringing (F1,72 = 7.40; P = .008) and memory problems (F1,72 = 9.20; P = .003)., Conclusions and Relevance: The findings suggest that long-term LLOP exposure acquired during occupational training may be associated with serum levels of neurotrauma biomarkers. Assessment of biomarkers and concussion-like symptoms among personnel considered healthy at the time of sampling may be useful for military occupational medicine risk management.

Caffeine is widely used to promote alertness and cognitive performance under challenging conditions, such as sleep loss. Non-digestive modes of delivery typically reduce variability of its effect. In a placebo-controlled, 50-h total sleep deprivation (TSD) protocol we administered four 200 mg doses of caffeine-infused chewing-gum during night-time circadian trough and monitored participants' drowsiness during task performance with infra-red oculography. In addition to the expected reduction of sleepiness, caffeine was found to disrupt its degrading impact on performance errors in tasks ranging from standard cognitive tests to simulated driving. Real-time drowsiness data showed that caffeine produced only a modest reduction in sleepiness (compared to our placebo group) but substantial performance gains in vigilance and procedural decisions, that were largely independent of the actual alertness dynamics achieved. The magnitude of this disrupting effect was greater for more complex cognitive tasks.

Introduction: During training and combat operations, military personnel may be exposed to repetitive low-level blast while using explosives to gain entry or by firing heavy weapon systems such as recoilless weapons and high-caliber sniper rifles. This repeated exposure, even within allowable limits, has been associated with cognitive deficits similar to that of accidental and sports concussion such as delayed verbal memory, visual-spatial memory, and executive function. This article presents a novel framework for accurate calculation of the human body blast exposure in military heavy weapon training scenarios using data from the free-field and warfighter wearable pressure sensors., Materials and Methods: The CoBi human body model generator tools were used to reconstruct multiple training scenes with different weapon systems. The CoBi Blast tools were used to develop the weapon signature and estimate blast overpressure exposure. The authors have used data from the free-field and wearable pressure sensors to evaluate the framework., Results: Carl-Gustav and 0.50 caliber sniper training scenarios were used to demonstrate and validate the developed framework. These simulations can calculate spatially and temporally resolved blast loads on the whole human body and on specific organs vulnerable to blast loads, such as head, face, and lungs., Conclusions: This framework has numerous advantages including easier model setup and shorter simulation times. The framework is an important step towards developing an advanced field-applicable technology to monitor low-level blast exposure during heavy weapon military training and combat scenarios., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study compared the response of the wearable sensors tested against the industry-standard pressure transducers at blast overpressure (BOP) levels typically experienced in training. We systematically evaluated the effects of the sensor orientation with respect to the direction of the incident shock wave and demonstrated how the averaging methods affect the reported pressure values. The evaluated methods included averaging peak overpressure and impulse of all four sensors mounted on a helmet, taking the average of the three sensors, or isolating the incident pressure equivalent using two sensors. The experimental procedures were conducted in controlled laboratory conditions using the shock tube, and some of the findings were verified in field conditions with live fire charges during explosive breaching training. We used four different orientations (0°, 90°, 180°, and 270°) of the headform retrofitted with commonly fielded helmets (ACH, ECH, Ops-Core) with four B3 Blast Gauge sensors. We determined that averaging the peak overpressure values overestimates the actual dosage experienced by operators, which is caused by the reflected pressure contribution. This conclusion is valid despite the identified limitation of the B3 gauges that consistently underreport the peak reflected overpressure, compared to the industry-standard sensors. We also noted consistent overestimation of the impulse. These findings demonstrate that extreme caution should be exercised when interpreting occupational blast exposure results without knowing the orientation of the sensors. Pure numerical values without the geometrical, training-regime specific information such as the position of the sensors, the distance and orientation of the trainee to the source of the blast wave, and weapon system used will inevitably lead to erroneous estimation of the individual and cumulative blast overpressure (BOP) dosages. Considering that the 4 psi (~28 kPa) incident BOP is currently accepted as the threshold exposure safety value, a misinterpretation of exposure level may lead to an inaccurate estimation of BOP at the minimum standoff distance (MSD), or exclusion criteria., Competing Interests: The authors have declared that no competing interests exist.

Background: Overpressure (OP) is an increase in air pressure above normal atmospheric levels. Military personnel are repeatedly exposed to low levels of OP caused by various weapon systems. Repeated OP may increase risk of neurological disease or psychological disorder diagnoses. A means to detect early phase effects that may be relevant to brain trauma remain elusive. Therefore, development of quantitative and objective OP-mediated effects during acute timeframes would vastly augment point-of-care or field-based decisions. This pilot study evaluated the amplitude of traumatic brain injury (TBI)-associated biomarkers in serum as a consequence of repeated OP exposure from .50-caliber rifle use over training multiple days. Objective: To determine the acute temporal profile of TBI-associated serum biomarkers and their relationship with neurocognitive decrements or self-reported symptoms among participants exposed to low-level, repeated OP from weapons used in a training environment. Methods: Study participants were enrolled in .50-caliber sniper rifle training and exposed to mild OP (peak pressure 3.8-4.5 psi, impulse 19.27-42.22 psi-ms per day) for three consecutive days (D1-D3). Defense automated neurobehavioral assessment (DANA) neurocognitive testing, symptom reporting, and blood collection were conducted 2-3 h before (pre-) and again 0.45-3 h after (post-) OP exposure. The TBI-associated serum biomarkers, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (Nf-L), tau, and amyloid beta peptides (Aβ-40 and Aβ-42) were measured using digital ELISAs. Results: Serum GFAP decreased on D1 and D3 but not D2 after OP exposure. Nf-L was suppressed on D3 alone. Aβ-40 was elevated on D2 alone while Aβ-42 was elevated each day after OP exposure. Suppression of GFAP and elevation of Aβ-42 correlated to OP-mediated impulse levels measured on D3. Conclusions: Acute measurement of Aβ-peptides may have utility as biomarkers of subconcussive OP caused by rifle fire. Fluctuation of GFAP, Nf-L, and particularly Aβ peptide levels may have utility as acute, systemic responders of subconcussive OP exposure caused by rifle fire even in the absence of extreme operational deficits or clinically defined concussion., (This work is authored by Bharani Thangavelu, Christina R. LaValle, Michael J. Egnoto, Jeffrey Nemes, Angela M. Boutté, and Gary H. Kamimori on behalf of the U.S. Government and, as regards Thangavelu, LaValle, Egnoto, Nemes, Boutté, Kamimori, and the U.S. Government, is not subject to copyright protection in the United States. Foreign and other copyrights may apply.)

Sleep deprivation (SD) and fatigue have detrimental effects on performance in operational settings. Few studies have investigated the cumulative effects of SD and fatigue on performance under heavy workload demands. Therefore, we investigated the efficacy of multiple repeated doses of caffeine as a countermeasure to SD and fatigue during 77 h total SD (TSD) during the early morning hours. Twenty-three males and females, 18 - 35 years of age, who identified as moderate caffeine consumers completed the Psychomotor Vigilance Task (PVT) 141 times during the experimental test period. Caffeine was administered in a multi-dose paradigm over three nights without sleep. Participants received either caffeine (200 mg) or placebo at the beginning of each 2-h test block from 0100 - 0900 (800 mg total per night). While PVT speed declined for both groups across all 3 nights, the caffeine group consistently out-performed the placebo group. Caffeine maintained attentiveness (1-5 s lapses) on night 1, but this advantage was lost on nights 2 and 3. Caffeine outperformed placebo for responsive lapses (5-9 s lapses) across all three nights, but caffeine performance was still notably worse than at baseline. Prolonged non-responsive lapses (beyond 10 s) were only reduced by caffeine on night 2. Caffeine was more effective than placebo across all nights at sustaining completion speed of a complex motor sequence task and a manual coordination task. Essentially, caffeine is an effective countermeasure for SD, as it mitigates declines in speed and failures to respond, and sustains motor planning and coordination. However, caffeine does not restore normal functioning during SD and cannot be considered as a replacement for sleep., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 The Authors. Published by Elsevier Inc.)

Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military "breachers" were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low versus high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise-related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre- versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥1.5), including UFC1 and YOD1 ubiquitin-related proteins, were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely after blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.

This article provides information regarding the effect of four common high abundant protein (albumin and immunoglobulins (Ig)) depletion strategies upon serum proteomics datasets derived from normal, non-diseased rat or human serum. After tryptic digest, peptides were separated using C 18 reverse phase liquid chromatography-tandem mass spectrometry (rpLC-MS/MS). Peptide spectral matching (PSM) and database searching was conducted using MS Amanda 2.0 and Sequest HT. Peptide and protein false discovery rates (FDR) were set at 0.01%, with at least two peptides assigned per protein. Protein quantitation and the extent of albumin and Ig removal was defined by PSM counts. Venn diagram analysis of the core proteomes, derived from proteins identified by both search engines, was performed using Venny. Ontological characterization and gene set enrichment were performed using WebGestalt. The dataset resulting from each depletion column is provided., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

The complex interfacial condition between the human brain and the skull has been difficult to emulate in a surrogate system. Surrogate head models have typically been built using a homogeneous viscoelastic material to represent the brain, but the effect of different interfacial conditions between the brain and the skull on pressure transduction into the brain during blast has not been studied. In the present work, three interfacial conditions were generated in physical surrogate human head models. The first surrogate consisted of a gel brain separated from the skull by a layer of saline solution similar in thickness to the cerebrospinal fluid (CSF) layer in the human head: the fluid interface head model. The second surrogate head had the entire cranial cavity filled with the gel: the fixed interface head model. The third surrogate head contained a space-filling gel brain wrapped in a thin plastic film: the stick-slip interface head model. The human head surrogates were evaluated in a series of frontal blast tests to characterize the effect of skull-brain interfacial conditions on overpressure propagation into the gel brains. The fixed and the stick-slip interface head models showed nearly equal peak brain overpressures. In contrast, the fluid interface head model had much higher in-brain peak overpressures than the other two models, thus representing the largest transmission of forces into the gel brain. Given that the elevated peak overpressures occurred only in the fluid interface head model, the presence of the saline layer is likely responsible for this increase. This phenomenon is hypothesized to be attributed to the incompressibility of the saline and/or the impedance differences between the materials. The fixed interface head model showed pronounced high frequency energy content relative to the other two models, implying that the fluid and the stick-slip conditions provided better dampening. The cumulative impulse energy entering the three brain models were similar, suggesting that the interface conditions do not affect the total energy transmission over the positive phase duration of a blast event. This study shows that the fidelity of the surrogate human head models would improve with a CSF-emulating liquid layer., (Copyright © 2020 Chen, O'Shaughnessy, Kamimori, Horner, Egnoto and Bagchi.)

We report a case study on a single military member who received moderate blast overpressure (OP) exposure during routine breacher training. We extend previous research on blast exposure during training, which lacked sufficient data to assess symptom profiles and OP exposure. The present work was conducted because a subjective symptom profile similar to that seen in sports concussion has been reported by military personnel exposed to blast. Data collection for this study was carried out under a research protocol approved by the relevant Human Subjects Review Committees on one subject, who received the highest OP exposure during training. The volunteer was a 20-year-old male with no prior history of traumatic brain injury (TBI) or blast exposure. The volunteer was part of a breacher training team that completed a 2-week explosive entry course. The course included 3 classroom days and 9 days of practical training, held in the morning, afternoon, and evening sessions. Blast exposure occurred on five of the nine practical training days, with multiple exposures over the course of each day. Assessments of serum, self-reported symptoms, magnetic resonance imaging, and blast characterization were conducted. Results indicated changes in glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 postblast exposure but did not manifest changes in spectrin-derived breakdown product 150 or magnetic resonance imaging. No additional symptoms were reported by the subject. Objective markers of mild TBI remain elusive, but support for serum biomarkers as an early detection mechanism is promising. Additionally, this case study demonstrated an association between OP and high level of neurotrauma biomarker in an individual., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Addressing the concerns surrounding blast injury for the military community is a pressing matter. Specifically, sub-concussive blast effects, or those blast effects which do not yield a medical diagnosis but can result in symptom reporting and negative self-reported outcomes, are becoming increasingly important. This work evaluates explosive blast overpressure and impulse effects at the sub-concussive level on neurocognitive performance assessed with the Defense Automated Neurobehavioral Assessment (DANA) across seven breacher training courses conducted by the US Military. The results reported here come from 202 healthy, male military volunteer participants. Findings indicate that the neurocognitive task appearing most sensitive to identifying performance change is the DANA Procedural Reaction Time (PRT) subtask which may involve a sufficient level of challenge to reliably detect a small, transient cognitive impairment among a healthy undiagnosed population. The blast characteristic that was consistently associated with performance change was peak overpressure. Overall, this study provides evidence that increasing blast overpressure, defined as peak overpressure experienced in a training day, can lead to transient degradations in neurocognitive performance as seen on the DANA PRT subtask, which may generalize to other capabilities., (Copyright © 2019 LaValle, Carr, Egnoto, Misistia, Salib, Ramos and Kamimori.)

Blast overpressure exposure has been linked to transient, but measurably deteriorated performance and symptomatologies in law enforcement and military personnel. Overlapping sub-concussive symptomatology associated with the very low level blast overpressures (vLLB) but high sound pressure (<3 psi) associated with these exposures has largely been ignored. Notably, the current vLLB or acoustic literature has focused exclusively on auditory defects, and has not addressed the broader concerns of Soldier health and readiness. This work was prompted by reports of symptomatology such as headache, nausea, slowed reaction time, and balance/hearing complications among personnel undergoing frequent exposures to low overpressure accompanied by high acoustic pressures. To more fully address the consequences associated with low overpressure exposures (<3 psi), a pilot proof-of-concept study was implemented, and data was acquired at two sites on the Fort Benning grenade course range. Findings indicated overpressures ranged from 0.14 to 0.42 psi (0.97-2.89 kPa) at range 1 and 0.22-0.30 psi (1.52-2.07 kPa) on range 2 of the grenade course. Corresponding sound-meter data varied from 153.72 to 163.22 dBP. Headache and long think were the most frequently reported symptoms (3/6 instructors), with lightheadedness, ringing of the ears, restlessness, frustration, and irritability also increasing in 2/6 of the instructors post exposure. Long think (prolonged thinking), ringing of the ears, restlessness, and irritability were the most severe symptoms, with the highest reported post exposure value rating a 3 on the 0-4-point scale. We demonstrate that low-level repeated overpressure exposure can result in transient symptomatology that overlaps with sub-concussive like effects.

Repeated exposure to blast overpressure remains a major cause of adverse health for military personnel who, as a consequence, are at a higher risk for neurodegenerative disease and suicide. Acute, early tracking of blast related effects holds the promise of rapid health assessment prior to onset of chronic problems. Current techniques used to determine blast-related effects rely upon reporting of symptomology similar to that of concussion and neurocognitive assessment relevant to operational decrement. Here, we describe the results of a cross sectional study with pared observations. The concentration of multiple TBI-related proteins was tested in serum collected within one hour of blast exposure as a quantitative and minimally invasive strategy to augment assessment of blast-exposure effects that are associated with concussion-like symptomology and reaction time decrements. We determined that median simple reaction time (SRT) was slowed in accordance with serum Nf-L, tau, Aβ-40, and Aβ-42 elevation after overpressure exposure. In contrast, median levels of serum GFAP decreased. Individual, inter-subject analysis revealed positive correlations between changes in Nf-L and GFAP, and in Aβ-40 compared to Aβ-42. The change in Nf-L was negatively associated with tau, Aβ-40, and Aβ-42. Participants reported experiencing headaches, dizziness and taking longer to think. Dizziness was associated with reaction time decrements, GFAP or NfL suppression, as well as Aβ peptide elevation. UCH-L1 elevation had a weak association with mTBI/concussion history. Multiplexed serum biomarker quantitation, coupled with reaction time assessment and symptomology determined before and after blast exposure, may serve as a platform for tracking adverse effects in the absence of a head wound or diagnosed concussion. We propose further evaluation of serum biomarkers, which are often associated with TBI, in the context of acute operational blast exposures., Competing Interests: The authors have declared that no competing interests exist.

Self-assessment is the most common method for monitoring performance and safety in the workplace. However, discrepancies between subjective and objective measures have increased interest in physiological assessment of performance. In a double-blind placebo-controlled study, 23 healthy adults were randomly assigned to either a placebo (n = 11; 5 F, 6 M) or caffeine condition (n = 12; 4 F, 8 M) while undergoing 50 h (i.e. two days) of total sleep deprivation. In previous work, higher salivary alpha-amylase (sAA) levels were associated with improved psychomotor vigilance and simulated driving performance in the placebo condition. In this follow-up article, the effects of strategic caffeine administration on the previously reported diurnal profiles of sAA and performance, and the association between sAA and neurobehavioural performance were investigated. Participants were given a 10 h baseline sleep opportunity (monitored via standard polysomnography techniques) prior to undergoing sleep deprivation (total sleep time: placebo = 8.83 ± 0.48 h; caffeine = 9.01 ± 0.48 h). During sleep deprivation, caffeine gum (200 mg) was administered at 01:00 h, 03:00 h, 05:00 h, and 07:00 h to participants in the caffeine condition (n = 12). This strategic administration of caffeine gum (200 mg) has been shown to be effective at maintaining cognitive performance during extended wakefulness. Saliva samples were collected, and psychomotor vigilance and simulated driving performance assessed at three-hour intervals throughout wakefulness. Caffeine effects on diurnal variability were compared with previously reported findings in the placebo condition (n = 11). The impact of caffeine on the circadian profile of sAA coincided with changes in neurobehavioural performance. Higher sAA levels were associated with improved performance on the psychomotor vigilance test during the first 24 h of wakefulness in the caffeine condition. However, only the association between sAA and response speed (i.e. reciprocal-transform of mean reaction time) was consistent across both days of sleep deprivation. The association between sAA and driving performance was not consistent across both days of sleep deprivation. Results show that the relationship between sAA and reciprocal-transform of mean reaction time on the psychomotor vigilance test persisted in the presence of caffeine, however the association was relatively weaker as compared with the placebo condition., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Caffeine is known for its capacity to mitigate performance decrements. The metabolic side-effects are less well understood. This study examined the impact of cumulative caffeine doses on glucose metabolism, self-reported hunger and mood state during 50 hr of wakefulness. In a double-blind laboratory study, participants were assigned to caffeine (n = 9, 6M, age 21.3 ± 2.1 years; body mass index 21.9 ± 1.6 kg/m 2 ) or placebo conditions (n = 8, 4M, age 23.0 ± 2.8 years; body mass index 21.8 ± 1.6 kg/m 2 ). Following a baseline sleep (22:00 hours-08:00 hours), participants commenced 50 hr of sleep deprivation. Meal timing and composition were controlled throughout the study. Caffeine (200 mg) or placebo gum was chewed for 5 min at 01:00 hours, 03:00 hours, 05:00 hours and 07:00 hours during each night of sleep deprivation. Continual glucose monitors captured interstitial glucose 2 hr post-breakfast, at 5-min intervals. Hunger and mood state were assessed at 10:00 hours, 16:30 hours, 22:30 hours and 04:30 hours. Caffeine did not affect glucose area under the curve (p = 0.680); however, glucose response to breakfast significantly increased after 2 nights of extended wakefulness compared with baseline (p = 0.001). There was a significant main effect of day, with increased tiredness (p < 0.001), mental exhaustion (p < 0.001), irritability (p = 0.002) and stress (p < 0.001) on the second day of extended wake compared with day 1. Caffeine attenuated the rise in tiredness (p < 0.001), mental exhaustion (p = 0.044) and irritability (p = 0.018) on day 1 but not day 2. Self-reported hunger was not affected by sleep deprivation or caffeine. These data confirm the effectiveness of caffeine in improving performance under conditions of sleep deprivation by reducing feelings of tiredness, mental exhaustion and irritability without exacerbating glucose metabolism and feelings of hunger., (© 2018 European Sleep Research Society.)

"Breachers" (dynamic entry personnel) are routinely exposed to low-level blast overpressure during training and occupational duties. Data were collected from 22 military breachers (mean 29.7 yr) over a 5-yr period to characterize the longitudinal effects of repeated low-level blast overpressure exposure. None of the participants reported a diagnosed concussion during the study period. Blood-based biomarker concentrations (n = 22) showed either no significant change or a significant decrease over time. Neurocognitive performance (n = 20) and symptom reporting (n = 22) did not change over time. Neuroimaging analyses resulted in no significant differences for within-subject (baseline vs follow-up, n = 8) and between-subject (naïve, n = 5 vs experienced, n = 8) comparisons. Changes to training doctrine mid-study reduced blast exposure (< 4 psi) and may have mitigated any measurable effects associated with long-term, low-level blast exposure. The results suggest that the first 5 yr of a breaching career in healthy, young individuals is unlikely to result in measurable effects when overpressure exposure is maintained within the 4 psi safe limit. The lack of any significant changes in these operators suggests that either no identifiable injuries occurred and/or measurement tools may not be sensitive enough to identify any negative subconcussive effects.

Background: Increasingly, military and law enforcement are using .50-caliber rifles for conflict resolution involving barricades, armor, vehicles, and situations that require increased kinetic energy. Consequences to the shooter resulting from the blast produced while firing these rifles remain unknown. We measured blast overpressure (OP) and impulse across various positions, environments, and weapon configurations to evaluate blast exposures to shooters., Methods: Two separate, multiday, .50-caliber rifle training courses were evaluated to understand the blast exposure profile received from various tactical training scenarios, such as different firing positions (e.g., standing, prone, seated, kneeling) and locations (e.g., inside and atop vehicles, inside buildings, on hard/soft surfaces) across a variety of .50-caliber rifles with various barrel lengths, muzzle devices, and ammunition. Blackbox Biometrics, Generation 6, gauges were placed on operators to measure incident blast exposure. A total of 444 rounds fired from various .50-caliber rifles were evaluated to determine what OP was received by 32 different shooters., Results: Our findings indicate OPs >4 psi are common and that muzzle devices are critical to blast exposure. Shooting positions closer to the ground experienced higher OP and impulse than did other positions. Suppressors mitigated blast effects well., Conclusion: When resources and operational parameters allow, suppressors are recommended, as are positions that move the shooter farther from reflective surfaces (standing preferred) to effectively reduce blast exposure. These shooter positions may require the use of supplemental rifle rests/tripods to provide sufficiently stable firing platforms from the standing position., (2018.)

During sleep deprivation, neurobehavioral functions requiring sustained levels of attention and alertness are significantly impaired. Discrepancies between subjective measures of sleepiness and objective performance during sustained operations have led to interest in physiological monitoring of operator performance. Alertness, vigilance, and arousal are modulated by the wake-promoting actions of the central noradrenergic system. Salivary alpha-amylase (sAA) has been proposed as a sensitive peripheral measure of noradrenergic activity, but limited research has investigated the relationship between sAA and performance. In a laboratory-controlled environment, we investigated the relationship between sAA levels, subjective sleepiness, and performance during two days (50h) of total sleep deprivation. Beginning at 09:00, twelve healthy participants (5 females) aged 22.5±2.5years (mean±SD) provided saliva samples, recorded ratings of subjective sleepiness, completed a brief 3-min psychomotor vigilance task (PVT-B) and performed a 40-min simulated driving task, at regular 3h intervals during wakefulness. Ratings of subjective sleepiness exhibited a constant linear increase (p<0.001) during sleep deprivation. In contrast, sAA levels showed a marked diurnal profile, with levels increasing during the day (p<0.001) and steadily declining in the evening and early-morning (p<0.001). PVT-B (mean reaction time and mean slowest 10% reaction time) and simulated driving performance (speed deviation and lane deviation) also exhibited diurnal profiles across the two days of sleep deprivation. Performance peaked in the afternoon (p<0.001) and then steadily worsened as wakefulness continued into the evening and early-morning (p<0.001). Further analysis revealed that higher sAA levels in the hour preceding each performance assessment were associated with better PVT-B and driving performance (p<0.001). These findings suggest that sAA measures may be suitable indicators of performance deficits during sustained wakefulness and highlight the potential for sAA to be considered for physiological monitoring of performance. In operational environments sAA levels, as part of a panel of physiological measures, may be useful for assessing fitness-for-duty prior to safety being compromised or when performance deficits are unknown., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The combination of mental and physical challenges can elicit exacerbated cardiorespiratory (CR) and catecholamine responses above that of a single challenge alone., Purpose: This study examined the effects of a combination of acute mental challenges and physical stress on cardiorespiratory and catecholamine responses., Method: Eight below-average fitness (LF VO 2max  = 36.58 ± 3.36 ml -1  kg -1  min -1 ) and eight above-average fitness (HF VO 2max  = 51.18 ± 2.09 ml -1  kg -1  min -1 ) participants completed an exercise-alone condition (EAC) session consisting of moderate-intensity cycling at 60% VO 2max for 37 min, and a dual-challenge condition (DCC) that included concurrent participation in mental challenges while cycling., Result: The DCC resulted in increases in perceived workload, CR, epinephrine, and norepinephrine responses overall. HF participants had greater absolute CR and catecholamine responses compared to LF participants and quicker HR recovery after the dual challenge., Conclusion: These findings demonstrate that cardiorespiratory fitness does impact the effect of concurrent stressors on CR and catecholamine responses.

Study Objectives: Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies., Methods: We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory- and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg)., Results: The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%., Conclusions: The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance., (© 2016 Associated Professional Sleep Societies, LLC.)

The current study investigated the effects of repeated caffeine administration on performance and subjective reports of sleepiness and fatigue during 50h extended wakefulness. Twenty-four, non-smokers aged 22.5±2.9y (mean±SD) remained awake for two nights (50h) in a controlled laboratory environment. During this period, 200mg of caffeine or placebo gum was administered at 01:00, 03:00, 05:00 and 07:00 on both nights (total of 800mg/night). Neurobehavioral performance and subjective reports were assessed throughout the wake period. Caffeine improved performance compared to placebo, but did not affect overall ratings of subjective sleepiness and fatigue. Performance and sleepiness worsened with increasing time awake for both conditions. However, caffeine slowed performance impairments such that after 50h of wakefulness performance was better following caffeine administration compared to placebo. Caffeine also slowed the increase in subjective sleepiness and performance ratings, but only during the first night of wakefulness. After two nights of sleep deprivation, there was no difference in sleepiness ratings between the two conditions. These results demonstrate that strategic administration of caffeine effectively mitigates performance impairments associated with 50h wakefulness but does not improve overall subjective assessments of sleepiness, fatigue and performance. Results indicate that while performance impairment is alleviated, individuals may continue to report feelings of sleepiness. Individuals who use caffeine as a countermeasure in sustained operations may feel as though caffeine is not effective despite impairments in objective performance being largely mitigated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Rationale: Various occupational groups are required to maintain optimal physical and cognitive function during overnight periods of wakefulness, often with less than optimal sleep. Strategies are required to help mitigate the impairments in cognitive function to help sustain workplace safety and productivity., Objectives: To test the effectiveness of repeated 200 mg doses of caffeine on cognitive function and live-fire marksmanship with soldiers during three successive nights of sustained wakefulness followed by 4-h afternoon sleep periods., Methods: Twenty Special Forces personnel (28.6 ± 4.7 years, 177.6 ± 7.5 cm and 81.2 ± 8.0 kg) were randomly assigned to receive four 200-mg doses of caffeine (n = 10) or placebo (n = 10) during the late evening and early morning hours during three successive days. An afternoon 4-h sleep period followed. The psychomotor (PVT) and field (FVT) vigilance, logical reasoning (LRT) tests and a vigilance monitor assessed cognitive function throughout the study. Live-fire marksmanship requiring friend-foe discrimination was assessed., Results: Caffeine maintained speed on the PVT (p < 0.02), improved detection of events during FVT (p < 0.001), increased number of correct responses to stimuli as assessed by the vigilance monitor (p < 0.001) and increased response speed during the LRT (p < 0.001) throughout the three overnight testing periods. Live-fire marksmanship was not altered by caffeine., Conclusions: A total daily dose of 800 mg caffeine during successive overnight periods of wakefulness is an effective strategy to maintain cognitive function when optimal sleep periods during the day are not available.

Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has some empirical support and was evaluated in this study. We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast effect are needed.

Caffeine is the most widely consumed stimulant to counter sleep-loss effects. While the pharmacokinetics of caffeine in the body is well-understood, its alertness-restoring effects are still not well characterized. In fact, mathematical models capable of predicting the effects of varying doses of caffeine on objective measures of vigilance are not available. In this paper, we describe a phenomenological model of the dose-dependent effects of caffeine on psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used the two-process model of sleep regulation to quantify performance during sleep loss in the absence of caffeine and a dose-dependent multiplier factor derived from the Hill equation to model the effects of single and repeated caffeine doses. We developed and validated the model fits and predictions on PVT lapse (number of reaction times exceeding 500 ms) data from two separate laboratory studies. At the population-average level, the model captured the effects of a range of caffeine doses (50-300 mg), yielding up to a 90% improvement over the two-process model. Individual-specific caffeine models, on average, predicted the effects up to 23% better than population-average caffeine models. The proposed model serves as a useful tool for predicting the dose-dependent effects of caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance., (Published by Elsevier Ltd.)

"Breachers" are a unique military and law enforcement population because they are routinely exposed to low-level blast (LLB) during training and operations. This repeated exposure has been associated with symptoms similar to that of sports concussion. This study examined effects of repeated exposure to LLB during an explosive entry course. Twenty-one members of the New Zealand Defence Force volunteered for this study. Serum samples, neurocognitive performance, and self-reported symptoms were periodically measured before, during, and after a 2-week course. Serum concentrations of three biomarkers, ubiquitin C-terminal hydrolase-L1, αII-spectrin breakdown product, and glial fibrillary acidic protein, were determined with sandwich enzyme-linked immunosorbent assays, and rank scores were derived using the area under the curve (relative to baseline) for each subject. Neurocognitive performance was measured with a computer-based test battery, and symptoms were assessed by paper-based inventory. There was a significant relationship (p<0.05) between composite biomarker and neurocognitive performance and between neurocognitive performance and symptoms. The individuals with the five highest (Top 5) and lowest (Bottom 5) composite biomarker scores were identified and compared using Wilcoxon's rank-sum test. The Top 5 had significantly longer reaction times and lower percent correct on neurocognitive performance and an increase in symptom reporting. The difference between individuals expressing the highest biomarker load during breacher training (Top 5) and those with the lowest biomarker load (Bottom 5) is reflected in neurocognitive performance deficits and self-reported symptoms. This suggests a measureable degree of brain perturbation linked to LLB exposure. Follow-up studies are underway to expand upon these results.

Rationale: While caffeine is widely used as a countermeasure to sleep loss, mathematical models are lacking., Objective: Develop a biomathematical model for the performance-restoring effects of caffeine in sleep-deprived subjects., Methods: We hypothesized that caffeine has a multiplicative effect on performance during sleep loss. Accordingly, we first used a phenomenological two-process model of sleep regulation to estimate performance in the absence of caffeine, and then multiplied a caffeine-effect factor, which relates the pharmacokinetic-pharmacodynamic effects through the Hill equation, to estimate the performance-restoring effects of caffeine., Results: We validated the model on psychomotor vigilance test data from two studies involving 12 subjects each: (1) single caffeine dose of 600mg after 64.5h of wakefulness and (2) repeated doses of 200mg after 20, 22, and 24h of wakefulness. Individualized caffeine models produced overall errors that were 19% and 42% lower than their population-average counterparts for the two studies. Had we not accounted for the effects of caffeine, the individualized model errors would have been 117% and 201% larger, respectively., Conclusions: The presented model captured the performance-enhancing effects of caffeine for most subjects in the single- and repeated-dose studies, suggesting that the proposed multiplicative factor is a feasible solution., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Naps are an effective strategy for maintaining alertness and cognitive performance; however, upon abrupt wakening from naps, sleep inertia (temporary performance degradation) may ensue. In the present study, attenuation of post-nap sleep inertia was attempted by administration of caffeine gum. Using a double-blind, placebo-controlled crossover design, 15 healthy, non-smoking adults were awakened at 1 hr. and again at 6 hr. after lights out (0100 and 0600, respectively) and were immediately administered a gum pellet containing 100 mg of caffeine or placebo. A 5-min. psychomotor vigilance task was administered at 0 min., 6 min., 12 min., and 18 min. post-awakening. At 0100, response speed with caffeine was significantly better at 12 min. and 18 min. post-awakening compared to placebo; at 0600, caffeine's effects were evident at 18 min. post-awakening. Caffeinated gum is a viable means of rapidly attenuating sleep inertia, suggesting that the adenosine receptor system is involved in sleep maintenance.

Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion. The purpose of the current investigation was to examine the effect of low-dose caffeine (CAF) administered in chewing gum at 3 different time points during submaximal cycling exercise to exhaustion. Eight college-aged (26 ± 4 years), physically active (45.5 ± 5.7 ml·kg(-1)·min(-1)) volunteers participated in 4 experimental trials. Two pieces of caffeinated chewing gum (100 mg per piece, total quantity of 200 mg) were administered in a double-blind manner at 1 of 3 time points (-35, -5, and +15 minutes) with placebo at the other 2 points and at all 3 points in the control trial. The participants cycled at 85% of maximal oxygen consumption until volitional fatigue and time to exhaustion (TTE) were recorded in minutes. Venous blood samples were obtained at -40, -10, and immediately postexercise and analyzed for serum-free fatty acid and plasma catecholamine concentrations. Oxygen consumption, respiratory exchange ratio, heart rate, glucose, lactate, ratings of perceived exertion, and perceived leg pain measures were obtained at baseline and every 10 minutes during cycling. The results showed that there were no significant differences between the trials for any of the parameters measured including TTE. These findings suggest that low-dose CAF administered in chewing gum has no effect on TTE during cycling in recreational athletes and is, therefore, not recommended.

The purpose of this study was to examine the effects of a mental challenge on cardiovascular and endocrine [epinephrine (EPI), norepinephrine (NE), and cortisol (CORT)] responses to subsequent low-intensity physical exertion. Twelve males (23.25±0.45 years) completed three sessions, including a graded exercise test on a cycle ergometer and two counter-balanced mental stress trials. In the mental challenge-control condition (MC), participants sat quietly for 20 min following a 20 min mental challenge whereas in the mental challenge-exercise condition (MEC) subjects cycled at 35% of maximal oxygen consumption (VO2max) following the mental challenge. Repeated-measures ANOVAs were used to assess state anxiety (SAI), cardiovascular variables, EPI, NE, and CORT levels across time between conditions. Participants reported significantly greater increases in SAI scores immediately after the mental challenge, which then decreased post-challenge in both conditions. Neither EPI or NE demonstrated an alteration in levels in either condition, but CORT significantly increased after the mental challenge in both conditions and then maintained a significantly greater level during the MEC compared to the MC condition from midexercise through 15 min of recovery. Area-under-the-curve calculations for CORT was significantly greater in the MEC compared to the MC. Results suggest that the initial mental challenge may have acted to enhance the overall adrenal response to the subsequent anticipation of and actual participation in the low-level physical challenge.

Previous research suggests that sleep deprivation is associated with declines in metabolic activity within brain regions important for judgement and impulse control, yet previous studies have reported inconsistent findings regarding the effects of sleep loss and caffeine on risk-taking. In this study, 25 healthy adults (21 men, four women) completed the Balloon Analog Risk Task (BART) and Evaluation of Risks (EVAR) scale at regular intervals to examine behavioral and self-reported risk-taking propensity during 75 h of continuous sleep deprivation. Participants received either four double-blind administrations of 200 mg caffeine (n=12) or indistinguishable placebo (n=13) gum bi-hourly during each of the 3 nights of sleep deprivation. No significant effects of drug group or sleep deprivation were evident on the BART or EVAR when measured at 51 h of wakefulness. However, by 75 h, the placebo group showed a significant increase in risk-taking behavior on the cost-benefit ratio and total number of exploded balloons on the BART, whereas the caffeine group remained at baseline levels. On the EVAR, several factors of self-reported risk-taking propensity, including total risk, impulsivity and risk/thrill seeking, were reduced among subjects receiving caffeine across the 3 days of sleep deprivation, but remained at baseline levels for the placebo group. These results suggest that 3 nights of total sleep deprivation led to a significant increase in behavioral risk-taking but not self-reported perception of risk-propensity. Overnight caffeine prevented this increase in risky behavior., (Published 2010. This article is a US Government work and is in the public domain in the USA.)

This double-blind, placebo-controlled, within-subject experiment examined the effects of low-dose caffeine on pain reported during an exhaustive grip task. The grip task consisted of holding a metal block attached to standard Olympic weight plates with the arm at the side until the participants could no longer maintain their grip. Apparently healthy recreationally trained college-aged adults (men, n = 5; women, n = 5) were given either a piece of Stay Alert™ gum that delivered 85% of the effective dose of 100 mg of caffeine in 5 minutes or an identical placebo gum that contained no caffeine. Subsequently, pain perception and ratings of perceived exertion were recorded during an exhaustive grip task every 15 seconds and the overall time to exhaustion. No significant difference was found in time to exhaustion between treatments. A significant main effect of treatment for reported pain (p < 0.001, Φ = 0.377) was observed. Thus, in a population of recreationally trained college-aged adults, low-dose caffeine may attenuate the individual's perception of pain during a grip to exhaustion task.

The purpose of this study was to examine the effects of concurrent physical and mental challenge on stress hormones and indicators of vascular function in firefighters. Twelve professional firefighters exercised at 60% VO(2max) while participating in a computerized Fire Strategies and Tactics Drill (FSTD-fire strategies condition [FSC]), and again at the same intensity without the mental challenge (EAC). No differences in the amount of work performed between conditions existed, although the FSC resulted in greater perceptions of overall workload. Epinephrine and norepinephrine demonstrated significant interaction effects with elevated levels during the FSC. Cortisol responses were significantly elevated across time and for the FSC. Positive correlations were found between cortisol and interleukin-6, endothelin-1, and thromboxane-B(2), and a negative correlation between interleukin-6 and thromboxane-B(2). These results suggest that concurrent challenges results in exacerbated responses of stress hormones and suggests mechanisms that could contribute to the prevalence of cardiovascular events among firefighters., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: U.S. military troops deploying to war zones are currently administered the Automated Neuropsychological Assessment Metrics (ANAM4) Traumatic Brain Injury (TBI) Battery to establish individual neurocognitive performance baselines. In part, the utility of the ANAM4 TBI Battery baseline measurement depends on test-retest reliability of this instrument. The purpose of this report was to evaluate performance following multiple administrations of the ANAM4 TBI Battery: does performance in a repeated measures paradigm constitute a stable, interpretable indication of baseline neurocognitive ability?, Methods: The data presented here are from the ANAM4 TBI Battery administered four times to a group of U.S. Marines in Study 1 and eight times to a group of New Zealand Defence Force personnel in Study 2., Results: The results show practice effect in five of six performance subtests in both Study 1 and Study 2., Discussion: Results are consistent with expectations that multiple test sessions are required to reach stable performance on some computerized tasks. These results have implications for taking ANAM4 TBI Battery practice effects into account in test administration and in data interpretation.

The purpose of this study was to examine the changes in catecholamines (epinephrine [EPI] and norepinephrine [NE]), interleukin-2 (IL-2) and a biomarker of oxidative stress (8-isoprostane) in healthy individuals who were exposed to a dual challenge (physical and psychological stress). Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and 8-isoprostane and between IL-2 and 8-isoprostane following a combined physical and psychological challenge. Seven healthy male subjects completed two experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% VO(2max) for 37 min, while the dual-stress condition (DSC) included 20 min of a mental challenge while cycling. DSC showed greater EPI and 8-isoprostane levels (significant condition by time interaction). NE and IL-2 revealed significant change across time in both conditions. In addition, following dual stress, EPI area-under-the-curve (AUC) demonstrated a positive correlation with NE AUC and IL-2 AUC. NE AUC was positively correlated with IL-2 AUC and peak 8-isoprostane, and peak IL-2 was positively correlated with peak 8-isoprostane in response to a dual stress. The potential explanation for elevated oxidative stress during dual stress may be through the effects of the release of catecholamines and IL-2. These findings may further provide the potential explanation that dual stress alters physiological homeostasis in many occupations including firefighting, military operations and law enforcement. A greater understanding of these responses to stress can assist in finding strategies (e.g. exercise training) to overcome the inherent psychobiological challenges associated with physically and mentally demanding professions.

The purpose of this study examined the changes in heart rate (HR), catecholamines (NE, EPI) and percentages of blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, CD3- CD56+ NK cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes [NK cells+T cells+B cells]) in firefighters exposed to a computerized firefighting strategies and tactics decision-making challenge while participating in moderate intensity exercise. Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and blood lymphocyte subsets following combined mental and physical challenge. Ten professional male firefighters participated in two counterbalanced exercise conditions on a cycle ergometer: (1) 37min of cycle ergometry at 60% VO(2max) (exercise alone condition; EAC) and (2) 37min of cycle ergometry at 60% VO(2max) along with 20min of a computerized firefighting strategies and tactics decision-making challenge (firefighting strategies condition; FSC). FSC elicited significantly greater HR, NE, and EPI when compared to EAC. Both EAC and FSC elicited increases in CD3- CD56+ NK cells. The percentages of CD3+ T cells, CD3+CD4+ helper T cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes were lower immediately following both conditions. Following dual challenge NE AUC was negatively correlated with percentage of CD19+ B cells immediately post challenge, and HR was negatively associated with the percent change in the CD4/CD8 ratio from pre to post challenge. These elevations in NE and heart rate simultaneously in response to the dual challenge suggest greater sympathetic activation that in turn would possibly explain the alteration in the distribution of lymphocyte subsets., (Published by Elsevier Inc.)

Literature examining the effects of aerobic exercise training on excess postexercise oxygen consumption (EPOC) is sparse. In this study, 9 male participants (19-32 yr) trained (EX) for 12 wk, and 10 in a control group (CON) maintained normal activity. VO(2max), rectal temperature (T(re)), epinephrine, norepinephrine, free fatty acids (FFA), insulin, glucose, blood lactate (BLA), and EPOC were measured before (PRE) and after (POST) the intervention. EPOC at PRE was measured for 120 min after 30 min of treadmill running at 70% VO(2max). EX completed 2 EPOC trials at POST, i.e., at the same absolute (ABS) and relative (REL) intensity; 1 EPOC test for CON served as both the ABS and REL trial because no significant change in VO(2max) was noted. During the ABS trial, total EPOC decreased significantly (p < .01) from PRE (39.4 ± 3.6 kcal) to POST (31.7 ± 2.2 kcal). T(re), epinephrine, insulin, glucose, and BLA at end-exercise or during recovery were significantly lower and FFA significantly higher after training. Training did not significantly affect EPOC during the REL trial; however, epinephrine was significantly lower, and norepinephrine and FFA, significantly higher, at endexercise after training. Results indicate that EPOC varies as a function of relative rather than absolute metabolic stress and that training improves the efficiency of metabolic regulation during recovery from exercise. Mechanisms for the decreased magnitude of EPOC in the ABS trial include decreases in BLA, T(re), and perhaps epinephrine-mediated hepatic glucose production and insulin-mediated glucose uptake.

Firefighters are subjected to a combination of physical and mental challenges in the course of their occupational responsibilities. However, due to the ecological factors involved with firefighting, it makes it extremely difficult to examine physiological and psychological changes that occur as a result of these combined challenges. The purpose of this study was to examine the efficacy of a computer-based Fire Strategies and Tactics Drill (FSTD) in eliciting psychological and physiological measures of stress in professional firefighters. In one session, participants exercised at 60% VO(2max) for 37 min (exercise alone condition, EAC), and in the other session the firefighter exercised for an equal amount of time and responded to the FSTD (dual challenge condition; DCC) while exercising. Cardiorespiratory (heart rate [HR], respiration rate [RR], minute ventilation [V(E)], oxygen consumption [VO(2)], ventilatory efficiency [V(E)/VO(2)], and respiratory exchange ratio [RER]) and psychometric measures (State Anxiety Inventory [SAI] and Ratings of Perceived Exertion [RPE]) were obtained throughout the experimental protocols. The NASA Task Load Index was used to assess perceived physical and mental load during each condition. The results demonstrated that the participants perceived overall workload to be higher in the DCC. Repeated measures ANOVAs revealed no differences between the EAC and DCC for VO(2) or RER, but the DCC did elicit significantly greater elevations in HR, RR, V(E), and V(E)/VO(2) compared to the EAC. These results suggest that the FSTD utilized in this study provides an effective method for examining the physiological and psychological responses of firefighters in a research laboratory environment., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Objective: Physical stress (exercise and/or environmental) activates the sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenocortical (HPA) axes. The combination of ultraendurance exercise in the cold presents a unique summated stress to the body. The purpose of this study was to assess the stress hormone response in runners, cyclists, and skiers participating in a 161-km ultraendurance race on a snow-packed course in the Alaskan wilderness., Methods: Forty-four athletes (20 runners, 17 cyclists, 7 skiers) competed on the same course of snow-machine trails and ice roads with each athlete carrying 7 kg of mandatory equipment. Pre-race weight and blood samples were collected 2 days prior to the race start. Post-race measurements were made within 15 minutes of race finish. Hematocrit was measured, and blood samples were analyzed for levels of norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol., Results: Runners lost significant weight (-1.74 kg +/- 1.29) pre-race to post-race. Hematocrit was maintained, and plasma volume increased minimally. Norepinephrine increased significantly pre-race (279.9 pg/mL +/- 356.9) to post-race (691.7 pg/mL +/- 422.6) with no difference among divisions. Epinephrine did not change significantly during the race. Adrenocorticotropic hormone (2.40 pg/mL +/- 2.40 to 19.04 pg/mL +/- 45.38) increased significantly with no difference among divisions. Cortisol increased significantly pre-race (12.03 microg/dL +/- 5.66) to post-race (26.69 microg/dL +/- 5.77), and post-race cortisol was significantly higher in runners vs skiers., Conclusions: These data suggest activation of both the SAM and HPA axes from an ultraendurance race in the cold and reveal the degree of stress hormone responses to this exhausting bout of exercise., (Copyright (c) 2010 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to examine the changes in heart rate (HR), catecholamines (norepinephrine [NE] and epinephrine [EPI]), pro-inflammatory cytokines (interleukin-2 [IL-2] and interleukin-6 [IL-6]), and lymphocytes (CD8+ and CD56+) in firefighters exposed to a decision-making challenge (firefighting strategies and tactics drill) while participating in moderate intensity exercise. Nine professional male firefighters participated in two counterbalanced exercise conditions on a cycle ergometer: (1) 37 min of cycle ergometry at 60% VO(2max) (exercise alone condition ; EAC) and (2) 37 min of cycle ergometry at 60% VO(2max) along with 20 min of a computerized firefighting strategy and tactics decision-making challenge (firefighting strategy condition; FSC). FSC elicited significantly greater HR, NE, EPI, and IL-2 when compared to EAC. These elevations may suggest that the addition of a mental challenge to physical stress can alter the hormonal and immunological responses during firefighting. In addition, this evidence provides insight into the possible mechanisms that explain the link between physical activity, psychological stress, and stress-related diseases., (Published by Elsevier B.V.)