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All sourcesNASA NTRSDOE OSTI
NASA NTRS2015

Human Research Program Human Health Countermeasures Element: Evidence Report - Artificial Gravity

The most serious risks of long-duration flight involve radiation, behavioral stresses, and physiological deconditioning. Artificial gravity (AG), by substituting for the missing gravitational cues and loading in space, has the potential to mitigate the last of these risks by preventing the adaptive responses from occurring. The rotation of a Mars-bound spacecraft or an embarked human centrifuge offers significant promise as an effective, efficient multi-system countermeasure against the physiological deconditioning associated with prolonged weightlessness. Virtually all of the identified risks associated with bone loss, muscle weakening, cardiovascular deconditioning, and sensorimotor disturbances might be alleviated by the appropriate application of AG. However, experience with AG in space has been limited and a human-rated centrifuge is currently not available on board the ISS. A complete R&D program aimed at determining the requirements for gravity level, gravity gradient, rotation rate, frequency, and duration of AG exposure is warranted before making a decision for implementing AG in a human spacecraft.

Clement, Gilles↗
NASA NTRS2016

Management of Asymptomatic Renal Stones in Astronauts

Introduction: Management guidelines were created to screen and manage asymptomatic renal stones in U.S. astronauts. The risks for renal stone formation in astronauts due to bone loss and hypercalcuria are unknown. Astronauts have a stone risk which is about the same as commercial aviation pilots, which is about half that of the general population. However, proper management of this condition is still crucial to mitigate health and mission risks in the spaceflight environment. Methods: An extensive review of the literature and current aeromedical standards for the monitoring and management of renal stones was done. The NASA Flight Medicine Clinic's electronic medical record and Longitudinal Survey of Astronaut Health were also reviewed. Using this work, a screening and management algorithm was created that takes into consideration the unique operational environment of spaceflight. Results: Renal stone screening and management guidelines for astronauts were created based on accepted standards of care, with consideration to the environment of spaceflight. In the proposed algorithm, all astronauts will receive a yearly screening ultrasound for renal calcifications, or mineralized renal material (MRM). Any areas of MRM, 3 millimeters or larger, are considered a positive finding. Three millimeters approaches the detection limit of standard ultrasound, and several studies have shown that any stone that is 3 millimeters or less has an approximately 95 percent chance of spontaneous passage. For mission-assigned astronauts, any positive ultrasound study is followed by low-dose renal computed tomography (CT) scan, and flexible ureteroscopy if CT is positive. Other specific guidelines were also created. Discussion: The term "MRM" is used to account for small areas of calcification that may be outside the renal collecting system, and allows objectivity without otherwise constraining the diagnostic and treatment process for potentially very small calcifications of uncertain significance. However, a small asymptomatic MRM or stone within the renal collecting system may become symptomatic, and so affect launch and flight schedules, cause incapacitation during flight, and ultimately require medical evacuation. For exploration class missions, evacuation is unlikely. The new screening and management algorithm allows better management of mission risks, and will define the true incidence of renal stones in U.S. astronauts. This information will be used to refine future screening, countermeasures and treatment methods; and will also inform the needed capabilities to be flown on exploration-class missions.

Reyes, David↗
NASA NTRS2015

Does Simulated Spaceflight Modify Epigenetic Status During Bone Remodeling?

Little is known about the effects of spaceflight conditions on epigenetics. The term epigenetics describes changes to the genome that can affect expression of a gene without changes to the sequence of DNA. Epigenetic processes are thought to underlie cellular differentiation, where transcription of specific genes occurs in response to key stimuli, and may be heritable - passing from one cell to its daughter cell. We hypothesize that the mechanical environment during spaceflight, namely microgravity-induced weightlessness or exercise regulate gene expression in the osteoblast-lineage cells both to control bone formation by osteoblasts and bone resorption by osteoclasts, which continually shapes bone structure throughout life. Similarly we intend to evaluate how radiation regulates these same bone cell activity and differentiation related genes. We further hypothesize that the regulation in bone cell gene expression is at least partially controlled through epigenetic mechanisms of methylation or small non-coding RNA (microRNAs). We have acquired preliminary data suggesting that global genome methylation is modified in response to axial compression of the tibia - a model of exercise. We intend to pursue these hypotheses wherein we will evaluate changes in gene expression and, congruently, changes in epigenetic state in bones from mice subjected to the aforementioned conditions: hindlimb unloading to simulate weightlessness, axial compression of the tibia, or radiation exposure in order to gain insight into the role of epigenetics in spaceflight-induced bone loss.

radiation↗
NASA NTRS2016

Management of Asymptomatic Renal Stones in Astronauts

Introduction: Management guidelines were created to screen and manage asymptomatic renal stones in U.S. astronauts. The risks for renal stone formation in astronauts due to bone loss and hypercalcuria are unknown. Astronauts have a stone risk which is about the same as commercial aviation pilots, which is about half that of the general population. However, proper management of this condition is still crucial to mitigate health and mission risks in the spaceflight environment. Methods: An extensive review of the literature and current aeromedical standards for the monitoring and management of renal stones was done. The NASA Flight Medicine Clinic's electronic medical record and Longitudinal Survey of Astronaut Health were also reviewed. Using this work, a screening and management algorithm was created that takes into consideration the unique operational environment of spaceflight. Results: Renal stone screening and management guidelines for astronauts were created based on accepted standards of care, with consideration to the environment of spaceflight. In the proposed algorithm, all astronauts will receive a yearly screening ultrasound for renal calcifications, or mineralized renal material (MRM). Any areas of MRM, 3 millimeters or larger, are considered a positive finding. Three millimeters approaches the detection limit of standard ultrasound, and several studies have shown that any stone that is 3 millimeters or less has an approximately 95 percent chance of spontaneous passage. For mission-assigned astronauts, any positive ultrasound study is followed by low-dose renal computed tomography (CT) scan, and flexible ureteroscopy if CT is positive. Other specific guidelines were also created. Discussion: The term "MRM" is used to account for small areas of calcification that may be outside the renal collecting system, and allows objectivity without otherwise constraining the diagnostic and treatment process for potentially very small calcifications of uncertain significance. However, a small asymptomatic MRM or stone within the renal collecting system may become symptomatic, and so affect launch and flight schedules, cause incapacitation during flight, and ultimately require medical evacuation. For exploration class missions, evacuation is unlikely. The new screening and management algorithm allows better management of mission risks, and will define the true incidence of renal stones in U.S. astronauts. This information will be used to refine future screening, countermeasures and treatment methods; and will also inform the needed capabilities to be flown on exploration-class missions.

Reyes, David↗
NASA NTRS2016

The Use of Microgravity Simulators for Space Research

The spaceflight environment is known to influence biological processes ranging from stimulation of cellular metabolism to possible impacts on cellular damage repair, suppression of immune functions, and bone loss in astronauts. Microgravity is one of the most significant stress factors experienced by living organisms during spaceflight, and therefore, understanding cellular responses to altered gravity at the physiological and molecular level is critical for expanding our knowledge of life in space. Since opportunities to conduct experiments in space are scarce, various microgravity simulators and analogues have been widely used in space biology ground studies. Even though simulated microgravity conditions have produced some, but not all of the biological effects observed in the true microgravity environment, they provide test beds that are effective, affordable, and readily available to facilitate microgravity research. A Micro-g Simulator Center is being developed at Kennedy Space Center (KSC) to offer a variety of microgravity simulators and platforms for Space Biology investigators. Assistance will be provided by both KSC and external experts in molecular biology, microgravity simulation, and engineering. Comparisons between the physical differences in microgravity simulators, examples of experiments using the simulators, and scientific questions regarding the use of microgravity simulators will be discussed.

Simulation↗
NASA NTRS2016

Skeletal Micro-RNA Responses to Simulated Weightlessness

Astronauts lose bone structure during long-duration spaceflight. These changes are due, in part, to insufficient bone formation by the osteoblast cells. Little is known about the role that small (approximately 22 nucleotides), non-coding micro-RNAs (miRNAs) play in the osteoblast response to microgravity. We hypothesize that osteoblast-lineage cells alter their miRNA status during microgravity exposure, contributing to impaired bone formation during weightlessness. To simulate weightlessness, female mice (C57BL/6, Charles River, 10 weeks of age, n = 7) were hindlimb unloaded up to 12 days. Age-matched and normally ambulating mice served as controls (n=7). To assess the expression of miRNAs in skeletal tissue, the tibia was collected ex vivo and cleaned of soft-tissue and marrow. Total RNA was collected from tibial bone and relative abundance was measured for miRNAs of interest using quantitative real time PCR array looking at 372 unique and well-characterized mature miRNAs using the delta-delta Ct method. Transcripts of interest were normalized to an average of 6 reference RNAs. Preliminary results show that hindlimb unloading decreased the expression of 14 miRNAs to less than 0.5 times that of the control levels and increased the expression of 5 miRNAs relative to the control mice between 1.2-1.5-fold (p less than 0.05, respectively). Using the miRSystem we assessed overlapping target genes predicted to be regulated by multiple members of the 19 differentially expressed miRNAs as well as in silico predicted targets of our individual miRNAs. Our miRsystem results indicated that a number of our differentially expressed miRNAs were regulators of genes related to the Wnt-Beta Catenin pathway-a known regulator of bone health-and, interestingly, the estrogen-mediated cell-cycle regulation pathway, which may indicate that simulated weightlessness modulated systemic hormonal levels or hormonal transduction that additionally contributed to bone loss. We plan to follow up these findings by measuring gene expression of miRNA-regulated genes within these two pathways with the aim of furthering our understanding of the function of miRNAs in the skeletal response to spaceflight.

musculoskeletal system↗
NASA NTRS2016

Risky Business: The Science and Art of Radiation Risk Communication in the High Risk Context of Space Travel

Successfully communicating the complex risks associated with radiation exposure is a difficult undertaking; communicating those risks within the high-risk context of space travel is uniquely challenging. Since the potential risks of space radiation exposure are not expected to be realized until much later in life, it is hard to draw comparisons between other spaceflight risks such as hypoxia and microgravity-induced bone loss. Additionally, unlike other spaceflight risks, there is currently no established mechanism to mitigate the risks of incurred radiation exposure such as carcinogenesis. Despite these challenges, it is the duty of the Space Radiation Analysis Group (SRAG) at NASA's Johnson Space Center to provide astronauts with the appropriate information to effectively convey the risks associated with exposure to the space radiation environment. To this end, astronauts and their flight surgeons are provided with an annual radiation risk report documenting the astronaut's individual radiation exposures from space travel, medical, and internal radiological procedures throughout the astronaut's career. In an effort to improve this communication and education tool, this paper critically reviews the current report style and explores alternative report styles to define best methods to appropriately communicate risk to astronauts, flight surgeons, and management.

Elgart, Shona Robin↗
NASA NTRS2016

Simulated Space Radiation: Murine Skeletal Responses During Recovery and with Mechanical Stimulation

Simulated space radiation at doses similar to those of solar particle events or a round-trip sojourn to Mars (1-2Gy) may cause skeletal tissue degradation and deplete stem/progenitor cell pools throughout the body. We hypothesized that simulated space radiation (SSR) causes late, time-dependent deficits in bone structure and bone cell function reflected by changes in gene expression in response to anabolic stimuli. We used a unique sequential dual ion exposure (proton and iron) for SSR to investigate time-dependence of responses in gene expression, cell function, and microarchitecture with respect to radiation and an anabolic stimulus of axial loading (AL). Male 16-wk C57BL6/J mice (n=120 total) were exposed to 0Gy (Sham, n=10), 56Fe (2Gy, positive control dose, n=10), or sequential ions for SSR (1Gy 1H/56Fe/1H, n=10) by total body irradiation (IR), and the tissues were harvested 2 or 6 mo. later. Further, to assess the response to anabolic stimuli, we subjected additional Sham-AL (n=15) and SSR-AL (n=15) groups to rest-inserted tibial axial loading (AL) starting at 1 and 5 months post-IR (-9N, 60 cycles/day, 3 days/wk, 4 wks). Exposure to 56Fe caused a significant reduction in cancellous bone volume fraction (BV/TV) compared to Sham (-34%) and SSR (-20%) in the proximal tibia metaphysis at 2-months post-IR; however BV/TV for SSR group was not different than Sham. Both 56Fe and SSR caused significant reduction in trabecular number (Tb.N) compared to Sham (-33% and -16%, respectively). Further, Tb.N for 56Fe (2Gy) was significantly lower than SSR (-21%). Ex vivo culture of marrow cells to assess growth and differentiation of osteoblast lineage cells 6 months post-IR showed that both 56Fe and SSR exposures significantly impaired colony formation compared to Sham (-66% and -54%, respectively), as well as nodule mineralization (-90% and -51%, respectively). Two-way analysis of variance showed that both mechanical loading and radiation reduced BV/TV, mechanical loading reduced trabecular thickness (Tb.Th), and radiation reduced Tb.N, at both time points. To assess acute response to mechanical stimuli, samples were harvested from a subset of Sham-AL (n=5) and SSR-AL (n=5) to measure changes in gene expression levels. Preliminary results indicate that axial loading increased expression of the antioxidant response gene Nfe2l2 and the osteoprogenitor-associated marker Runx2 in the bone marrow cells, and there was an interaction effect between axial loading and radiation at 2-months post-IR. Additional analyses of gene expression levels in the mineralized tissue are in progress. Results indicate that SSR caused persistent impairment of osteoblast colony formation and nodule mineralization 6-mo post-IR. Contrary to our hypothesis, simulated space radiation did not impair the ability of cancellous bone to respond to a mechanical anabolic stimulus, consistent with our previous findings. Hence, compressive loading may be a potential countermeasure against spaceflight-induced bone loss.

MURINE SKELETAL↗
NASA NTRS2016

Exercise Equipment: Neutral Buoyancy

Load Bearing Equipment for Neutral Buoyancy (LBE-NB) is an exercise frame that holds two exercising subjects in position as they apply counter forces to each other for lower extremity and spine loading resistance exercises. Resistance exercise prevents bone loss on ISS, but the ISS equipment is too massive for use in exploration craft. Integrating the human into the load directing, load generating, and motion control functions of the exercise equipment generates safe exercise loads with less equipment mass and volume.

Shackelford, Linda↗
NASA NTRS2016

The Use of Microgravity Simulators for Space Research

The spaceflight environment is known to influence biological processes ranging from stimulation of cellular metabolism to possible impacts on cellular damage repair, suppression of immune functions, and bone loss in astronauts. Microgravity is one of the most significant stress factors experienced by living organisms during spaceflight, and therefore, understanding cellular responses to altered gravity at the physiological and molecular level is critical for expanding our knowledge of life in space. Since opportunities to conduct experiments in space are scarce, various microgravity simulators and analogues have been widely used in space biology ground studies. Even though simulated microgravity conditions have produced some, but not all of the biological effects observed in the true microgravity environment, they provide test beds that are effective, affordable, and readily available to facilitate microgravity research. Kennedy Space Center (KSC) provides ground microgravity simulator support to offer a variety of microgravity simulators and platforms for Space Biology investigators. Assistance will be provided by both KSC and external experts in molecular biology, microgravity simulation, and engineering. Comparisons between the physical differences in microgravity simulators, examples of experiments using the simulators, and scientific questions regarding the use of microgravity simulators will be discussed.

Simulation↗
NASA NTRS2017

Space Pomology: Dwarf Plums for Fresh Food Production

Recently, USDA ARS researchers genetically modified plums for rapid breeding work and noticed the plants could flower and develop fruit rapidly on relatively small plants. We have tested several of these genetically modified (GM) plums in plant chambers to assess their potential as a space crop. We have been able to clone these genetic lines using cuttings that are rooted using growth regulating compounds. Results showed that the GM plums indeed flower and fruit on small plants in controlled environments similar to what might be used in space, but they require cross-pollination with pollen from a standard plum. Analysis of stomatal conductance and leaf transpiration showed that water use went up in the light period, as expected, and but that GM types typically showed higher conductance than a standard plum. Analysis of tissue showed that fruit could be a good source of potassium and phenolic compounds, which could be beneficial as a bone loss countermeasure (Smith et al., 2014). These findings are all promising for using dwarf GM plums as a supplemental food for space, but further horticultural testing is needed before they are ready.

Life Support↗
NASA NTRS2017

Characterizing Fractures Across the Astronaut Corps: Preliminary Findings from Population-Level Analysis

Despite evidence of bone loss during spaceflight and the implementation of countermeasures to mitigate this loss, the subsequent risk of fracture among astronauts is not known. Multiple factors such as age, sex, fracture history, and others may combine to increase fracture risk. The purpose of this study was to describe fractures among the astronaut population and generate questions for future occupational surveillance studies.

Rossi, Meredith M.↗
NASA NTRS2017

Preventing Precipitation in the ISS Urine Processor

The ISS Urine Processor Assembly (UPA) was initially designed to achieve 85% recovery of water from pretreated urine on ISS. Pretreated urine is comprised of crew urine treated with flush water, an oxidant (chromium trioxide), and an inorganic acid (sulfuric acid) to control microbial growth and inhibit precipitation. Unfortunately, initial operation of the UPA on ISS resulted in the precipitation of calcium sulfate at 85% recovery. This occurred because the calcium concentration in the crew urine was elevated in microgravity due to bone loss. The higher calcium concentration precipitated with sulfate from the pretreatment acid, resulting in a failure of the UPA due to the accumulation of solids in the Distillation Assembly. Since this failure, the UPA has been limited to a reduced recovery of water from urine to prevent calcium sulfate from reaching the solubility limit. NASA personnel have worked to identify a solution that would allow the UPA to return to a nominal recovery rate of 85%. This effort has culminated with the development of a pretreatment based on phosphoric acid instead of sulfuric acid. By eliminating the sulfate associated with the pretreatment, the brine can be concentrated to a much higher concentration before calcium sulfate reach the solubility limit. This paper summarizes the development of this pretreatment and the testing performed to verify its implementation on ISS.

Muirhead, Dean↗
NASA NTRS2017

New Developments in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space

Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASA's life sciences research to perform long duration, rodent experiments on the International Space Station (ISS) to study effects of the space environment on the musculoskeletal and neurological systems of mice as model organisms of human health and disease, particularly in areas of muscle atrophy, bone loss, and fracture healing. To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research Project at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. The Rodent Research Habitat provides a living environment for animals on ISS according to standard animal welfare requirements, and daily health checks can be performed using the habitats camera system. Results from these studies contribute to the science community via both the primary investigation and banked samples that are shared in publicly available data repository such as GeneLab. Following each flight, through the Biospecimen Sharing Program (BSP), numerous tissues and thousands of samples will be harvested, and distributed from the Space Life and Physical Sciences (SLPS) to Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). Every completed mission sets a foundation to build and design greater complexity into future research and answer questions about common human diseases. Together, the hardware improvements (enrichment, telemetry sensors, cameras), new capabilities (live animal return), and experience that the Rodent Research team has gained working with principal investigator teams and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical research objectives.

Shirazi, Yasaman↗
NASA NTRS2018

Dried Plum as a Candidate Radiomitigant

This presentation will focus on data obtained from that authors' studies that test the efficacy of dried plum as a countermeasure against radiation-induced bone loss.

Schreurs, Ann-Sofie↗
NASA NTRS2018

Design and Development of Modules to Support Live Microscopic Imaging on Ground-Based Microgravity Simulators

In space, astronauts are exposed to environmental stressors that often result in physiological changes. One prominent stressor in spaceflight is microgravity, and research has shown that long term microgravity exposure causes muscle atrophy, bone loss, cardiovascular concerns, and vision impairment. It is critical to understand how altered gravity affects physiology on the cellular, molecular, and gene level in order to accurately assess health risks and to develop effective countermeasures. Ground-based microgravity simulators such as random positioning machines (RPMs) are used to produce some of the biological effects of altered gravity on different cell types and organisms. Real-time imaging during simulations are of particular interest as we can study how basic cell functions such as cell division, cell migration, and proliferation progress under microgravity conditions. However, design limitations of present microgravity simulators such as susceptibility to parasitic vibration and displacement of the sample from the center of rotation challenge the accuracy of experiment results and live images. We have developed a cell culture sample holder module suitable for live microscopic imaging on an RPM. CAD modeling and 3D printing technology were used to implement modifications to the sample holder and to install a digital microscope to perform live bright-field and fluorescent imaging. Vibration damping materials were also investigated to allow for stable imaging while the microgravity simulator was within a cell culture incubator. Novel methods and hardware modifications for improving live cell imaging on ground-based microgravity simulators were proposed and discussed.

3D printing↗
NASA NTRS2018

Biomedical Science and Technology on the International Space Station - Benefits for Humanity (Ciencia Y Tecnologia Biomedica En La Estacion Espacial Internacional - Beneficios Para La Humanidad)

The International Space Station is a unique laboratory for performing investigations that affect human health both in space and on Earth. During its time in orbit, the space station has enabled research that is providing a better understanding of many aspects of human health including aging, trauma, disease and environmental impacts. Driven by the need to support astronaut health, several biological and human physiological investigations have yielded important results that we on Earth can also benefit from. These results include new ways to mitigate bone loss, insights into bacterial behavior, and innovative wound-healing techniques. Advances in telemedicine, disease models, psychological stress response systems, nutrition and cell behavior are just a few more examples of the benefits that have been gained from applying studies in orbit to human health back on Earth.

Love, John E.↗
NASA NTRS2016

Synthetic Biologic Membrane

The International Space Station (ISS) is a test bed for the technologies that will be used to travel to Mars and beyond. The lessons learned from operating the ISS provide valuable direction to future research and technology development programs. One of the most critical and complicated subsystems on ISS is the life support system. The life support system keeps the crew alive by recycling both air and water. The ISS water recycling system has been operating since 2009 and one of the main lessons learned is that reliability is a key technology performance metric. In the long run reliability is a key cost driver and is a critical factor in insuring crew safety. For long duration missions such as the exploration of Mars, where resupply of spare parts from Earth is difficult if not impossible, reliability is even more important. This presentation will cover research into improving the reliability of ISS systems. It will discuss research into the development of a biomimetic membrane materials that provides self-regeneration capabilities for water recycling systems. It will also cover research into past failures of the ISS water recycling system caused by astronaut bone loss and the build-up of trace contaminates in the cabin.

Biology↗