Monitoring Metabolic Status Predicting Decrements in Physiological and Cognitive Performance (2004) / Chapter Skim
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Appendix D: Workshop Manuscripts
Appendix D: Workshop Manuscripts
Pages 237-434
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Army Medical Research arid Materiel Command The ultimate reductionistic view of the Military Operational Medicine Research Program (MOMRP) centers on metabolism as the answer to all questions.
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This kind of feedback will be broadly useful to learning limits of individuals and units. Physiological monitoring is being explored for a wide variety of other military applications, including the forensic "black box" flight recorder-type of analysis of a pilot's mental state after a class A accident, in order to prevent future accidents (Forster, 2002~.
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and blood and urine testing, they assessed hydration status, adrenal stress markers, and corresponding changes in cognitive functioning. Studies by the Air Force explored the use of an electroencephalogram (EEG)
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Fred Hegge in 1996. The goal of the Warf~ghter Physiological Status Monitoring (WPSM)
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, more sophisticated monitoring capabilities and performance predictions are planned that will also include early casualty triage capabilities. EXAMPLES OF CURRENT RESEARCH EFFORTS, AND LEVERAGING FROM RELATED PROGRAMS We have chosen several critical areas for review: hydration and heat production, substrate utilization and energy metabolism, muscle and bone remodeling, and brain function.
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. A peak incidence of stress fractures by about the third week of training was hypothesized to be associated with high rates of bone remodeling stimulated by the training.
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in soldier helmet/spectacles · Intercellular fluid assessment · Whole body water changes Subdermal wicks, boot-sensor body weight tracking with electrolyte and BIA sensors · Sweat markers of calcium and protein metabolism · Altered biomechanics Practical field test systems BIA = bioelectrical impedance analysis. c EMG = electromyogram.
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The Bone Health and Military Medical Readiness research program (supported by the National Osteoporosis and Related Bone Disorders Coalition) is focused on the improved understanding of bone remodeling processes and includes projects that are exploring markers of impending stress fracture injury.
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1994. Physiologic Instrumentation in the Naval Air Warfare Center Human-use Centrifuge to Determine the Effects of Cumulative +Gz on Cognitive Performance.
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. Body Core Temperatures During 96 h of Swamp Phase Ranger Training.
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Consider as recent examples of the operational environment the desert heat conditions of the Persian Gulf the cold, wet weather in Bosnia, and the cold and high altitude challenges in the mountains of Afghanistan. WARFIGHTER PHYSIOLOGICAL STATUS MONITORING CONCEPT Why is physiological monitoring in the field needed?
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thermal/work strain as the physiological strain index (PSI) (Moran et al., 1998)
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~ : - ~ ~ ~_=L: _ ~ - - - ~ ~ I= f - - - ~ eked :~ ~ m ' E ~ E ° , ~ ~ U U I, s ._ u ~ ~ 5 X ° s e 40 W ,u .
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and heart rate, typically derived from an electrocardiogram. The PSI, a lumped core temperature/heart rate index that reflects thermaVwork strain on a scale of 1 to 10 (Moran et al., 1988)
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FIGURE 2 Heart rate, core temperature, and physiological strain index (Moran et al., 1988) in two soldiers engaged in similar training activities during a hot-weather field exercise at the Joint Readiness Training Center, Fort Polk, Louisiana.
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It may be possible in the future to improve electrical resistance-derived estimates of hydration with minimally invasive subdermal electrolyte sensors. Alternatively, future automatic monitoring of urinary excretion rates and solute concentrations may provide valuable insight into hydration status and other aspects of acute soldier health.
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Daily activity patterns can be derived from heart rate or actigraphy (Redmond and Hegge, 19854. The metabolic cost of locomotion can be derived from total weight and foot-ground contact times (pedometry)
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Progressive heat strain moves on a continuum from impaired cognitive function to frank casualty and presents one of the first opportunities to provide commanders with useful predictions of failing performance before a soldier becomes an environmental stress casualty. Collection of field data that includes clear medical outcomes makes it possible to backtrack to earlier indicators of the impending health risk and develop more precise predictive thresholds of individual risk.
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JAppl Physiol 77:933-940.
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1997. Warighter Physiological Status Monitoring (WPSM9: Body Core Temperatures During 96 H of Swamp Phase Ranger Training.
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through both behavioral and physiological responses to thermal stress. When conscious actions to minimize or avoid thermal stress by modifying activity levels, changing clothes, and seeking shelter do not completely negate thermal stress, physiological responses are activated that enhance dissipation or conservation of body heat stores, as appropriate, through alterations in metabolic rate, blood flow between the core and the skin, and sweating.
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Further, an example of how such biomarkers can be used collectively to assess physiological strain and warn of impending health and performance degradation during exposure to heat and cold will be presented. CORE TEMPERATURE Thermal strain is most commonly assessed by the measurement of body core temperature.
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Thermoregulatory Responses to Heat Stress During exercise, core temperature initially increases rapidly and subsequently increases at a reduced rate until heat loss equals heat production and steady-state values are achieved. The core temperature increase represents the storage of metabolic heat that is produced as a by-product of skeletal muscle contraction.
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Evaporation is limited by the vapor pressure of water in air, thus, increasing humidity constrains evaporative heat loss. Uncompensable heat stress occurs when the maximal evaporative cooling capacity of the ambient environment exceeds the amount of evaporative cooling required to dissipate metabolic heat production, and a steady-state core temperature cannot be achieved.
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Heart rate, on the other hand, is easy to measure and is a useful index of thermal strain. During exercise, metabolic rate and heat production may be ten times their levels at rest, and delivery of heat to the skin to achieve core-to-skin heat transfer sufficient for thermal balance must increase proportionately in order to reestablish thermal balance.
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The most recent findings indicate that an increase in PRL in response to exercise heat strain is only observed above a core temperature threshold of 38°C. Thus, while PRL release may provide useful information regarding the development of serotonergic fatigue, the apparent existence of a 38°C temperature threshold for PRL suggests that PRL may be a useful metabolic marker to denote early thermal strain in the heat.
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Physiological Responses to Cold Stress Since the exposed body surface loses heat faster than it is replaced, skin temperature declines upon exposure to cold. When skin temperature falls below about 35°C, a peripheral vasoconstriction is elicited, mediated by increased sympathetic nervous activity that decreases peripheral blood flow and reduces convective heat transfer between the body's core and shell (skin, subcutaneous fat, and skeletal muscle)
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Thus, oxygen uptake is higher, with the increased oxygen uptake representing the added requirement for shivering activity. As metabolic heat production rises with increasing exercise intensity, core and skin temperatures are maintained and the afferent stimulus for shivering declines, causing the shivering-associated component of total oxygen uptake during exercise to also decline.
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(1996) and dietary factors can cause norepinephrine and lactate concentrations to increase and muscle glycogen breakdown to accelerate, so these responses are too nonspecific to provide any useful information about thermal strain during cold exposure.
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Similarly, while the decline in skin temperature during cold exposure does reflect the cold-induced vasoconstrictor response, it is well known that the steady-state skin temperature maintained during exposure to a given cold condition can be influenced by the thickness of subcutaneous fat, fitness level, acclimatization state, and level of exercise or activity, not to mention clothing (Gagge and Gonzalez, 1996; Young, 19964. Thus, if only a single parameter is to be monitored to assess overall thermal strain in the cold, core temperature probably provides more meaningful information than measurements of either shivering or skin temperature.
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and HR! are simultaneous measurements of core temperature and heart rate at a particular time during the heat stress exposure, and TCO and HRO are initial (pre-stress)
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Core body temperature and heart rate are considered reliable physiological parameters for monitoring heat strain, while monitoring skin temperature and sweat rates probably provide less important information due to the wide variability in these responses. The possibility that changes in peripheral metabolites, such as circulating prolactin levels, may provide information about central nervous system heat strain remain to be definitively examined.
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Med Sci Sports Exerc 30:468-472. Pandolf KB, Moran DS.
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The term hypovolemia will define when blood volume is less than "normal." IMPACT ON HUMAN PERFORMANCE Both physical and cognitive performance are impaired proportionally to the magnitude of body water loss incurred (Gopinathan et al., 1988; Sawka, 1988) However, even small losses of body water ~ 1-2 percent body mass IBM]
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In addition, exercise heat stress alters transcompartmental and transcapillary forces that redistribute fluids between various compartments, organs, and tissues (Sawka et al., 20014. For these reasons, the accuracy of most methods used to assess hydration status is limited by the circumstances in which they are measured and the purposes for which they are intended.
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Likewise, plasma volume decreases with dehydration, and this response varies due to the type of dehydration (isoosmotic or hyperosmotic) , physical activity, physical fitness, and heat acclimatization status (Sawka, 1988~.
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Urinary markers of hydration status include urine specific gravity (USG) , urine osmolality (UOSmo~' and urine color.
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SOURCE: Reprinted, with permission Sawka and Coyle (1999) Influence of body water and blood volume on thermoregulation and exercise performance in the heat.
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Clearly, the use of daily body weight should be used in combination with another hydration assessment technique to dissociate gross tissue losses from water losses if long-term hydration status is of interest. Signs and Symptoms of Dehydration In the early stages of dehydration, no signs and symptoms are apparent.
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Moreover, BIA has limited utility to assess hydration status in the field for reasons previously described. It is possible that other technological advances may allow evaluation of other measures (e.g., muscle water content)
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Med Sci Sports Exerc 28:S36-S41.
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Med Sci Sports Exerc 30:15981602.
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For a given individual, over a short term, heart rate is proportionate to workload, and heart rate is much easier to measure than workload.
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The 5-minute workout should be repeated at a greater workload defined as a heart rate of 10 beats per minute higher and the blood lactate should be rechecked. Then the workout and lactate measurement should be repeated each time with a heart rate of 5 beats per minute more.
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Montain, U.S. Army Research Institute of Environmental Medicine MILITARY RELEVANCE OF MONITORING INSULIN-LIKE GROWTH FACTOR-I Mission success in military tactical environments dictate that the warfighter be able to perform prolonged physical exertion in the face of food and sleep restriction (i.e., military operational stress)
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For this reason, periodic assessment of the growth hormone/insulin-like growth factor axis may have utility for sustaining warfighter health and performance. In direct support of the Objective Force Warrior's vision of revolutionizing soldier performance by aggressively employing science and technology efforts that enhance the warfighter's survivability, lethality, sustainment, and mobility on the modern battlefield, The Military Performance and Military Nutrition Division of the U.S.
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This paper initially describes the complex nature of IGF-I regulation and relevance for the military, then it describes initial work characterizing the IGF-I response to military operational stress. The experimental outcomes suggest that IGF-I has potential value as a biomarker of nutritional strain during operational stress.
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The course includes multiday periods consisting of near-continuous physical activity, energy restriction and sleep deprivation. In the first
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Average energy expenditures were ~ 4,000 kcal/day. At the end of the course, the participants had lost 13 to 16 percent of their initial body mass, ~ 65 percent of their fat mass, and 7 percent of their initial lean body mass.
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, a blood sample was obtained after a week of access to food that was preceded by multiple days of energy restriction (~ 1,700 kcal/day) coupled with high-energy expenditures (> 4,500 kcal/day)
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They also had blood samples drawn on days 1, 3, and 4 of the experimental period that included the physical performance tests, near-continuous physical activity (energy expenditure ~ 4,500 kcaVday) , energy restriction (~ 1,600 kcal/day)
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or a group receiving a similar amount of energy but with sufficient added protein to receive approximately 1.0 g protein/kg body mass/day. The group was participating in an 8-day field exercise consisting of sustained physical activity (total daily energy expenditure measured in previous iterations has ranged from 17-25 MJ/day)
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To study whether the dried blood spot methodology could track IGF-I responses to military operational stress, both blood spots and conventional blood samples were collected in a recent field study that manipulated dietary protein intake (described above)
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Future Directions and Enablers for the Objective Force Warrior The data collected on the physiological responses to military operational stress support the potential utility of IGF-I as a metabolic sensor of energy status. IGF-I declines rapidly to energy restriction and remains a viable indicator of an altered energy state until the stressor is removed.
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. Soldiers are exposed to rigorous physical training and military operational stress.
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1999. Protein and amino acids: Physiological optimization for current and future military operational scenarios.
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2003b. Measurement of insulin-like growth factor-I during military operational stress via a filter paper blood spot assay.
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The predominant contributor to the variations of EEis physical activity. Unlike most civilian populations, soldiers are often subjected to negative energy balance (EE significantly exceeds EI)
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Methods of Assessing Physical Activity Studying the relationship between physical activity and health in humans is complicated by the highly variable nature of physical activity. A particularly challenging area has been the development and application of accurate, valid, and cost-effective techniques to quantify physical activity under field conditions (Paffenbarger et al., 1993; Washburn and Montoye, 1986; Wilson et al., 1986~.
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Objective Methods Objective methods for current measurements of physical activity mainly consist of mechanical/electronic devices. Since walking and running are the most common types of physical activities, step counters are often used estimate overall activity levels.
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Works from the Vanderbilt Energy Balance Lab Equipped with the state-of-the-art whole-room indirect calorimeter at Vanderbilt, we are in a unique and ideal environment to develop and validate portable activity monitors for EEACT predictions. The room calorimeter is a small, airtight environmental room (2.6 x 3.3 x 2.3 m3, 19,500 L in net volume)
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Body movements were simultaneously measured using the same Tritrac-R3D biaxial
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~:='y';~5 ~ o ~ o ~ ~ o ~ ~ (14 bZ/r~) pal rUIllsa ~~ 1 ~ ~^ ~ ~ ~ ~ ~ .
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in or on 11 11 cO 1 a, o a' ~ _1 ~ ; - - -go- - - - i- - - - - - - - - E~ ~ l 1 ~ o (/)
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Comparison between EE measured in the whole-room indirect calorimeter, estimated by the ActiWatch, the Tritrac-R3D, and the ActiWatch and Tritrac-R3D monitors combined. METs = metabolic equivalents, calculated as ratio of individual energy expenditure and resting energy expenditure.
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1 000 FIGURE 4 Total energy expenditure of physical activity (EEACT) in 12 healthy women during two 24-hour periods (identical protocol)
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, while the internal stress from the imbalance of high total energy demands versus low energy intake, sleep deprivation, fatigue, and psychological stress (Nindl et al., 2002; Troumbley et al., 1990) may further exacerbate the complexity of the physical activity and EEACT estimations.
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An example is the use of heart-rate monitors, a simple and objective method for the estimation of EE during certain levels of physical activity and exercise (Spurr et al., 19864. Moreover, heart rate monitoring may facilitate the measurements of fatigue, state of hydration, body temperature changes, and emotional state (stress)
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1994. Assessment of energy expenditure for physical activity using a biaxial accelerometer.
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2002. Physical performance responses during 72 h of military operational stress.
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1988. Energy expenditure from minute-by-minute heart rate recording: Comparison with indirect calorimetry.
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Both transform chemical energy into heat and mechanical work (Hill, 1950~. Yet, for skeletal muscle during locomotion, the relative yields of heat and work are not Filly known (Alexander, 1992; Taylor, 1994; van Ingen Schenau, 1998~.
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Just as automobiles perform mechanical work to overcome inertia and wind resistance, human muscles were thought to convert chemical energy into the mechanical energy and work necessary to repeatedly lift and accelerate the body's center of mass and limbs during each stride. However, two important distinctions differentiate human locomotion produced by muscular contractions from that of an automobile powered by a gasoline engine.
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~ .~...... All Work + Heat Heat Chemical energy transformed Velocity (VNmax)
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Although the chemical energy transformed during walking and running has been established for many decades, the proportion converted into mechanical work is not known. Uncertainty regarding the completeness of mechanical energy transfers within each stride has precluded accurate quantification of the relative portions provided from stored mechanical versus stored chemical energy
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This assumption provided them with a seemingly logical explanation for the chemical energy transformations that had
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To date, these approaches have yielded neither consistent quantitative explanations, nor successful independent predictions of the quantities of chemical energy known to be transformed. The alternative possibility, that the chemical energy transformed during human locomotion is not converted into mechanical work, but almos fully into heat, enjoys support from a growing body of experimental evidence.
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Reprinted by permission of Henry Holt and Company, LLC) , while during running, the gravitational and elastic potential energy are transferred by passive stretch and recoil of tendon springs (B)
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to hypothesize that the energy muscles require for force production is the predominant factor in determining the quantities of chemical energy transformed during locomotion. These investigators recognized that the time-averaged vertical force applied to the ground over the course of the stride must equal the body's weight, and that this force can only be applied during the period of footground contact (tc)
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is a constant. This constant, the cost coefficient, represents the metabolic energy transformed in applying the ground force necessary to support the body's weight against gravity.
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The assumption of complete conservation of mechanical energy allowed Taylor and colleagues to establish a link between the chemical energy transformed during locomotion and whole-body mechanics that had been previously lacking. Taylor's hypothesis applied across a 4,500-fold range in the body sizes of running and hopping animals, a 10-fold range of speeds, and to several different gaits.
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The greater the share of the mechanical energy provided conservatively by the pendulum, the smaller the demand on skeletal muscle to convert chemical energy into mechanical work during each stride. This idea can be evaluated by considering two metabolic variables introduced previously: the metabolic energy transformed per unit distance, and the metabolic energy transformed per unit of force applied to the ground (i.e., the cost coefficient; C in Figure 5~.
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Cost Coefficient (Energy/force) A B C \ / Speed FIGURE 5 Metabolic rate (A)
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transformed. Successful sensing would allow the metabolic energy transformed during locomotion to be monitored during the daily lives of soldiers, hikers, medical patients, and others.
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loco FIGURE 7 Rates of chemical energy transformation in the body estimated by footground contact time monitors and those measured directly using indirect calorimetry. SOURCE: Reprinted, with permission Hoyt et al.
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These estimates were so precise that accurate values for Michael Johnson's instantaneous speeds, stride frequencies, and lengths were available for every step of the races monitored (Figure 9~. More recently, the commercial version of the foot-ground contact monitors were used in combination with heart rate monitors to obtain estimates of the body's maximal rate of chemical energy transformation from aerobic metabolism, or VO2maX (Weyand et al., 2001~.
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Hills and substrate quality can alter the mechanics of locomotion, the activity of the skeletal muscles, and the quantities of chemical energy transformed. Under these and other circumstances, significant challenges to biological understanding and sensor development remain.
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The progress made thus far in the ability to monitor speed, distance, metabolic rate, and maximum aerobic power from sensors in field settings would have been difficult to imagine a decade ago. The foundation for this monitoring progress was the experimental work that differentiated the passive and active mechanical aspects of human locomotion.
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1977. Mechanical work in terrestrial locomotion: Two basic mechanisms for minimizing energy expenditure.
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Med Sci Sports Exerc 20:331337. Weyand P
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Consequently, when considering potential markers for changes in protein turnover in muscle, it is necessary to evaluate potential candidates in terms of the ability to reflect changes in the net balance between synthesis and breakdown. The fundamental processes that control the balance between muscle protein synthesis and breakdown are shown in Figure 1.
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Thus, under normal physiological conditions, changes in concentrations of essential amino acids cannot provide insight into the rates of muscle protein synthesis, breakdown, or the balance between them.
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Thus, in critically ill patients, an isolated increase in phenylalanine may reflect liver failure as much as net muscle protein breakdown. The nonessential amino acids alanine and glutamine are the principal means by which nitrogen is transferred from muscle to the liver for eventual excretion as urea.
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Thus, urinary excretion of 3-MH may be problematic to use as a measure of skeletal muscle protein turnover. Determination of arterialvenous differences of 3-MH across muscle may be more useful in that regard.
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Coupled with ingestion of labeled 3-MH and measurement of the decay in enrichment, it is possible to distinguish the contribution of changes in muscle protein breakdown to the overall change in whole body protein turnover. In many, but not all, circumstances, changes in whole-body turnover reflect changes in muscle-protein turnover.
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2003. Human muscle protein synthesis is modulated by exkacellular not intramuscular amino acid availability: A dose response study.
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The onset of pain is also not considered to be a marker for muscle fatigue. Pain by itself is performance limiting and therefore is not a "predictor." The majority of studies of muscle fatigue have assumed that the fatigue is the result of events localized within skeletal muscle (Davies and White, 1981; Edwards, 1981~.
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There are no potential markers for protein turnover. NUTRITIONAL FACTORS Plasma Amino Acids While not directly correlated with protein synthesis, plasma and tissue-free amino acid concentrations and distribution patterns provide useful information on protein metabolism.
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Amino acids provide precursor substrates for the TCA cycle (Young and Marchini, 1990~. If energy expenditure is increased, the need for the replenishment of amino acids is also increased (Wagenmakers, 1998~.
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Numerous studies have explored the use of plasma levels of muscle-derived proteins as indices of muscle damage. The principal markers that have been used are: aspartate amino transferase, lactate dehydrogenase, creatine kinase, myoglobin, fatty-acid binding proteins, carbonic anhydrase isoenzyme III, and myocyte contractile proteins such as troponins and myosin heavy chains (Janssen et al., 1989; Sorichter et al., 1999~.
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But fatigue of central origin it is of potentially great significance to the Army because it could not only affect physical activity, but mental performance as well. Two viable hypotheses have been published: the ammonia hypothesis and the tryptophan hypothesis (Davis, 1995~.
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Brain 5-HT is in involved in the control of arousal, sleepiness, and mood, so it is therefore conceivable that brain 5-HT levels could lead to fatigue during and after vigorous physical activity (Blomstrand, 2001~. Indeed, there is a considerable amount of evidence from rodent studies showing that inhibiting the action of 5-HT improves endurance (Blomstrand, 2001~.
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SUMMARY The only amino acid-derived parameter with the potential for predicting future fatigue is measurement of the fasting plasma aminogram during a period of strenuous training (Kingsbury et al., 1998~. If the findings on Olympic athletes can be reproduced with soldiers, measurement of the fasting plasma aminogram during training could have the potential for early identification of subjects prone to early fatigue.
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From page 343... ...
Med Sci Sports Exerc 24:512-520. Davies CT, White MJ.
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1983. 3-Methylhistidine excretion and the urinary 3methylhistidine/creatinine ratio are poor indicators of skeletal muscle protein breakdown.
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2001. Short-term dietary energy restriction reduces lean body mass but not performance in physically active men and women.
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In fact, there is likely to be differential regulation of these two compartments, and this in turn becomes important for targeting approaches aimed at strengthening bone or preventing stress fractures. Several recent lines of evidence support differential regulation of periosteal and endosteal bone turnover.
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Bone is a major site of IGF-I production, principally from early and mature osteoblasts. It is stored within the skeletal matrix bound to IGFBP-5 and IGFBP-2 and released during osteoclast-mediated bone resorption.
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, but that trabecular bone mass is not altered, nor is skeletal expression of IGF-I. In sum, it appears that circulating, but not skeletal, IGF-I controls periosteal growth and modeling, whereas local IGF-I almost certainly plays an important role in trabecular mineralization and acquisition.
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From page 349... ...
In the meantime, more studies are needed to define how circulating IGF-I may predict risk for failure of the cortical skeleton, principally in respect to stress fractures. Randomized controlled trials are needed with periosteal changes as an important end point to define how particular interventions may improve both mineral and structure, thereby optimizing bone strength.
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Bone is a structural tissue that, in common with all structural materials, is subject to fatigue damage and fracture if left unprepared. As living tissue, one has the unique potential for self-repair of fatigue damage via a process termed bone turnover or bone remodeling.
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· Resorption · Formation · BAD FIGURE 1 Relative changes in bone mineral density (BMD) , bone resorption, and bone formation as a function of age.
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BIOCHEMICAL MARKERS OF BONE TURNOVER As osteoclasts breakdown, the skeleton to begin the process of turnover. There is removal of bone mineral (mainly calcium)
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While this could qualify OCN as a marker of formation, as part of the bone matrix it is also released during bone resorption so is really a marker of "turnover," with some resultant loss of sensitivity. A summary of the biochemical markers of bone turnover is presented in Table 1.
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From page 354... ...
anticipated rate of bone loss, but there are only weak correlations between baseline levels of markers and prospectively measured changes in bone mineral density (BMD)
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SUMMARY AND CONCLUSIONS Bone turnover is an efficient mechanism for ongoing repair of microdamage to the skeleton. Stress fractures occur when the rate of accumulation and propagation of microdamage exceeds the capacity of the repair process.
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The first hypothesis is that it is mechanical stress, per se, that causes bone to fail. The second hypothesis is that mechanical loading triggers an increase in bone remodeling activity that causes a transient reduction in bone mass, thereby increasing the vulnerability of bone to damage if mechanical loading continues.
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From page 357... ...
microdamage that occurs as a result of mechanical loading, and (c) exercise-induced changes in physiological factors that increase bone resorption.
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From page 358... ...
For example, in patients with hip prostheses outfitted with telemetrically monitored force sensors, the highest forces were recorded during unexpected movements, such as stumbling (Bergmann et al., 1993, 1995~. However, even when all these factors are considered, it seems unlikely that the development of stress fractures after only a few weeks of intensive physical activity is attributable solely to mechanical stress.
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From page 359... ...
The period of bone resorption lasts about 3 to 4 weeks, with subsequent activation of bone formation activity. If the induction of bone resorption and consequent decrease in bone mass does, indeed, increase the susceptibility of bone to stress fracture, it could be postulated that use of an antiresorptive agent would diminish this risk.
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From page 360... ...
DEVELOPMENT OF STRESS FRACTURES OTHER PHYSIOLOGICAL FACTORS The fact that stress fractures develop in only a few weeks in response to an increase in mechanical loading is temporally consistent with the hypothesis that an increase in bone resorption triggers a decrease in bone mass that transiently increases the vulnerability of bone to fracture. In this context, other physiological factors that may further exaggerate bone resorption or impair the coupling with subsequent bone formation activity should be considered.
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From page 361... ...
, and that the combined effects of estradiol and mechanical stress on bone formation activity are additive or synergistic (Cheng et al., 1997; Kohrt et al., 1995~. Thus, the effectiveness of mechanical loading to favorably affect bone metabolism may be diminished in the estrogen-deficient state or when estrogen receptor function is alerted.
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From page 362... ...
Biomarkers of Mechanical Stress Although it is unlikely that stress fractures develop solely as a result of mechanical loading, the extent of mechanical stress may influence other predictors of stress fracture. The number of loading cycles is thought to be of less importance than the stress magnitude, which could potentially be monitored by load sensors in the shoes.
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From page 363... ...
For example, prostaglandin E2 has been found to play a critical role in the bone formation response to mechanical stress in both isolated cell and in vivo animal models, and the response is abrogated by NSAIDs. Despite the widespread use of NSAIDs by humans, particularly in conjunction with exercise training, there is no knowledge of the potential adverse effects on bone metabolism.
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2001. The impact of lifestyle factors on stress fractures in female Army recruits.
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From page 365... ...
1998. Insulin-like growth factors and bone: The osteoporosis connection revisited.
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From page 366... ...
and cognitive performance. Neural network studies in humans have reported increased activity in the prefrontal cortex during tasks involving executive function and working memory (Goldman-Rakic, 1998~.
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From page 367... ...
When this network is either rigidly coupled or completely uncoupled, the ability to recruit and utilize appropriate neural support to meet a particular demand is hampered and the organism is thus less adaptive. It has been proposed that the prefrontal cortex is taken "off-line" during emotional stress to let automatic, prepotent processes regulate behavior (Arnsten and Goldman-Rakic, 1998~.
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Many tasks important for survival in today's world involve cognitive functions such as working memory, sustained attention, behavioral inhibition, and general mental flexibility. These tasks are all associated with prefrontal cortex activity (Arnsten and Goldman-Rakic, 1998~.
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HRV and cortisol responses were recorded, and subjects were grouped into low- and high-HRV groups. Performance on tasks involving simple and choice reaction times did not differ between these groups.
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From page 370... ...
In: Roberts AC, Robbins TW, Weiskrantz L, eds. The Prefrontal Cortex: Executive and Cognitive Function.
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1990. Beat-to-beat variations of heart rate reflect modulation of cardiac autonomic outflow.
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From page 372... ...
These effecters of the stress system regulate a highly coordinated response aimed at mobilizing energy, increasing arousal, and restoration of homeostasis in the face of threatening stimuli. Other endocrine systems, including the growth hormone/insulin-like growth factor-1 (GH/IGF-1)
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as a viable option for monitoring indices of stress system activity in the field. Biology of the Stress Response and Bone Mass An example of a serious medical consequence resulting from chronic stress is osteoporosis.
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In addition to the obvious physical component of mechanical overload associated with marching for a long period time with heavy loads, it is reasonable to hypothesize that some of the endocrine responses associated with the psychological stress may accelerate bone resorption and decrease bone formation. Specifically, an increase in cortisol and a decrease in IGF-1 (an important contributor to skeletal integrity)
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. Stress fractures are a common problem in young people who engage in vigorous physical activity, especially endurance training.
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A series of biochemical markers of bone turnover, cytokines, and neurohormones may be measured in microliters of specimen, using state-of-the art technologies, such as recycling immunoaffinity chromatography and cytokine chip technology. These techniques require a minimum amount of biological sample, thus overcoming the need for collection of large volumes of blood.
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Sweat determinations of pyridinoline reflected true changes in bone resorption due to metabolic disease and antiresorptive treatments, indicating that these measurements were valid and accurate (Sarno et al., 1999, 2001~. In addition, as pyridinoline in sweat arises from plasma, measurements of pyridinoline in this biological fluid reflect true bone resorption more closely than urine measurements.
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The application of newer technologies, including recycling immunoaffinity chromatography and the cytokine chip technology, described below, should address both challenges (Brown et al., 2000; Phillips et al., 1997~. Recycling Immunoaffinity Chromatography Specimens can be analyzed for cytokines, hormones, biochemical markers of bone turn-over, or any other substance of interest using a 25-pL sample injected into a modified liquid chromatography system, equipped with a panel of 25 to 30 immunoaffinity columns packed with antibody-coated glass beads.
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-la, growth hormone Miscellaneous com- Pituitary adenyl cyclase-activating peptidea, neurotro pounds phin-3a, transforming growth factor 13, leukemia in hibitory factora, gamma interferon-inducible protein 1 ha, epidermal growth factor, ciliary neutrophic fac tor, nerve growth factor, 13 fibroblast growth factora, macrophage inflammatory protein ha a Substance that can be detected in sweat only after a 1 2-min walking-running test. interest, are spotted in appropriate patterns onto rehydrated chips and incubated in a moist chamber for 60 minutes at 37°C.
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In conclusion, the sweat patch provides the opportunity to conduct naturalistic studies outside of the laboratory on a very large number of subjects. Once validated in a reference population, this technique would allow for the early identification of subjects who, because of their individual physiological responses to stress, may be at greater risk during intense training of stress fractures, acute infections, or other stress-related accidents.
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Med Sci Sports Exerc 31:117~1182. Munoz-Torres M, Mezquita-Raya P
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Because brain hypometabolism is assumed to underlie performance deficits, the former would be the "gold standard" biological signal to monitor. Biomarkers of brain metabolism changes during sleep deprivation include blood flow (Braun et al., 1997)
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Effect Size Analysis Data were also explored by generating an effect size estimate (also known as a d statistic) for the relationship between nightly sleep time and each task/dependent variable listed above independent of sleep group assignment (Balkin et al., submitted)
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would be the preferred biological signal to monitor to predict sleep deprivation-induced performance impairments, such markers are currently not Weldable. Therefore, the question of what constitutes a promising metric of general sleep-related performance capacity for use in the operational environment is addressed.
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Tasks in the top rankings for both included PVT, simulated d~iving lane deviations and lane position, SLT, SSS subjective sleepiness self-ratings, and serial addition/subtraction speed. That SLT accounted for the most variance by the effect size technique is perhaps not surprising since it could be argued that SLT is the most "direct" measure of sleep loss in that it actually gauges sleep (onset)
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studies will be performance metrics, with a vision toward integration of newer, "high-risk/high-payoff~' technologies, such as analyses of changes in gene expression across sleep deprivation/sleep restriction, and how such changes in gene expression relate to specific performance metrics. Also needed in the near-term are studies describing the exact relationship between sleep deprivation-induced brain hypometabolism and specific aspects of cognitive performance to determine whether there is actually a need for measuring hypometabolism directly.
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2000. Neural basis of alertness and cognitive performance impairments during sleepiness.
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Fatigued pilots tend to decrease their physical activity, withdraw from social interactions, and lose the ability to effectively divide mental resources among different tasks. These effects are compounded by the fact that increased sleepiness in the cockpit is associated with less consistent performance and deteriorations in vigilance (Dinges, 1990~.
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supports the feasibility of continuous, real-time monitoring. In addition, numerous ground-based studies have established the sensitivity of EEG activity to work-related stressors such as sleep deprivation.
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Grass E5SH electrodes were used to detect EEG. Subjective mood evaluations were made in the laboratory using the Profile of Mood States (POMS)
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The analysis of theta activity revealed session main effects at Fz, Cz, and Pz primarily because of linear increases from the first to the last sessions of the deprivation cycle. Eyes main effects at all three electrodes were due to less theta at eyes-open than at eyesclosed.
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Profile of Mood States One-way ANOVAs of the scales from the POMS given at 2100, 2155, 0200, 0255, 0700, and 0755 revealed main effects on tension-anxiety, vigoractivity, fatigue-inertia, and confusion-bewilderment (p < 0.05~. These occurred because mood deteriorated as the hours of continuous wakefulness increased.
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Although less than half of MATB outcome measures apparently were sensitive to the effects of sleep loss and fatigue, the ones that did degrade seem particularly pertinent to aviator performance. Degradations in the reaction time to warning lights and out-of-bounds dial indications, along with more variable performance and increased tracking errors, became more pronounced as the amount of sleep deprivation progressed.
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1995. Effect of total sleep deprivation on reaction time and waking EEG activity in man.
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1987. Psychophysiological measures of drowsiness as estimators of mental fatigue and performance degradation during sleep deprivation.
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Army Research Institute of Environmental Medicine BACKGROUND 399 Basic scientists and clinicians have been searching for biochemical markers of cognitive state for many years. Unfortunately, little progress has been made with regard to identification of markers that, in normal individuals, relate metabolic status to cognitive function or assess general cognitive state.
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and triglycerides, may, in healthy individuals, be better markers of cognitive state, and perhaps metabolic status, than glucose. The Inherent Difficulty of Identifying Biochemical Markers for Cognitive State Although there is great need for objective markers of cognitive state, there are a variety of reasons why it has been extremely difficult to define reliable markers for brain function in normal humans.
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In military as well as civilian populations, a consistent relationship between plasma glucose within the normal range and cognitive performance has never been demonstrated. Carbohydrate administration can clearly enhance physical performance when high levels of energy are being expended.
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. The scenario simulated combat-like conditions, specifically a high-intensity, light infantry operation in a hostile environment, by combining multiple stressors: near total sleep deprivation; continuous physical activity; substantial physiological, environmental, and psychological stress; and simulated combat-like activities.
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In situations like Marine basic training, where volunteers are available for only brief periods of time and a large number of subjects must be tested simultaneously, they are the only practical way of gathering frequent and detailed data on cognitive state. At both the infield and post-field testing sessions we observed very large decrements in cognitive performance, including changes in fundamental functions like vigilance (p < 0.001; Figure 1)
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When these markers FFA, triglycerides, fructosamine, and DHEA-S were aggregated in multiple regression models with weight loss included as a predictor variable, ability to predict mood states was increased and r2 values as high 0.40 were obtained, indicating the regression model could account for 40 percent of the overall variance associated with certain mood states. The magnitude of the relationships we observed between mood states and these biochemical markers, both as individual correlations and within multiple regression models, was surprising.
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changes in mood state in female trainees as assessed by the Profile of Mood States (POMS) over the course of Marine basic training.
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plasma concentration of the indicated marker in female trainees over the course of Marine basic training. A reference value ~ 2 standard deviations)
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a, cd EN c)
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From page 409... ...
o v ~ - 4 be ·u)
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From page 410... ...
Tryptophan, because it is a rate-limiting precursor of the neurotransmitter serotonin, serves a critical CNS need (Lieberman, 1999; Lieberman et al., 1997~. It should be emphasized that many of the metabolizes and hormones evaluated in the Marine basic training study, including glucose, corticotrophin-releasing factor, cortisol, and leptin which, based on their known associations with brain function, might have been expected to be associated with cognitive function, but were not (Table 1~.
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JAppl Physiol 88:1820-1830. Jameison K, Dinan TG.
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1999. Amino acid and protein requirements: Cognitive performance, stress, and brain function.
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CIRCULATING PLASMA MARKERS OF COGNITIVE STATUS ODORS AS BIOMARKERS Gary K Beauchamp, Monell Chemical Senses Center Chemical signals (herein termed body odors or just odors)
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Finally, speculation on the future use of body volatiles in monitoring physiological status will be provided. MESSAGES IN BODY ODOR Work with body odors in nonhuman animals has clearly demonstrated that a variety of messages is transmitted and that these messages influence the behavior and physiology of the receiver.
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Consider gender first. Although basic biological gender is fixed at conception, many data indicate that body odors reflecting this do change over the course on an individual's life.
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BODY ODORS INDICATIVE OF OTHER PHYSIOLOGICAL STATES Very little experimental work has been conducted on odors indicative of emotion (e.g. fear, anger, happiness)
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These studies are admittedly tentative but in light of their implications, a number of investigators are following them up. BODY ODORS AS SIGNALS: FUTURE PROSPECTS Based on studies with nonhuman animals and much more limited work with humans, it is safe to say that body odor is a rich potential medium for monitoring physiological states.
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One strategy is to develop devices that mimic or even use biological principles to detect specific body odors. Particularly attractive is the idea that one might be able to express olfactory receptors in a device that monitors their activity using, for example, fluorescence to express overall patterned activity.
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2002. Presence of mouse mammary tumor virus specifically alters the body odor of mice.
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in order to predict long-term adaptations reflecting changes in either the phenotype and/or net protein balance (anabolic and catabolic states) in skeletal muscle.
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APPENDIXD 421 tional/translational processes cannot match that of degradation, then the muscle enters a state of catabolism, which results in net protein loss leading to its atrophy. Thus, it is important to note that all of the processes operating in the cas
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Activity Paradigms for Studying Adaptations in Skeletal Muscle: Animals Models In this paper we will focus on three different activity/inactivity paradigms: (~) a model of chronic functional overload (FO)
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METHODS AND MATERIALS All the animal projects involved adult, female rats. Functional overload and resistance training procedures were as described in detail elsewhere (Adams et al., 2002; Baldwin and Haddad, 2001; Haddad and Adams, 2002~.
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In addition to the response of growth factors, we also determined if there are rapid adaptive changes in the machinery that translates mature mRNA into protein (Figure 1~. Therefore, we examined levels of total RNA in skeletal muscle, since approximately 85 percent of the RNA pool exists as ribosomal RNA.
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FIGURE 3 Soleus insulin-like growth factor-1 (IGF-1) and mechanical growth factor (MGF)
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FIGURE 4 Soleus total RNA concentration and content in response to overload.
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428 MONITORING METABOLIC STY TUS -~-Con (A)
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These enzymes define the process whereby specific proteins become targeted for degradation by the proteasome system, which is the major pathway for protein degradation in muscle cells. These collective responses provide a mechanism to rapidly reduce muscle mass by decreasing the ability of the muscle to accumulate protein while increasing the processes for decreasing protein pools, thereby creating a catabolic state and net protein loss.
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From page 430... ...
that can mimic, to a certain extent, the gross responses seen in animal models of hypertrophy and of atrophy) , questions arise as to whether acute changes in the mechanical stress imposed on human skeletal muscle induce the same type of responses as reported herein for rodent muscle.
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The resistance training of the ambulatory subjects did not significantly enhance muscle mass or muscle strength beyond that which was observed for the ULLS plus trained group. Biopsies were obtained on each subject at the beginning and end of the experimental protocol.
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0.50 0.25·— (,, ~ ~ o.oo ._ Hi_ I,, -o 2 -0.50 * ULLS RE ULLS+RE FIGURE 8 Changes in total RNA concentration (A)
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SUMMARY AND CONCLUSION In this report we have demonstrated that skeletal muscle of both animal and human subjects possess a high level of plasticity (ability to change in response to altered environment) of gene expression in response to altered states of loading and/or mechanical stress.
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Skeletal muscle protein composition following 5 weeks of ULLS and resistance exercise countermeasures. J Grav Physiol.
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Key Terms
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