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NASA NTRS2014

Customizing Countermeasure Prescriptions using Predictive Measures of Sensorimotor Adaptability

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the readapation phase following a return to a gravitational environment. These alterations may lead to disruption in the ability to perform mission critical functional tasks during and after these gravitational transitions. Astronauts show significant inter-subject variation in adaptive capability following gravitational transitions. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of a countermeasure comprised of a training program designed to enhance sensorimotor adaptability. Due to this inherent individual variability we need to develop predictive measures of sensorimotor adaptability that will allow us to predict, before actual space flight, which crewmember will experience challenges in adaptive capacity. Thus, obtaining this information will allow us to design and implement better sensorimotor adaptability training countermeasures that will be customized for each crewmember's unique adaptive capabilities. Therefore the goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to design sensorimotor adaptability training countermeasures that are customized for each crewmember's individual sensorimotor adaptive characteristics. To achieve these goals we are currently pursuing the following specific aims: Aim 1: Determine whether behavioral metrics of individual sensory bias predict sensorimotor adaptability. For this aim, subjects perform tests that delineate individual sensory biases in tests of visual, vestibular, and proprioceptive function. Aim 2: Determine if individual capability for strategic and plastic-adaptive responses predicts sensorimotor adaptability. For this aim, each subject's strategic and plastic-adaptive motor learning abilities are assessed using a test of locomotor function designed specifically to delineate both mechanisms. Aim 3: Develop predictors of sensorimotor adaptability using brain structural and functional metrics. We will measure individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI). We decided to complete the data collection for Specific Aims 1, 2 and 3 simultaneously on the same subjects to increase data capture. By having the same subjects perform all three specific aims we can enhance our ability to detect how a wider range of factors can predict adaptability in a specific individual. This provides a much richer database and potentially a better understanding of the predictive power of the selected factors. In this presentation I will discuss preliminary data obtained to date.

Bloomberg, J. J.↗

NASA NTRS2017

Practical Applications of Cables and Ropes in the ISS Countermeasures System

National Aeronautics and Space Administration (NASA) uses exercise countermeasures on the International Space Station (ISS) to maintain crew health and combat the negative effects of long-duration spaceflight on the human body. Most ISS exercise countermeasures system (CMS) equipment rely heavily on the use of textile and wire ropes to transmit resistive loads and provide stability in a microgravity environment. For a variety of reasons, including challenges in simulating microgravity environments for testing and limits on time available for life cycle testing, the textiles and wire ropes have contributed significantly to on-orbit planned and unplanned maintenance time. As a result, continued ground testing and on-orbit experience since the first expedition on the ISS in 2000 provide valuable data and lessons learned in materials selection, applications, and design techniques to increase service life of these ropes. This paper will present a review of the development and failure history of textile and wire ropes for four exercise countermeasure systems-the Treadmill with Vibration Isolation and Stabilization (TVIS) System, Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS) System, Interim Resistive Exercise Device (IRED), and the Advanced Resistive Exercise Device (ARED)-to identify lessons learned in order to improve future systems. These lessons learned, paired with thorough testing on the ground, offer a forward path towards reduced maintenance time and up-mass for future space missions.

Svetlik, Randall G.↗

NASA NTRS2017

Gradient Compression Garments as a Countermeasure to Post-Space Flight Orthostatic Intolerance: Potential Interactions with the Maximum Absorbency Garment

Astronauts and cosmonauts may experience symptoms of orthostatic intolerance during re-entry, landing, and for several days post-landing following short- and long-duration spaceflight. Presyncopal symptoms have been documented in approximately 20% of short-duration and greater than 60% of long-duration flyers on landing day specifically during 5-10 min of controlled (no countermeasures employed at the time of testing) stand tests or 80 deg head-up tilt tests. Current operational countermeasures to orthostatic intolerance include fluid loading prior to and whole body cooling during re-entry as well as compression garments that are worn during and for up to several days after landing. While both NASA and the Russian space program have utilized compression garments to protect astronauts and cosmonauts traveling on their respective vehicles, a "next-generation" gradient compression garment (GCG) has been developed and tested in collaboration with a commercial partner to support future space flight missions. Unlike previous compression garments used operationally by NASA that provide a single level of compression across only the calves, thighs, and lower abdomen, the GCG provides continuous coverage from the feet to below the pectoral muscles in a gradient fashion (from approximately 55 mm Hg at the feet to approximately 16 mmHg across the abdomen). The efficacy of the GCG has been demonstrated previously after a 14-d bed rest study without other countermeasures and after short-duration Space Shuttle missions. Currently the GCG is being tested during a stand test following long-duration missions (~6 months) to the International Space Station. While results to date have been promising, interactions of the GCG with other space suit components have not been examined. Specifically, it is unknown whether wearing the GCG over NASA's Maximum Absorbency Garment (MAG; absorbent briefs worn for the collection of urine and feces while suited during re-entry and landing) will interfere with the effectiveness of the GCG or conversely whether the GCG will reduce the fluid absorption capabilities of the MAG. Methods: This operational, directed study, will (1) determine whether the effectiveness of the GCG is affected by the MAG with regard to cardiovascular responses to head-up tilt, the standard orthostatic intolerance test employed for astronauts and bed rest subjects; (2) determine whether the effectiveness of the MAG is compromised by the GCG tested by injecting a standard fluid volume (950 ml in 3 separate simulated "urine voids") at a standardized rate (30 ml/sec); and (3) determine whether comfort is affected by wearing the MAG under the GCG using a standardized questionnaire. Results from this study will guide future development and operational use of the GCG and MAG to maximize crew health, safety, and comfort.

Lee, S. M. C.↗

NASA NTRS2017

MS Non-Pharmacological Countermeasure to Decrease Landing Sickness and Improve Functional Performance While Disorientad

Upon return from spaceflight, a majority of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. No operational countermeasure currently exists to mitigate the risks associated with these sensorimotor disturbances. Stochastic resonance (SR) can be thought of simply as "noise benefit" or an increase in information transfer by a system when in the presence of a non-zero level of noise. We have shown that low levels of stochastic vestibular stimulation (SVS) improve balance and locomotor performance due to SR (Goel et al. 2015, Mulavara et al. 2011, 2015). Additionally, a study in a 6-hydroxydopamine (6-OHDA) hemi-lesioned rat model of Parkinson's disease demonstrated improvements in locomotor activity after low-level SVS delivery possibly due to an increase in nigral gamma-aminobutyric acid (GABA) release in a dopamine independent way (Samoudi et al. 2012). SVS specifically increased GABA release on the lesioned, but not the intact side. These results suggest that SVS can cause targeted alterations of GABA release to affect performance of functional tasks. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008). Magnusson et al. (2000) supported this finding by showing that the administration of a GABAB agonist caused a reversal of the symptoms that is normally seen after unilateral labyrinthectomy. Thus, GABA could play a significant role in reducing MS and promoting adaptability. We have taken advantage of the SR mechanism as a modulator of neurotransmitters to develop a unique SVS countermeasure system to mitigate MS symptoms and improve functional performance after landing. Healthy subjects (n=20) participated in two test sessions, one in which they received +/-400 microA of SVS and one where they received no stimulation (0 microA); the study design was counterbalanced. Subjects began by performing a series of four functional tasks 3-5 times as baseline measurements of task performance. Then, to induce MS, subjects walked an obstacle course with up-down reversing prisms. If they completed the course before achieving our pre-determined level of MS, they were asked to read a poster while making large up-down head movements to a metronome while still wearing the reversing prism goggles. Subjects were stopped every two minutes and asked to report their MS symptoms. Using the Pensacola Scale for motion sickness, test operators evaluated the level of MS of each subject. Once a subject reached an 8 on this scale, which is equivalent to mild malaise, or 30 minutes had passed since the start of the MS induction, this protocol was stopped. Finally, immediately after MS induction, subjects were asked to complete the four functional tasks again. Although, 100% of our subjects experienced at least one MS symptom, only 55% of our subjects experienced stomach awareness to any degree. Without SVS, only 40% of subjects lasted the full 30-minute MS induction protocol, while 65% of subjects lasted the full 30 minutes with SVS, which is nearly a significant increase (p=0.056). In addition, subjects showed significant improvement from baseline when performing a tandem walk and a prone-to-stand test immediately after the MS induction protocol was stopped but the stimulation level was continued. The results are promising and future work includes comparing MS progression between PMZ and SVS directly in subjects that are provoked to a minimum of nausea. Low levels of SVS stimulation may serve as a non-pharmacological countermeasure to replace or reduce the PMZ dosage requirements and concurrently improve functional performance during transitions to new gravitational environments after spaceflight.

Rosenberg, M. J. F.↗

NASA NTRS2016

Biomechanical Modeling of the Deadlift Exercise to Improve the Efficacy of Resistive Exercise Microgravity Countermeasures

During long-duration spaceflight missions, astronauts exposure to microgravity without adequate countermeasures can result in losses of muscular strength and endurance, as well as loss of bone mass. As a countermeasure to this challenge, astronauts engage in resistive exercise during spaceflight to maintain their musculoskeletal function. The Hybrid Ultimate Lifting Kit (HULK) has been designed as a prototype exercise device for an exploration-class vehicle; the HULK features a much smaller footprint than previous devices such as the Advanced Resistive Exercise Device (ARED) on the International Space Station (ISS), which makes the HULK suitable for extended spaceflight missions in vehicles with limited volume. As current ISS exercise countermeasure equipment represents an improvement over previous generations of such devices, the ARED is being employed as a benchmark of functional performance. This project involves the development of a biomechanical model of the deadlift exercise, and is novel in that it is the first exercise analyzed in this context to include the upper limbs in the loading path, in contrast to the squat, single-leg squat, and heel raise exercises also being modeled by our team. OpenSim software is employed to develop these biomechanical models of humans performing resistive exercises to assess and improve the new exercise device designs. Analyses include determining differences in joint and muscle forces when using different loading strategies with the device, comparing and contrasting with the ARED benchmark, and determining whether the loading is sufficient to maintain musculoskeletal health. During data collection, the number of repetitions, load, cadence, stance, and grip width are controlled in order to facilitate comparisons between loading configurations. To date, data have been collected for two human subjects performing the deadlift exercise on the HULK device using two different loading conditions. Recorded data include motion capture, electromyography (EMG), ground reaction forces, device load cell data, photos and videos, and anthropometric data. Work is ongoing to perform biomechanical analyses including inverse kinematics and inverse dynamics to compare different versions of the deadlift model in order to determine which provides an appropriate level of detail to study this exercise. This work is supported by the National Space Biomedical Research Institute through NCC 9-58.

physical exercise↗

NASA NTRS2014

Variable Vector Countermeasure Suit (V2Suit) for Space Habitation and Exploration

The Variable Vector Countermeasure Suit (V2Suit) for Space Habitation and Exploration is a visionary system concept that will revolutionize space missions by providing a platform for integrating sensors and actuators with daily astronaut intravehicular activities to improve human health and performance. The V2Suit uses control moment gyroscopes (CMGs) within a miniaturized module placed on body segments to provide a viscous resistance during movements _ a countermeasure to the sensorimotor and musculoskeletal adaptation performance decrements that manifest themselves while living and working in microgravity and during gravitational transitions during long-duration spaceflight, including post-flight recovery and rehabilitation. Through an integrated design, system initialization, and control systems approach the V2Suit is capable of generating this viscous resistance along an arbitrarily specified direction of down. When movements are made, for example, parallel to that down direction a resistance is applied, and when the movement is perpendicular to that direction no resistance is applied. The V2Suit proposes to be a countermeasure to this spaceflight-related adaptation and de-conditioning and the unique sensorimotor characteristics associated with living and working in 0-G, which are critical for future long-duration space missions. This NIAC Phase II project leveraged the study results from Phase I and focused on detailing several aspects of the V2Suit concept, including a wearable CMG architecture, control steering laws, human-system integration evaluations, developing a brassboard prototype unit as a proof-of-concept, as well as evaluating the concept in the context of future space exploration missions. A human mission to Mars, such as that outlined in the Mars Design Reference Architecture 5.0, provides a framework for determining the concept of operations and requirements for the V2Suit system. Mars DRA 5.0 includes approximately 180 day 0-G transits to- and from- Mars, as well as a 500 day stay on the surface (~3/8-G) (Figure 3). Accordingly, there are four gravitational transitions associated with this mission: 1-G to 0-G (Earth launch), 0-G to 3/8-G (Mars landing), 3/8-G to 0-G (Mars launch), and 0-G to 1-G (Earth landing). This reference mission provided the basis for developing high-level operational requirements to guide the subsequent study and design of the key V2Suit components.

Duda, Kevin R.↗

NASA NTRS2012

Variable Vector Countermeasure Suit (V2Suit) for Space Habitation and Exploration

The "Variable Vector Countermeasure Suit (V2Suit) for Space Habitation and Exploration" is a visionary system concept that will revolutionize space missions by providing a platform for integrating sensors and actuators with daily astronaut intravehicular activities to improve human health and performance. The V2Suit uses control moment gyroscopes (CMGs) within a miniaturized module placed on body segments to provide a "viscous resistance" during movements and a countermeasure to the sensorimotor and musculoskeletal adaptation performance decrements that manifest themselves while living and working in microgravity and during gravitational transitions during long-duration spaceflight, including post-flight recovery and rehabilitation. Through an integrated design, system initialization, and control systems approach the V2Suit is capable of generating this "viscous resistance" along an arbitrarily specified direction of "down." When movements are made, for example, parallel to that "down" direction a resistance is applied, and when the movement is perpendicular to that direction no resistance is applied. The V2Suit proposes to be a countermeasure to this spaceflight-related adaptation and de-conditioning and the unique sensorimotor characteristics associated with living and working in 0-G, which are critical for future long-duration space missions.This NIAC Phase I project focused on detailing several aspects of the V2Suit concept, including human-system integration, system architecture, computer aided design (CAD) modeling, and closed-loop simulation and analysis. In addition, early-stage breadboard prototyping of several aspects of the V2Suit system modules enabled characterization of expected performance and identified areas for further research and development to enable operational implementation of the V2Suit. In particular, potential challenges with integration of commercial-off-the-shelf components were identified. The key enabler for operational use and adoption of the V2Suit is a low-profile body worn form factor that does not interfere with normal, everyday movements and interfaces adequately with the body as to provide the generated gyroscopic torque for the perceptions of movement with a "viscous resistance." These aspects were investigated through mockups using a life-size mannequin, and through body attachment mechanisms on the breadboard prototype. Through the evaluation and investigation of commercially-available components, as well as an identification of desirable form factors, CAD models of the V2Suit modules were developed. These models included all of the required elements and spin motors, flywheel masses, gimbal motors, slip rings, inertial measurement units, motor controllers, and the required mounting brackets/hardware and cabling. The configuration and orientation of the control moment gyroscopes (CMGs) was specified according to results from the modeling, simulation and analysis. Two revisions of the CAD model were investigated through closed-loop simulation of the CMGs, and their ability to generate a resultant reaction force during movement and null undesirable torques due to changes in the direction of the angular momentum vector as a result of the normal body movements.

space missions↗

NASA NTRSDate not supplied

Oxidative Stress and the Neuroconsequences of Spaceflight Environment - Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy

In this project, we will test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. The project will address NASA’s efforts to rapidly advance the characterization of risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of female astronauts, the two most recent NASA Astronaut Corps class selections, comprised of ~50% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. Here, we will determine how key features of the deep space environment may interact to increase risk to crewmembers by negatively impacting health and performance, and identify and develop strategies to characterize and mitigate the potential risks via countermeasures. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18-18FLAG_2-0028.

radiation↗

NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection By Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1.Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. We have completed infection studies of the 3-D biomimetic intestinal tissue models and are currently analyzing the data.

Jennifer Barrila↗

NASA NTRS2024

Effects of Low Dose Radiation and Radiation Countermeasures on Infection By Spaceflight Analogue Cultured Salmonella Using 3-D Biometric Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1. Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. This study has been initiated and data collection is beginning.

Jennifer Barrila↗

NASA NTRS2024

Multidisciplinary Analytics, Visualization, and Reporting Interface for Integrated Countermeasures

Exploration class missions will have communication latency requiring crew members to make decisions more autonomously, with less support from ground personnel. Therefore, new software is needed to provide crew the ability to not only visualize their countermeasures data, but to also derive comprehensive, nuanced, and multidisciplinary insights regarding the health and performance informatics throughout a mission. The Multidisciplinary Analytics, Visualization, and Reporting Interface for Integrated Countermeasures (MAVRIIC) software seeks to establish a centralized approach to countermeasure data visualization that will facilitate a more holistic understanding of crew members' well-being and performance and enable the development of informed and autonomous decision-making support systems aligned with the evolving requirements of Exploration missions. The culmination of MAVRIIC phase 1 (end of FY23) marked the release of a full-stack, cloud-based ground tool displaying visualizations of in-flight exercise data, exercise ground testing, and exercise MEDB reports. Phase 2 of MAVRIIC (FY24) focuses on beginning the expansion of data contents to domains outside of exercise, including functional fitness, sensorimotor, food/nutrition, radiation, bone, and cardio/vision. Phase 3 and phase 4 will comprise enhanced analytics integration and initiation of flight tool development for infusion into the Artemis Program and eventually the Mars Transit Habitat.

Kent Lawrence Kalogera↗

NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

Jennifer Barrila↗

NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1. Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. This study has been initiated and data collection is beginning.

Jennifer Barrila↗

NASA NTRS2002

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

Review↗

DOE OSTI2025

Accelerating countermeasure candidate discovery for A-series chemical warfare agent exposure

The recent alleged use of A-series chemical warfare agents (CWAs) highlights the urgent need to better understand their inhibition of cholinesterase enzymes and the reported shortcomings of traditional oxime countermeasures. Here, using high-throughput (HT) mass spectrometry (MS) technologies, we characterized the largely unknown inhibition kinetics of A-series CWAs on human acetylcholinesterase (hAChE) and its reactivation by oximes, achieving label-free quantitation at rates of up to 7,000 reactions per hour. Our findings indicate i) A-series agents exhibit inhibitory potencies similar to traditional CWAs like sarin and VX, and ii) bipyridinium-based oximes can reactivate A-series-adducted hAChE in vitro, challenging prior reports on oxime efficacy. These results underscore the need for continued exploration of countermeasure candidates against A-series CWAs and demonstrate the potential of HT-MS for rapidly and safely characterizing emerging toxic chemicals.

acetylcholinesterase↗

NASA NTRS2002

Planning strategies for development of effective exercise and nutrition countermeasures for long-duration space flight

Exercise and nutrition represent primary countermeasures used during space flight to maintain or restore maximal aerobic capacity, musculoskeletal structure, and orthostatic function. However, no single exercise, dietary regimen, or combination of prescriptions has proven entirely effective in maintaining or restoring cardiovascular and musculoskeletal functions to preflight levels after prolonged space flight. As human space flight exposures increase in duration, identification, assessment, and development of various effective exercise- and nutrition-based protective procedures will become paramount. The application of adequate dietary intake in combination with effective exercise prescription will be based on identification of basic physiologic stimuli that maintain normal function in terrestrial gravity, and understanding how specific combinations of exercise characteristics (e.g., duration, frequency, intensity, and mode) can be combined with minimal nutritional requirements that mimic the stimuli normally produced by living in Earth's gravity environment. This can be accomplished only with greater emphasis of research on ground-based experiments targeted at understanding the interactions between caloric intake and expenditure during space flight. Future strategies for application of nutrition and exercise countermeasures for long-duration space missions must be directed to minimizing crew time and the impact on life-support resources.

Review↗

NASA NTRS1995

Status and efficacy of countermeasures to physiological deconditioning from space flight

The recent biomedical investigations conducted on the Space Shuttle and Spacelab have provided a wealth of biomedical information, including the ability to test the efficacy of proposed countermeasures. This achievement was made possible by the ability to conduct mechanistic and control-interventive studies simultaneously with a large number of individuals over a relatively brief period and to compare these data with results obtained from the Skylab missions. Comparisons between short- and long-duration results were limited to establishing trends or extrapolating from short-duration missions. To date, we have evaluated several protocols involving the lower-body negative pressure (LBNP) device, the bicycle-ergometer, the treadmill and preparations for body-fluid replenishment. In many instances, the traditional means of applying these protocols were not sufficient to protect against space-related deconditioning. This paper will review current countermeasures and compare their efficacy to that of existing protocols. Results from in-flight and ground-based experiments will be presented to illuminate the recommended protocols and procedures.

short duration↗

NASA NTRS2005

Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures

There is little evidence obtained from space flight to support the notion that occurrence of cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks during space flight. Therefore, the development of orthostatic hypotension and instability immediately after return from spaceflight probably reflect the most significant operational risks associated with the cardiovascular system of astronauts. Significant reductions in stroke volume and lower reserve for increasing peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with less circulating blood volume while inadequate peripheral vasoconstriction may be caused partly by hyporeactivity of receptors that control arterial smooth muscle function. A focus for development of future countermeasures for hemodynamic responses to central hypovolemia includes the potential application of pharmacological agents that specifically target and restore blood volume (e.g., fludrocortisone, electrolyte-containing beverages) and reserve for vasoconstriction (e.g., midodrine, vasopressin). Based on systematic evaluations, acute physical exercise designed to elicit maximal effort or inspiratory resistance have shown promise as successful countermeasures that provide protection against development of orthostatic hypotension and intolerance without potential risks and side effects associated with specific pharmacological interventions.

Non-NASA Center↗