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Non-invasive Detection System for Assessment of Oxidative Status


OBJECTIVE: To develop a portable detection system to assess oxidative status of the Warfighter using non-invasive techniques and to determine the effects of micro nutrient interventions. DESCRIPTION: Strenuous physical exertion induced Reactive Oxygen/Nitrogen Species (RONS) production in the muscle has been correlated with degradation of muscle force output, fatigue and muscle soreness in animal and human models(1). RONS are generated during normal metabolic function and have important roles in cell signaling. However, when production of RONS in the body exceeds the body"s innate ability to neutralize them, oxidative stress occurs, compromising physiological function due to cellular damage(2,3). RONS can induce cellular damage by oxidizing lipids, proteins, and DNA(4). Oxidative stress, defined as oxidative damage to cells and tissues caused by unregulated RONS production, contributes to degradation of physical performance and can occur due to environmental and physiological stressors, traumatic injury and physical exhaustion(5). Moreover, oxidative stress is known to play a role in muscle atrophy(6) which is commonly experienced during Warfighter recovery from injury. Oxidative stress stimulates the endogenous antioxidant defense systems, and when intrinsic mechanisms are depleted, oxidative stress may be mitigated by exogenous antioxidants found in foods to maintain cellular homeostasis(7,8,9). Recent studies show that low-level RONS production that occur during exercise/training contribute to beneficial muscle adaptations by inducing up-regulation of antioxidant enzymes(2). Excessive consumption of dietary/supplemental antioxidants has been shown in animal and human models to negatively impact muscle adaptation to exercise and aerobic performance, by blunting RONS production and up-regulation of antioxidant defenses(10). Hence, it is important to maintain beneficial levels of RONS, so as not to compromise Warfighter adaptation to initial military training (IMT), and reduce combat effectiveness. A non-invasive detection system is required to assess/discern the changes between baseline oxidative status and oxidative states involved in muscle adaptation or cellular damage in the context of the effects of dietary interventions and physical performance in healthy and recovering Warfighters. Detection system performance goals include adequate sensitivity, precision and accuracy to determine the influence of dietary intervention on oxidative status biomarkers. A systemic measurement is critical for accurate assessment of overall status. Various biomarkers exist for measuring oxidative status, however, the degree to which they are altered may depend on the physical challenge. Therefore the detection system should also demonstrate effectiveness over a range of physical challenges (e.g., IMT, field training) faced by the Warfighter. Successful quantification of changes in oxidative status that stimulate muscle adaptation and cause cellular damage would enable researchers to recommend nutritional strategies. A non-invasive assessment tool will significantly reduce the overall cost and time needed to sample invasive fluids (e.g., blood), which is generally difficult and not suitable during field research. Proof of beneficial effects of bioactive nutrients on oxidative stress and Warfighter performance has been elusive largely due to technological limitations in measuring blood biomarkers(11, 12). As a result, the evidence is minimal regarding the mechanisms by which environmental stressors and common physical challenges faced by the Warfighter promote oxidative stress and degrade performance. The proposed research tool would facilitate the establishment of accurate baseline oxidative status measurements, to examine effects of dietary interventions and how it relates to Warfighter performance(10). This system will benefit future research designed to understand the relationship between oxidative status, nutrition and Warfighter performance. PHASE I: Initiate design concepts for a non-invasive detection system with a small footprint<100 lb and<4 ft(3). System must be robust (conducive for field research) and designed to operate in extreme temperature (32oF to 120oF) and humidity (20 to 100%) ranges. Conduct feasibility studies utilizing proof of principle. Submit a report describing the science supporting the systemic oxidative status detection system and any proof of concept data. Address any technical barriers. PHASE II: Develop an innovative non-invasive detection system for measuring oxidative status. Design and conduct tests to demonstrate device capabilities. Suggestions for test design follows. Trials should be based on a resting condition and at least 2 typical physical activities (i.e., mandatory morning physical training, field training scenario) performed by the Warfighter. Test detection system by establishing oxidative status at resting baseline and compare to oxidative status during and after a strenuous physical activity [(i.e. maximal graded aerobic exercise performance test on a treadmill, (VO2 Max test)] between placebo vs. antioxidant supplement. Measure at least two previously validated blood biomarkers of oxidative stress to determine cellular damage and verify that changes in oxidative status have exceeded the buffering capacity of intrinsic antioxidant defense systems. Using the data established for the cellular damage study, determine the % change in oxidative status that is associated with training adaptations and performance decrements, also comparing placebo vs. an antioxidant supplement group and account for dietary and physiological variation. Then test detection system in a relevant (field simulated) scenario evaluating the effect of dietary intervention (fruit and vegetable extract or powder) on oxidative status. Time will be built in for proper submission, of all necessary human use protocols, and approval through Institutional Research Board (IRB) and Human Use Research Committee (HURC) in collaboration with USARIEM. Submit monthly progress reports. At the end of Phase II deliver prototype (6) and a final report. The report must include system and study design protocols and data, appropriate documentation such as protocols for operation, instruction manuals, such as sensitivity limitations, test throughput, training, materials required, lifecycle, routine maintenance and disposal requirements. PHASE III: Conduct a field test demonstrating the technology in a Warfighter relevant environment including operation, sensitivity limitations, training, lifecycle, routine maintenance and disposal requirements. Phase III will include DoD/CFD evaluation of detection system. Dual use partners will be identified to co-evaluate device. Possible dual-use may exist; other researchers may use for a similar purpose to assess dietary intervention effects on the oxidative state or to assess oxidative state under certain test conditions; for use in clinical setting to supplement other diagnostic tests; for use by USARIEM and other medical professionals to monitor those most at risk and provide nutritional intervention; or possibly for use in training Warfighters/high performance athletes and for other trainers. Potential interest from DARPA collaborator expressed at"Point of Use Nutritional Diagnostic Devices Workshop"(15 Nov 2010).
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