SEARCH · Engineering Papers

Results for “Countermeasures”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8

All sources NASA NTRS DOE OSTI

NASA NTRS2001

E057: Renal Stone Risk Assessment During Space Flight: Assessment and Countermeasure Validation

Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occur as early as flight day 3-4 in the short duration Shuttle crewmembers. Significant decreases were observed both in fluid intake and urinary output. Other significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During Shuttle missions, the risk of calcium oxalate stone formation increased early in the flight, continued at elevated levels throughout the flight and remained in the increased risk range on landing day. The calcium phosphate risk was significantly increased early in-flight and remained significantly elevated throughout the remainder of the mission. Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the preflight. The calcium oxalate risk was increased relative to the preflight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks postflight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increased risk range throughout the flight and following landing. The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our early investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. The early studies have indicated specific avenues for development of countermeasures for the increased renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures are being tested for their efficacy in mitigating the in-flight risk of renal stones. Maintaining the health and well-being of crewmembers during space flight requires a means of minimizing potential detrimental health effects of microgravity. The formation of a renal stone during flight obviously has severe consequences for the affected crewmember as well as the success of the mission.

Whitson, Peggy A.↗

NASA NTRS2010

Development of an Integrated Countermeasure Device for Use in Long-Duration Space Flight

Prolonged weightlessness is associated with declines in musculoskeletal, cardiovascular, and sensorimotor health. Consequently, in-flight countermeasures are required to preserve astronaut health. We developed and tested a novel exercise countermeasure device (CCD) for use in spaceflight with the aim of preserving musculoskeletal and cardiovascular health along with an incorporated balance-training component. Additionally, the CCD features a compact footprint, and a low power requirement. Methods: After design and development of the CCD, we carried out a training study to test its ability to improve cardiovascular and muscular fitness in healthy volunteers. Fourteen male and female subjects (41.4+/-9.0 years, 69.5+/-15.4Kg) completed 12 weeks (3 sessions per week) of concurrent strength and endurance training on the CCD. Subjects were tested at baseline and after 12 weeks for 1-repetition max leg press strength (1RM), peak oxygen consumption (VO2peak), and isokinetic joint torque (ISO) at the hip, knee, and ankle. Additionally, we evaluated subjects after 6 weeks of training for changes in VO2peak and 1RM. Results: VO2peak and 1RM improved after 6-weeks, with additional improvements after 12 weeks (1.95+/-0.5, 2.28+/-0.5, 2.47+/-0.6 LY/min and 131.2+/-63.9,182.8+/-75.0, 207.0+/-75.0 Kg) for baseline, 6 weeks, and 12 weeks respectively. ISO for hip adduction, adduction, and ankle plantar flexion improved after 12 weeks of training (70.3+/-39.5, 76.8+/-39.2 and 55.7+/-21.7 N-m vs. 86.1+/-37.3, 85.1+/-34.3 and 62.1+/-26.4 N-m respectively). No changes were observed for ISO during hip flexion, knee extension, or knee flexion. Conclusions: The CCD is effective at improving cardiovascular fitness and isotonic leg strength in healthy adults. Further, the improvement in hip adductor and abductor torque provides support that the CCD may provide additional protection for the preservation of bone health at the hip.

Streeper, Tim↗

NASA NTRS2010

Visual Performance Challenges to Low-Frequency Perturbations After Long-Duration Space Flight, and Countermeasure Development

Astronauts experience sensorimotor disturbances after long-duration space flight. After a water landing, crewmembers may need to egress the vehicle within a few minutes for safety and operational reasons in various sea state conditions. Exposure to even low-frequency motions induced by sea conditions surrounding a vessel can cause significant motor control problems affecting critical functions. The first objective of this study was to document human visual performance during simulated wave motion below 2.0 Hz. We examined the changes in accuracy and reaction time when subjects performed a visual target acquisition task in which the location of the target was offset vertically during horizontal rotation at an oscillating frequency of 0.8 Hz. The main finding was that both accuracy and reaction time varied as a function of target location, with greater performance decrements occurring when vertical targets were acquired at perturbing frequencies of 0.8 Hz in the horizontal plane. A second objective was to develop a countermeasure, base d on stochastic resonance (SR), to enhance sensorimotor capabilities with the aim of facilitating rapid adaptation to gravitational transitions after long-duration space flight. SR is a mechanism by which noise can enhance the response of neural systems to relevant sensory signals. Recent studies have shown that applying imperceptible stochastic electrical stimulation to the vestibular system (SVS) significantly improved balance and oculomotor responses. This study examined the effectiveness of SVS on improving balance performance. Subjects performed a standard balance task while bipolar SVS was applied to the vestibular system using constant current stimulation through electrodes placed over the mastoid process. The main finding of this study was that balance performance with the application of SR showed significant improvement in the range of 10%-25%. Ultimately an SR-based countermeasure might be fielded either as preflight training to enhance adaptability, or as a miniature patch-type stimulator worn post flight.

Mulavara, Ajitkumar↗

NASA NTRS2012

Countermeasures to Mitigate the Negative Impact of Sensory Deprivation and Social Isolation in Long-Duration Space Flight

Long-duration space flight presents several challenges to the behavioral health of crew members. The environment that they are likely to experience will be isolated, confined, and extreme (ICE) and, as such, crew members will experience extreme sensory deprivation and social isolation. The current paper briefly notes the behavioral, cognitive, and affective consequences of psychological stress induced by ICE environments and proposes nine countermeasures aimed at mitigating the negative effects of sensory deprivation and social isolation. Implementation of countermeasures aims to maintain successful crew performance and psychological well-being in a long-duration space flight mission.

Bachman, Katharine Ridgeway OBrien↗

NASA NTRS2012

Astronaut Biography Project for Countermeasures of Human Behavior and Performance Risks in Long Duration Space Flights

This final report will summarize research that relates to human behavioral health and performance of astronauts and flight controllers. Literature reviews, data archival analyses, and ground-based analog studies that center around the risk of human space flight are being used to help mitigate human behavior and performance risks from long duration space flights. A qualitative analysis of an astronaut autobiography was completed. An analysis was also conducted on exercise countermeasure publications to show the positive affects of exercise on the risks targeted in this study. The three main risks targeted in this study are risks of behavioral and psychiatric disorders, risks of performance errors due to poor team performance, cohesion, and composition, and risks of performance errors due to sleep deprivation, circadian rhythm. These three risks focus on psychological and physiological aspects of astronauts who venture out into space on long duration space missions. The purpose of this research is to target these risks in order to help quantify, identify, and mature countermeasures and technologies required in preventing or mitigating adverse outcomes from exposure to the spaceflight environment

Banks, Akeem↗

NASA NTRS2013

X1: A Robotic Exoskeleton for In-Space Countermeasures and Dynamometry

Bone density loss and muscle atrophy are among the National Aeronautics and Space Administration's (NASA) highest concerns for crew health in space. Countless hours are spent maintaining an exercise regimen aboard the International Space Station (ISS) to counteract the effect of zero-gravity. Looking toward the future, NASA researchers are developing new compact and innovative exercise technologies to maintain crew health as missions increase in length and take humans further out into the solar system. The X1 Exoskeleton, initially designed for assisted mobility on Earth, was quickly theorized to have far-reaching potential as both an in-space countermeasures device and a dynamometry device to measure muscle strength. This lower-extremity device has the ability to assist or resist human movement through the use of actuators positioned at the hips and knees. Multiple points of adjustment allow for a wide range of users, all the while maintaining correct joint alignment. This paper discusses how the X1 Exoskeleton may fit NASA's onorbit countermeasures needs.

Rea, Rochelle↗

NASA NTRS2013

Benefits, Consequences, and Uncertainties of Conventional (Exercise) Countermeasure Approaches

This presentation will review the pros, cons, and uncertainties of using exercise countermeasures in hypothetical long duration exploration missions. The use of artificial gravity and exercise will be briefly discussed. One benefit to continued use of exercise is related to our extensive experience with spaceflight exercise hardware and programming. Exercise has been a part of each space mission dating back to the 1960's when simple isometric and bungee exercises were performed in the Gemini capsule. Over the next 50 years, exercise hardware improved cumulating in today's ISS suite of exercise equipment: Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), Treadmill (T2) and Advanced Resistive Exercise Device (ARED). Today's exercise equipment is the most robust ever to be flown in space and allows the variety and intensity of exercise that might reasonably be expected to maintain muscle mass and function, bone density and cardiovascular fitness. A second benefit is related to the large body of research literature on exercise training. There is a considerable body of supporting research literature including >40,000 peer reviewed research articles on exercise training in humans. A third benefit of exercise is its effectiveness. With the addition of T2 and ARED to our ISS exercise suite, crew member outcomes on standard medical tests have improved. Additionally exercise has other positive side effects such as stress relief, possible improvement of immune function, improved sleep, etc. Exercise is not without its consequences. The major cons to performance of in‐flight exercise are the time and equipment required. Currently crew are scheduled 2.5 hrs/day for exercise and there is considerable cost to develop, fly and maintain exercise hardware. While no major injuries have been reported on ISS, there is always some risk of injury with any form of exercise There are several uncertainties going forward; these relate mostly to the development of small compact robust effective exercise devices for the next generation of space vehicles. It is becoming increasingly apparent that high intensity exercise is required for maintenance of fitness and functional capability and so future hardware will need to be developed, tested and implemented that allow for a wide variety of exercise, at high intensity while likely involving low mass, volume and power. There are many unanswered issues related to the minimum number and type of exercise devices required for exploration, optimizing exercise prescriptions for these devices, whether a treadmill is absolutely required, and even whether any single countermeasure can adequately protect muscle, bone, cardiovascular and sensorimotor function.

Ploutz-Snyder, Lori↗

NASA NTRS2014

Physiological Observations and Omics to Develop Personalized Sensormotor Adaptability Countermeasures Using Bed Rest and Space Flight Data

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the re-adapation phase following a return to an earth-gravitational environment. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from space flight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual space flight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures that include: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; 3) genotype markers for genetic polymorphisms in Catechol-O-Methyl Transferase, Dopamine Receptor D2, Brain-derived neurotrophic factor and genetic polymorphism of alpha2-adrenergic receptor that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration space flight and an analog bed rest environment. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. These data will be combined with predictor metrics that will be collected prospectively - behavioral, brain imaging and genomic measures; from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗

NASA NTRS2014

Inflight Treadmill Exercise Can Serve as Multi-Disciplinary Countermeasure System

The goals of the Functional Task Test (FTT) study were to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We have previously shown that for Shuttle, ISS and bed rest subjects, functional tasks requiring a greater demand for dynamic control of postural equilibrium (i.e. fall recovery, seat egress/obstacle avoidance during walking, object translation, jump down) showed the greatest decrement in performance. Functional tests with reduced requirements for postural stability (i.e. hatch opening, ladder climb, manual manipulation of objects and tool use) showed little reduction in performance. These changes in functional performance were paralleled by similar decrements in sensorimotor tests designed to specifically assess postural equilibrium and dynamic gait control. The bed rest analog allows us to investigate the impact of axial body unloading in isolation on both functional tasks and on the underlying physiological factors that lead to decrements in performance and then compare them with the results obtained in our space flight study. These results indicate that body support unloading experienced during space flight plays a central role in postflight alteration of functional task performance. These data also support the concept that space flight may cause central adaptation of converging body-load somatosensory and vestibular input during gravitational transitions [1]. Therefore, we conclude that providing significant body-support loading during inflight treadmill along with balance training is necessary to mitigate decrements in critical mission tasks that require dynamic postural stability and mobility. Data obtained from space flight and bed rest support the notion that in-flight treadmill exercise, in addition to providing aerobic exercise and mechanical stimuli to the bone, also has a number of sensorimotor benefits by providing: 1) A balance challenge during locomotion requiring segmental coordination in response to a downward force. 2) Body-support loading during performance of a full-body active motor task. 3) Oscillatory stimulation of the otoliths and synchronized periodic foot impacts that facilitate the coordination of gait motions and tune the full-body gaze control system. 4) Appropriate sensory input (foot tactile input, muscle and tendon stretch input) to spinal locomotor central pattern generators required for the control of locomotion. Forward work will focus on a follow-up bed rest study that incorporates aerobic and resistance exercise with a treadmill balance and gait training system that can serve as an integrated interdisciplinary countermeasure system for future exploration class missions.

Bloomberg, J. J.↗

NASA NTRS2014

Fatigue in U.S. Astronauts Onboard the International Space Station: Environmental Factors, Operational Impacts, and Implementation of Countermeasures

Since 2000, US astronauts have been supporting missions up to a six month duration on the International Space Station (ISS). Crewmembers have experienced fatigue for reasons similar to military deployments. Astronauts experience psychological stressors such as heavy workloads, extended duty periods, circadian misalignment, inadequate/ineffective sleep, and loss of the environmental cues of a gravity environment. Complicating the psychological stressors are environmental factors; distracting background noise, unexpected and variable mission schedules, unfavorable thermal control, elevated CO2 levels, and an unusual sleep environment with schedules that impinge on pre‐sleep periods. Physiological contributors to poor sleep and fatigue include a cephalad fluid shift and back pain. Restful sleep is further challenged due to a lack of gravity‐related proprioceptive cues and need for restraints. The term "space fog" has been used by astronauts to describe a phenomenon of forgetfulness, slowed reaction time and transient confusion while trying to complete tasks. There is a distinct temporal correlation with arrival on the Space Station and the onset of slowed cognitive skills and a spontaneous resolution that may take up to 6 weeks. The Genesis of this phenomenon may be chronic fatigue secondary to transitioning from a planar environment to a 360deg microgravity perspective. Recently, countermeasures to improve sleep duration and quality in astronauts on the ISS have been instituted with moderate degrees of success as measured by self‐reaction time (psychomotor vigilance task testing), actigraphy, and subjective reports. Judicious use of stimulants and hypnotics, light therapy, controlled sleep periods and sleep shifting and reducing ambient CO2 levels are a few of the most promising countermeasures being used in space to improve sleep and reduce fatigue.

Scheuring, R. A.↗

NASA NTRS2015

High Intensity Resistive and Rowing Exercise Countermeasures Do Not Prevent Orthostatic Intolerance Following 70 Days of Bed Rest

More than 60% of US astronauts participating in Mir and early International Space Station missions (greater than 5 months) were unable to complete a 10‐min 80 deg head‐up tilt test on landing day. This high incidence of post‐spaceflight orthostatic intolerance may be related to limitations of the inflight exercise hardware that prevented high intensity training. PURPOSE: This study sought to determine if a countermeasure program that included intense lower‐body resistive and rowing exercises designed to prevent cardiovascular and musculoskeletal deconditioning during 70 days of 6 deg head-down tilt bed rest (BR), a spaceflight analog, also would protect against post‐ BR orthostatic intolerance. METHODS: Sixteen males participated in this study and performed no exercise (Control, n=10) or performed an intense supine exercise protocol with resistive and aerobic components (Exercise, n=6). On 3 days/week, exercise subjects performed lower body resistive exercise and a 30‐min continuous bout of rowing (greater than or equal to 75% max heart rate). On 3 other days/week, subjects performed only high‐intensity, interval‐style rowing. Orthostatic intolerance was assessed using a 15‐min 80 deg head‐up tilt test performed 2 days (BR‐2) before and on the last day of BR (BR70). Plasma volume was measured using a carbon monoxide rebreathing technique on BR‐3 and before rising on the first recovery day (BR+0). RESULTS: Following 70 days of BR, tilt tolerance time decreased significantly in both the Control (BR‐2: 15.0 +/- 0.0, BR70: 9.9 +/- 4.6 min, mean +/- SD) and Exercise (BR‐2: 12.2 +/- 4.7, BR70: 4.9 +/- 1.9 min) subjects, but the decreased tilt tolerance time was not different between groups (Control: ‐34 +/- 31, Exercise: ‐56 +/- 16%). Plasma volume also decreased (Control: ‐0.56 +/- 0.40, Exercise: ‐0.48 +/- 0.33 L) from pre to post‐BR, with no differences between groups (Control: ‐18 +/- 11%, Exerciser: ‐15 +/-1 0%). CONCLUSIONS: These findings confirm previous reports in shorter BR studies that the performance of an exercise countermeasure protocol by itself during BR does not prevent orthostatic intolerance or plasma volume loss. This suggests that protection against orthostatic intolerance in astronauts following long‐duration spaceflight will require an additional intervention, such as periodic orthostatic stress, fluid repletion, and/or lower‐body compression garments.

Lee, Stuart M. C.↗

NASA NTRS2015

Virtual Reality as a Medium for Sensorimotor Adaptation Training and Spaceflight Countermeasures

With the upcoming shift to extra‐long duration missions (1 year) aboard the ISS, sensorimotor adaptations during transitory periods in‐and‐out of microgravity are more important to understand and prepare for. Advances in virtual reality technology enables everyday adoption of these tools for entertainment and use in training. Experiencing virtual environments (VE) allows for the manipulation of visual flow to elicit automatic motor behavior and produce sensorimotor adaptation (SA). Recently, the ability to train individuals using repeatable and varied exposures to SA challenges has shown success by improving performance during exposure to a novel environment (Batson 2011). This capacity to 'learn to learn' is referred to as sensorimotor adaptive generalizability and, through the use of treadmill training, represents an untapped potential for individualized countermeasures. The goal of this study is to determine the feasibility of present head mounted displays (HMDs) to produce compelling visual flow information and the expected adaptations for use in future SA treadmill‐based countermeasures. Participants experience infinite hallways providing congruent (baseline) or incongruent visual information (half or double speed) via HMD while walking on an instrumented treadmill at 1.1m/s. As gait performance approaches baseline levels, an adaptation time constant is derived to establish individual time‐to‐adapt (TTA). It is hypothesized that decreasing the TTA through SA treadmill training will facilitate sensorimotor adaptation during gravitational transitions. In this way, HMD technology represents a novel platform for SA training using off‐the‐shelf consumer products for greater training flexibility in astronaut and terrestrial applications alike.

Madansingh, S.↗

NASA NTRS2016

Developing Personalized Sensorimotor Adaptability Countermeasures for Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. In this paper we will be presenting results from our ground-based study that show how behavioral, brain imaging and genomic data may be used to predict individual differences in sensorimotor adaptability to novel sensorimotor environments. This approach will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure, functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗

NASA NTRS2017

Designing for Reliability and Robustness in International Space Station Exercise Countermeasures Systems

As spaceflight durations have increased over the last four decades, the effects of microgravity on the human body have become far better understood, as have the exercise countermeasures. Through use of a combination of aerobic and resistive exercise devices, today's astronauts and cosmonauts are able to partially counter the losses in muscle strength, aerobic fitness, and bone strength that otherwise might occur during their missions on the International Space Station (ISS). Since 2000, the ISS has employed a variety of exercise equipment used as countermeasures to these risks. Providing reliable and available exercise systems has presented significant challenges due to the unique environment. In solving these, lessons have been learned that can inform development of future systems.

Moore, Cherice↗

NASA NTRS2017

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure.

Ebert, D.↗

NASA NTRS2017

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs and lower body negative pressure (LBNP) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure.

Ebert, Douglas↗

NASA NTRS2017

Zoledronate Prevents Simulated Weightlessness-Induced Bone Loss in the Cancellous Compartment While Blunting the Efficacy of a Mechanical Loading Countermeasure

Astronauts using high-force resistance training while weightless show a high-turnover remodeling state within the skeletal system, with resorption and formation biomarkers being elevated. One countermeasure for the skeletal health of astronauts includes an antiresorptive of the bisphosphonate (BP) drug class. We asked, does the combination of an anti-resorptive and high-force exercise during weightlessness have negative effects on bone remodeling and strength? In this study, we developed an integrated model to mimic the mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hind limb unloading (HU) to simulate weightlessness. We hypothesized that ZOL prevents structural degradation from simulated weightlessness and that CL and ZOL interact to render CL less effective. Thirty-two C57BL/6 mice (male, 16 weeks old, n=8/group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45μg/kg), or saline vehicle (VEH), prior to the start of HU. The right tibia was axially compressed in vivo 60x/day to 9N (+1200μstrain on the periosteal surface) and repeated 3x/week during HU. Left tibiae served as a within subject, non-compressed control. Ex vivo μCT was performed on all subjects to determine cancellous and cortical architectural parameters. Static and dynamic histomorphometry were carried out for the left and right tibiae to determine osteoclast- and osteoblast relevant surfaces. Further, micro damage was assessed in select groups by basic-fuchsin staining to test whether CL had an effect. For all assays, a multivariate (2x2x2) ANCOVA model was used to account for body weight changes. Additionally, for the tibiae, we incorporated a random effect for the subject (hence, a mixed model) to account for observations of both left and right tibiae within each subject. P < 0.05 was considered significant. In the cancellous compartment of the proximal tibial metaphysis, we observed a main effect from each independent variable, as determined by structural and histomorphometric assays. Specifically, as expected, ZOL showed an increase in the cancellous bone volume to total volume fraction (BV/TV, +32%) and trabecular number (+18%) compared to the VEH. As expected, ZOL decreased osteoclast surface (OC/BS) by -45% compared to VEH. Surprisingly, ZOL reduced mineralizing surface (MS/BS) and bone formation rate (BFR), indicators of osteoblast activity, by -40% and -54%, respectively, compared to VEH. Altogether, ZOL-treated mice displayed a low turnover state of remodeling in the metaphysis. In the context of skeletal aging, we speculate that ZOL prevented age-related cancellous strut loss during the experiment. As a main effect, as expected, HU decreased BV/TV by - 31% via reductions in both trabecular thickness (-11%) and number (-22%) compared to NA controls. Additionally, HU decreased MS/BS by -38% and bone formation rate (BFR) by -50% compared to NA controls. Altogether, these data are consistent with structural degradation resulting from imbalanced remodeling that favors resorption. As a main effect, CL increased BV/TV by +15% via increased trabecular thickness (+12%) compared to the noncompressed limb. As expected, CL increased MS/BS (+20%) and BFR (+24%), indicating osteoblast mineralization contributed to bone gains. These data show that CL provided an anabolic stimulus to the cancellous tissue. We observed unique interactions in ZOL*CL and HU*CL. First, ZOL prevented CL-induced increases in BV/TV and trabecular number, as compared to VEH. In the context of skeletal aging, these data suggest no added benefit from CL in the ZOL-treated mice. Interestingly, no microdamage was observed in mice that were unloaded and treated with ZOL (independent of CL). Secondly, HU prevented CL-induced increases in BFR, as compared to NA controls. These data suggest that either exercise is less effective or the kinetics of formation are slower during simulated weightlessness. Osteoclast surface was unchanged by either treatment. Thus, in contrast to exercising astronauts, these data do not suggest a high-turnover state in the metaphysis. To assess mechanical properties as a function of HU or ZOL, we tested the left femur in three-point bending ex vivo. As expected, HU decreased stiffness (-30%) compared to NA, and ZOL increased stiffness compared to VEH (+28%). Interestingly, HU increased the post-yield displacement, related to collagenous tensile loading, compared to NA (+20%). ZOL increased yield force (+11%) and ultimate force (+17%), which seems to explain the significant effect of ZOL increasing total energy (work-to-fracture, +15%), while not affecting the post yield displacement. Taken together, ZOL did not have detrimental affect on mechanical properties. Our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. We conclude that Zoledronate was an effective countermeasure against weightlessness-induced bone loss, though zoledronate, as well as weightlessness, rendered exercise-related mechanical loading less effective.

bone↗

NASA NTRS2023

Palmer Station, Antarctica: A Ground-Based Spaceflight Analog Suitable for Validation of Biomedical Countermeasures for Deep Space Missions

Astronauts are known to exhibit a variety of immunological alterations during spaceflight including changes in leukocyte distribution and plasma cytokine concentrations, a reduction in T-cell function, and subclinical reactivation of latent herpesviruses. These alterations are most likely due to mission-associated stressors including circadian misalignment, microgravity, isolation, altered nutrition, and increased exposure to cosmic radiation. Some of these stressors may also occur in terrestrial situations. This study sought to determine if crewmembers performing overwinter deployment at Palmer Station, Antarctica displayed similar immune alterations. The larger goal was to validate a ground analog suitable for the evaluation of countermeasures designed to protect astronauts during future deep space missions. For this pilot study, plasma, saliva, hair, and health surveys were collected from Palmer Station, Antarctica winterover participants at baseline, and at five overwinter timepoints. Twenty-six subjects consented to participate over the course of two seasons. Initial sample processing was performed at Palmer, and eventually stabilized samples were returned to the Johnson Space Center for analysis. A white blood cell differential was performed (real time) using a fingerstick blood sample to determine alterations in basic leukocyte subsets throughout the winterover. Plasma and saliva samples were analyzed for 30 and 13 cytokines, respectively. Saliva was analyzed for cortisol concentration and three latent herpesviruses (DNA by qPCR), EBV, HSV1, and VZV. Hair samples were analyzed for several hormones, as a measure of stress over prolonged periods of time. Voluntary surveys related to general health and adverse clinical events were distributed to participants. It is noteworthy that due to logistical constraints due to COVID-19, the baseline samples for each season were collected in Punta Arenas, Chile, after long international travel and during isolation. Therefore, the palmer pre mission samples may not reflect a true normal ‘baseline’. Minimal alterations were observed in leukocyte distribution during overwinter. The mean percentage of monocyte concentration elevated at one timepoint. Plasma G-CSF, IL1RA, MCP-1, MIP-1β, TNFα and VEGF were decreased during at least one overwinter timepoint, whereas RANTES was significantly increased. No statistically significant changes were observed in mean saliva cytokine concentrations. Salivary cortisol was substantially elevated throughout the entire winterover compared to baseline. Compared to shedding levels observed in healthy controls (23%), the percentage of participants who shed EBV was higher throughout all winterover timepoints (52-60%). Five subjects shed HSV1 during at least one timepoint throughout the season compared to no subjects shedding during pre-deployment. Finally, VZV reactivation, common in astronauts but exceptionally rare in ground-based stress analogs, was observed in one subject during pre-deployment and a different subject at WO2 and WO3. These pilot data, somewhat influenced by the COVID-19 situation, do suggest that participants at Palmer Station do undergo immunological alterations similar to, but likely in reduced magnitude, as those observed in astronauts. We suggest that overwinter at Palmer Station may be suitable test analog for spaceflight biomedical countermeasures designed to mitigate clinical risks for deep space missions.

Space↗