NASA Human Research Program Research Articles

Daily use of veno-constrictive thigh cuffs during 30 days of strict 6° head-down tilt bedrest to reverse the headward fluid shift

Introduction: Chronic exposure to weightlessness induces a persistent headward fluid shift, which may contribute to the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). Strict 6° head-down tilt bedrest (HDTBR) is a spaceflight analog that induces a headward fluid shift and development of SANS findings, enabling the evaluation of potential countermeasures. Lower body exercise can induce a sustained post-exercise hyperemia thereby shifting blood away from the central circulation. In addition, veno-constrictive thigh cuffs (VTC) can sequester blood volume in the legs. The purpose of this study was to determine whether 6 hours of daily VTC use following cycling exercise (Ex+VTC) could reverse the headward fluid shift during 30 days of strict 6° HDTBR. We hypothesized that Ex+VTC would sequester fluid in the legs leading to increased thigh circumference and reduced stroke volume (SV), cardiac output (CO), internal jugular vein (IJV) cross-sectional area (CSA) and pressure, and intraocular pressure (IOP). Methods: Participants were randomly assigned to a Control (n=12, 6 female) or Ex+VTC (n=12, 4 female) group and completed baseline data collection (BDC) in the seated and supine posture followed by 30 days of strict 6° HDTBR. The Ex+VTC group completed a maximal exercise test on a cycle ergometer in 6° HDT posture during BDC to establish work rates during HDTBR. The Ex+VTC group performed 10 minutes of light cycle exercise, cycled for 45 minutes at 45% of their max wattage, and then donned VTC to ~50 mmHg for 6 hours on 6 of 7 days per week during HDTBR. Data were collected before exercise and 30 minutes and 6 hours after exercise and donning VTCs on days 3, 17, and 29 of HDTBR. Controls were studied at similar time points. Days were nested within the models. Mixed models were used to determine differences between groups in the change in thigh circumference measured using a flexible tape measure, bilateral IOP measured using tonometry, CO measured using the inert gas rebreathe technique (Innocor), and ultrasound of bilateral IJV CSA and pressure from before to 30 min and 6 hours after use of the countermeasure. Left and right IJV and IOP data were nested within each participant. Results: The Ex+VTC group completed all exercise sessions followed by 6 hours of VTC use. Compared to Control, thigh circumference was greater after 30 minutes (+1.3 vs. -0.2 cm, p<0.001) and 6 hours of VTC use (+2.5 cm vs. -0.1 cm in controls, p<0.001). SV (-38 vs. 2 ml, p<0.001) and CO (-1.5 vs. 0.3 L/min, p<0.001) were reduced at 30 minutes and 6 hours of VTC use (SV: -30 vs. 5 ml, p<0.001; CO: -1.1 vs. 0.6 L/min, p<0.001) compared to Control. IJV CSA and pressure were reduced at 30 minutes (CSA, p<0.001; pressure, p=0.001) and 6 hours of VTC use (CSA, p<0.001; pressure, p=0.007). IOP was not different compared to Control. Conclusions:Use of VTC for 6 hours after 45 minutes of exercise successfully sequestered fluid in the legs, leading to a reduction in central blood volume, IJV CSA, and IJV pressure. Thus, an Ex+VTC countermeasure resulted in a partial fluid shift reversal. This research was supported by the NASA Human Research Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Circuits and Biomarkers of the Central Nervous System Relating to Astronaut Performance: Summary Report for a NASA-Sponsored Technical Interchange Meeting.

Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow for translational studies between species. Three discussion groups were directed to use operationally relevant performance tasks as a driver when identifying biomarkers and brain regions or circuits for selected constructs. Here we summarize small-group discussions in tables of circuits and biomarkers categorized by (a) sensorimotor, (b) behavioral medicine and (c) integrated approaches (e.g., physiological responses). In total, hundreds of biomarkers have been identified and are summarized herein by the respective group leads. We hope the meeting proceedings become a rich resource for NASA's Human Research Program (HRP) and the community of researchers.

0287 Humans are capable of achieving sufficient sleep in microgravity

Abstract Introduction Studies consistently find that humans average approximately six hours of sleep per night in space, which is less than they sleep on Earth. It is unclear whether the sleep loss observed during spaceflight is related to modifiable factors, such as irregular scheduling and inadequate sleep environment or due to features of spaceflight that may alter physiology, such as microgravity. Recent missions have afforded crew better, more stable sleep schedules, and an improved sleep environment. Hence, the evaluation of sleep under these improved conditions should provide insight into the causes of sleep deficiency observed in space thus far. Methods Crewmembers (n = 19) wore actiwatches for two bouts of data collection lasting two weeks each before flight (at approximately L-270 and L-180), either continuously (n = 9) or for two weeks every two months while in space (n = 10), and for seven days postflight, immediately upon return to Earth. We compared sleep outcomes (sleep duration, wake after sleep onset [WASO], sleep efficiency, and sleep latency) between phases of flight using mixed effects models, with participant and intercept included as a random effect. Results Crewmembers averaged 7.3 +/- 0.4 hours of sleep per night in space. Though this was less than they achieved preflight (7.9 +/- 0.5) or postflight (7.8 +/- 0.8; F (2, 2866) = 86.26, p < .0001, ηp2 = .06), this duration of sleep meets the recommended amount for optimal human health and well-being. Sleep efficiency (%) also increased inflight (88.7 +/- 2.7) compared to preflight (84.7 +/- 5.5) and postflight (84.4 +/- 6.1; F (2, 2630) = 124.08, p < .0001, ηp2 = .09), while WASO (min) decreased inflight (29.6 +/- 8.2) compared to preflight (46.4 +/- 15.5) and postflight (48.7 +/- 16.0); F (2, 2629) = 285.90, p < .0001, ηp2 = .18). There were no changes across these variables over time inflight. Conclusion We conclude that humans are capable of achieving sufficient sleep in space. Going forward, it is imperative that crewmembers are provided with stable schedules, with moderate workload, and environments that are conducive to sleep. Support (if any) NASA Human Factors and Behavioral Health Element, NASA Human Research Program

Future Health: Leveraging Space for Health Innovation

Mr. James Hury, Deputy Director and Chief Innovation Officer for the Translational Research Institute for Space Health (TRISH) explores the future of health, and how preparing technologies to protect the health of astronauts in deep space can advance health for all humans, wherever they explore. Supported by the NASA Human Research Program (HRP), TRISH is an applied space health research catalyst that funds disruptive, high-impact scientific studies and technologies to equip astronauts for deep space exploration. The institute is seeking bold, courageous proposals from experts in disciplines spanning medicine, science, technology, and engineering who have the ideas and skills that will help us find solutions for the challenges and limitations facing human space travel.

Enabling Human Space Exploration Missions Through Progressively Earth Independent Medical Operations (EIMO).

Goal: Current Space Medicine operations depend on terrestrial support to manage medical events. As astronauts travel to destinations such as the Moon, Mars, and beyond, distance will substantially limit this support and require increasing medical autonomy from the crew. This paper defines Earth Independent Medical Operations (EIMO) and identifies key elements of a conceptual EIMO system. Methods: The NASA Human Research Program Exploration Medical Capability Element held a 2-day conference at Johnson Space Center in Houston, TX with NASA experts representing all aspects of Space Medicine. Results: EIMO will be a process enabling progressively resilient deep space exploration systems and crews to reduce risk and increase mission success. Terrestrial assets will continue to provide pre-mission screening, planning, health maintenance, and prevention, while onboard medical care will increasingly be the purview of the crew. Conclusions: This paper defines and describes the key components of EIMO.

Bone Metabolism During Strict Head-Down Tilt Bed Rest and CO2 Exposure

ObjectivesCarbon dioxide (CO2) levels on board the International Space Station reach 10× those of outdoor terrestrial levels. We report here studies assessing whether increased levels of ambient CO2 contribute to elevated bone resorption characteristically observed with bed rest as an analog for skeletal unloading during spaceflight.MethodsData are reported from two ground-based studies which included 12 male and 7 female subjects placed in a strict −6° head-down tilt (HDT) position for 30 days at 0.5% ambient CO2 or 60 days with nominal environment (0.04% CO2). Subjects were neither afforded a pillow nor allowed to use an elbow while eating to increase headward fluid pressure. Bone mineral density (BMD) and bone mineral content (BMC) were measured with dual-energy X-ray absorptiometry. Blood and urine were collected before and during HDT for analysis.ResultsThere was no change in BMD or BMC. Excretion of collagen crosslinks increased during HDT (p < 0.001) with no additive effect of CO2. Serum and urine mineral concentrations were not affected by CO2. Serum PTH and 1,25-deoxyhydroxyvitamin D were both reduced during bed rest (p < 0.0001), likely secondary to calcium efflux from bone, but with no additive effect of CO2 exposure. These changes reinforce the impact of decreased mechanical loading on bone and mineral homeostasis and the efficacy of the strict HDT model.ConclusionsExposure to 0.5% CO2 for 30 days did not exacerbate bone resorption during strict HDT bed rest. Future research on bone metabolism at varied CO2 levels is needed to clarify a risk ceiling for bone resorption, especially as missions progress beyond low-Earth orbit.Funding SourcesThe data reported here were from the NASA Human Research Program Standard Measures Cross-Cutting Project. Funding was provided by the NASA Human Research Program's Human Health Countermeasures Element. ERM was funded through a NASA Summer Science Institute Fellowship.

Nutrition and Human Space Flight: Evidence From 4–6 Month Missions to the International Space Station

Objectives2020 marked the 20th anniversary of a continuous human presence off the planet. Space flight is challenging, with environmental stressors, a closed food system, and adaptations affecting virtually all body systems. Our objective was to evaluate the time course of biochemical changes during flight, the effects of countermeasures, and the relationship between diet and physiological outcomes. MethodsBlood and urine samples were collected before, during, and after flight from 65 astronauts. These were analyzed for a broad-based survey of physiological systems. Detailed diet records were available from 27 astronauts using an iPad App designed for use on ISS. ResultsThe average intake of fruits and vegetables was lower than recommended (2.6 ± 0.9 servings per day), but intakes correlated with outcomes at landing. Specifically, higher intakes were positively correlated with vitamin C status (R2 = 0.43, P < 0.05), and negatively correlated with inflammation (Interferon-γ, R2 = 0.76, P = 0.001) and oxidative stress (malondialdehyde, R2 = 0.51, P < 0.05). Despite limited dietary sources and no UV light exposure, 800 IU vitamin D/d supplements maintained vitamin D status (serum 25OH-vitamin D was 78 ± 4 nmol/L during flight). Cholesterol (298 ± 163 mg/d) and saturated fat (26.1 ± 11 g/d, 10.4 ± 3.1% of kcals) intakes were associated with a 10% and 14% increase in circulating total and LDL cholesterol, respectively (P < 0.001). Perhaps the most notable finding is that one-carbon biochemistry is altered in astronauts who experienced ophthalmic changes during and after flight, where circulating homocysteine concentrations were higher in affected astronauts compared to unaffected astronauts (P < 0.001), and these differences existed before flight. ConclusionsEvaluation of countermeasure effectiveness and individual and group responses to spaceflight will continue to be important on the ISS and will inform future space programs including Artemis and Gateway missions to the moon. Those efforts will require similar types of comprehensive assessments to allow the next steps in human exploration of space. By uniting nutrition with other disciplines, the importance of diet in heath can be further enlightened, with potential implications for both space explorers and for those remaining on Earth. Funding SourcesThis research was funded by the NASA Human Research Program and DLR.

133 The Effects of Chronic Sleep Restriction on Human Oculomotor Behavior

Abstract Introduction Oculomotor behavioral metrics change according to time awake and circadian phase following a distinct pattern of impairment. Acute sleep deprivation (ASD) causes large decreases in pursuit initiation and steady-state gain, and a compensatory increase in saccadic rate without any systematic change in saccadic size. It also causes large deficits in visual processing of direction and speed, and impaired saccade dynamics. Such deterioration likely reflects changes in both higher cortical and brainstem function, explaining in-part how sleep loss and circadian misalignment affect cognition. It is unclear how oculomotor behavior might change according to chronic sleep restriction (CSR). Here, we measured the same eye-movement metrics during CSR. Methods Twelve healthy participants (6 females) kept a fixed wake-time sleep-wake schedule, at home for four weeks (weeks 1 and 3 = 9h time in bed (TIB); weeks 2 and 4 randomized to 5h or 9h TIB; actigraphy confirmed). Following weeks two and four, participants completed a 13-hour laboratory visit under dim light (&amp;lt;15 lux), where they maintained a semi-recumbent posture and were provided with hourly isocaloric snacks. A visual tracking task was performed hourly to assess pursuit and saccadic responses and visual motion processing. Performance metrics were computed using MATLAB, including pursuit gain (eye speed/target speed), the rate and amplitude of catch-up saccades, and the accuracy and precision of direction and speed processing. Results As expected, we found a small but significant (t(11)=-2.17, p&amp;lt;0.03) reduction in pursuit gain (mean+/-SEM: -0.028 +/-0.013 with a large (t(11)=2.96, p&amp;lt;0.01) increase in saccadic rate (0.37 +/-0.13 Hz). However, surprisingly, we found a significant (t(11)=-2.52, p&amp;lt;0.03) decrease in the amplitude of catch-up saccades (-0.15 +/-0.06 deg). The only systematic alteration to visual motion processing was a small reduction in horizontal-vertical asymmetry, which was previously observed with ASD. Conclusion A week of CSR to 5h is associated with only mild impairment in smooth pursuit eye movements with little impact on visual motion processing. However, CSR caused a maladaptive decrease in saccade amplitude that was not observed during ASD. Eye-movement metrics reveal differential neurological effects of CSR versus ASD. Support (if any) Force Health Protection Program, ONR (SAA2402925-1), NASA Human Research Program, and agreement NNX17AE07A

Nutrition and Human Space Flight: Evidence from 4–6 Month Missions to the International Space Station

Abstract Objectives 2020 marks the 20th anniversary of a continuous human presence off the planet. Space flight is physically and physiologically challenging, with environmental stressors, a closed food system, and adaptations affecting virtually all body systems. Key objectives for this effort included evaluating the time course of biochemical changes that occur during flight, the effects of exercise countermeasures, and the relationship between dietary intake and physiological outcomes. Methods Blood and urine samples were collected before, during, and after flight from 65 astronauts. These were analyzed for a broad-based survey of physiological systems. Detailed diet records were available from 27 astronauts using an iPad App designed for use on ISS. Results The average intake of fruits and vegetables was lower than recommended (2.6 ± 0.9 servings per day), but intakes correlated with outcomes at landing. Specifically, higher intakes were positively correlated with vitamin C status (R2 = 0.43, P &amp;lt; 0.05), and negatively correlated with inflammation (Interferon-γ, R2 = 0.76, P = 0.001) and oxidative stress (malondialdehyde, R2 = 0.51, P &amp;lt; 0.05). Despite limited dietary sources and no UV light exposure, supplementing with 800 IU vitamin D/day maintained vitamin D status (serum 25OH-vitamin D was 78 ± 4 nmol/L during flight). Cholesterol (298 ± 163 mg/d) and saturated fat (26.1 ± 11 g/d, 10.4 ± 3.1% of kcals) intakes were associated with a 10% and 14% increase in circulating total and LDL cholesterol concentrations, respectively (P &amp;lt; 0.001). Perhaps the most notable finding is evidence that one-carbon biochemistry is altered in astronauts who experienced ophthalmic changes during and after flight, where circulating homocysteine concentrations were higher in affected astronauts compared to unaffected astronauts (P &amp;lt; 0.001), and these differences existed before flight. Conclusions Evaluation of countermeasure effectiveness and individual and group responses to spaceflight will continue to be important on the ISS, and will inform future space programs including Artemis and Gateway missions to the moon. Those efforts will require similar types of comprehensive assessments to allow the next steps in human exploration of space. By uniting nutrition with other disciplines, the importance of diet in heath can be further enlightened, with potential implications for both space explorers and for those remaining on Earth. Funding Sources This research was funded by the NASA Human Research Program and DLR.

Capability considerations for enhancing safety on long duration crewed missions: Insights from a technical interchange meeting on autonomous crew operations

As future flight crews on long duration deep space missions are expected to operate more autonomously, considerations must be given to onboard capabilities and human-computer teaming that will fortify the safety net traditionally provided by the Mission Control Center. In August 2018, the Human Factors and Behavioral Performance Element of NASA's Human Research Program convened a Technical Interchange Meeting (TIM) on Autonomous Crew Operations at NASA Ames Research Center to address how intelligent technologies can be utlilzed to augment crew capabilities to support real-time anomaly response. In this paper, we highlight three topic areas discussed at the TIM that have direct implications for future crew anomaly response capabilities: smart structures, cognitive assistants, and manpower.

MTRR 66 and SHMT1 1420 Variants Are Associated with Optic Disc Edema During 30-d Strict Head-down Tilt Bed Rest and CO2 Exposure (P24-036-19)

ObjectivesSome astronauts returning from missions to the International Space Station (ISS) have developed ophthalmic structural changes, including optic disc edema. Incidence of optic disc edema among astronauts has been linked to one-carbon pathway genetic variants and B-vitamin status. A recent 30-d 6-degree head-down tilt bed rest study in which all subjects were exposed to 0.5% CO2 documented the occurrence of optic disc edema in 5 of 11 subjects. The objective of this study was to determine the effect of one-carbon pathway genetics and B-vitamin status on the incidence of optic disc edema in the bed rest subjects. MethodsThe study was conducted at the: envihab facility at the German Aerospace Center in Cologne, Germany. Subjects (6 M/5F) were healthy volunteers, 33 ± 8 y (mean ± SD), having a mean BMI of 23.4 ± 2.2 kg/m2. After a 14-d ambulatory phase in a standard environment (i.e., not hypercapnic), a blood sample was collected to assess vitamin status and single nucleotide polymorphisms (SNPs) associated with one carbon metabolism. We focused on two SNPs (rs1801394, MTRR 66 and rs1979227, SHMT1 1420) based on our earlier findings in astronauts (Zwart et al., FASEB J, 30:141–8, 2016). The 30-d bed rest began after collection of this sample. Optical coherence tomography images were collected before, during (days 15 and 30), and after (6 and 13 days after reambulation) bed rest, and the change in total retinal thickness (TRT) at various distances from Bruch’s membrane opening (BMO) was evaluated against the number of MTRR A66G G alleles and SHMT1 C1420T C alleles. ResultsThe change in TRT at various distances from the BMO in bed rest subjects exposed to mild hypercapnia and headward fluid shifts was strongly associated with the number of MTRR 66 G and SHMT1 1420 C alleles. ConclusionsThis finding may increase understanding of mechanisms involved in optic disc edema in astronauts and patients on Earth, and hence lead to development of targeted countermeasures. Funding SourcesThis work was funded by the NASA Human Health Countermeasures Element of the NASA Human Research Program.

A Year on the International Space Station: Implementing a Long-Duration Biomedical Research Mission.

INTRODUCTION: The year-long mission of American astronaut Scott Kelly and Russian cosmonaut Mikhail Kornienko included the most complex biomedical experiments ever conducted on the International Space Station-and arguably in human spaceflight-to establish insight into human health risks of interplanetary exploration. Focusing on risk mitigation, NASA conducted investigations that addressed spaceflight health hazards to varying degrees. This pilot mission was initiated to gain further knowledge and monitor the physiological, psychological, and medical effects of long-duration exposure to spaceflight.METHODS: NASA's Human Research Program and the Russian Academy of Sciences' Institute of Biomedical Problems identified more than 20 biomedical risk-reduction research investigations to be conducted on the two crewmembers before, during, and after their yearlong expedition. A database of results, as well as observations on programmatic resources, was collected to understand essential elements for future spaceflight health studies.RESULTS: Statistical rigor requires additional testing at a length of 1 yr to demonstrate the presence or absence of unacceptable deleterious effects, and to permit extrapolation to longer durations in space. Review of experimental procedures from this mission suggests potential efficiencies for future investigations.DISCUSSION: The Kelly-Kornienko 1-yr mission demonstrated the importance of continuing joint investigations with the adoption of standard measures for rigorous comparisons across disparate populations. It identified improvements to collaborative processes across national and international scientific research programs. Additional studies will inform the development of an integrated applied research methodology for the space station and future interplanetary expeditions.Charles JB, Pietrzyk RA. A year on the International Space Station: implementing a long-duration biomedical research mission. Aerosp Med Hum Perform. 2019; 90(1):4-11.

VaPER: The Development of Spaceflight Associated Neuro‐ocular Syndrome (SANS) During Hypercapnic 6° Head‐Down Tilt Bed Rest; sans Sufficient Sleep?

OBJECTIVETo determine whether the combination of a cephalad fluid shift induced by headdown tilt (HDT) bed rest and chronic exposure to mild hypercapnia for 30 days will alter sleep architecture and circadian rhythm, contributing to characteristics of Spaceflight Associated Neuro‐ocular Syndrome (SANS).METHODSAfter 14 days of ambulatory normocapnic familiarization with the facility and baseline data collection (BDC), eleven subjects (5 female) breathed mild, ambient hypercapnia (0.5% CO2) throughout 30 days of 6° HDT at the German Aerospace Center (DLR): envihab facility. Following HDT, subjects were monitored for an additional 14 days of ambulatory, normocapnic recovery (R). Overnight polysomnography (PSG) was measured using a type‐2 sleep monitoring system, and the PSG was scored by a Polysomnographic Technologist to assess sleep duration, staging, latency, and arousals. Circadian rhythm was assessed by monitoring 24‐hour core body temperature with rectal temperature probes. Arterial PCO2 levels were estimated from transcutaneous PCO2 monitoring throughout sleep. Retinal thickness was measured via optical coherence tomography (OCT); those with increased thickness &gt;50μ in the nasal quadrant were classified as RET+, those &lt;50μ were classified as RET‐. After one night of familiarization with the instrumentation, measurements were collected at six different time points (one BDC, three HDT, and two R).RESULTSWhen comparing RET+ to RET‐, subjects had: significantly less total sleep time (TST) in BDC (345 ± 25 min vs 401 ± 23 min, p &lt; 0.05), HDT4 (303 ± 64 min vs 375 ± 20 min, p &lt; 0.05), HDT28 (344 ± 59 min vs 407 ± 32 min, p &lt; 0.05), and R+4 (344 ± 68 min vs 421 ± 21 min, p &lt; 0.05); significantly less stage 2 (N2) sleep in HDT4 (157 ± 43 min vs 220 ± 9 min, p &lt; 0.05), HDT28 (198 ± 32 min vs 256 ± 21 min, p &lt; 0.05), and R+4 (187 ± 74 min vs 271 ± 32, p &lt; 0.05); significantly more wake after sleep onset (WASO) in HDT4 (147 ± 85 min vs 57 ± 27 min, p &lt; 0.05) and R+4 (134 ± 106 min vs 41 ± 12 min, p &lt; 0.05); and a significantly reduced core body temperature amplitude at BDC (0.3 ± 0.1 deg vs 0.5 ± 0.1 deg, p &lt; 0.05), HDT4 (0.2 ± 0.1 deg vs 0.4 ± 0.1 deg, p &lt; 0.05), HDT28 (0.3 ± 0.1 deg vs 0.4 ± 0.1 deg, p &lt; 0.05), and R+10 (0.3 ± 0.0 deg vs 0.4 ± 0.1 deg, p &lt; 0.05).CONCLUSIONSPrior to and throughout the experimental conditions, when compared to RET‐, RET+ subjects were “short” sleepers and in general had less N2 sleep, greater WASO, and had a lower amplitude of core body temperature. We conclude that insufficient sleep may predispose certain individuals to the development of retinal thickening, a finding of SANS. Objective PSG may be a potential variable to consider when determining astronaut spaceflight duration.Support or Funding InformationNASA Human Research Program NNJ14ZSA001NThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Human Performance in Altered-Gravity Environments

Human Performance in Altered-Gravity Environments

Integrating spaceflight human system risk research

NASA is working to increase the likelihood of exploration mission success and to maintain crew health, both during exploration missions and long term after return to Earth. To manage the risks in achieving these goals, a system modelled after a Continuous Risk Management framework is in place. “Human System Risks” (Risks) have been identified, and 32 are currently being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Inter-disciplinary ties between the research efforts supporting each Risk have been identified; however, efforts to identify and benefit from these connections have been mostly ad hoc. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioural, vehicle, and organizational aspects of exploration missions must be integrated across Risks and disciplines. This paper discusses how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information enables identification and visualization of connections between Risks and research efforts in a systematic and standardized manner. This paper also discusses the applications of the visualizations and insights into research planning, solicitation, and decision-making processes.

Carotid Artery Structure during and after Long‐Duration Space Flight

Space flight missions may expose astronauts to increased risk of oxidative stress and inflammatory damage induced by a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Given that evidence exists that these factors can accelerate the development of atherosclerosis, the purpose of this investigation is to determine whether long‐duration space flight (&gt;4 months) on the International Space Station results in structural changes in the carotid artery.METHODSCarotid artery intima‐media thickness (cIMT) and diameter during systole (Ds) and diastole (Dd) were measured using standard ultrasound (VividQ, GE Healthcare) in 10 astronauts (9 M, 1 F) approximately 180 and 60 days before launch, at approximately 15 (FD15) and 60 days of flight (FD60), within two weeks before landing (R‐14), and within one week after landing. Pre‐ and post‐flight measures were obtained after the subjects had been supine for at least 20 min. Inflight measures were acquired by trained astronauts while being guided by an expert sonographer on the ground using telemedicine techniques. Carotid artery distensibility coefficient was calculated (cDC = (Ds2−Dd2)/(PP·Dd2); Gepner et al., Stroke 45: 48–53, 2014). Pre‐flight data were averaged to represent baseline. Results were analyzed using one‐way repeated measures ANOVA.RESULTSCarotid artery diameters during systole (Ds FD15: 7.6 ± 0.4; FD60: 7.6 ± 0.4; R‐14: 7.7 ± 0.4 mm; mean ± SD) and diastole (Dd FD15: 7.2± 0.3; FD60: 7.3 ± 0.4; R‐14: 7.3 ± 0.5 mm) were significantly greater during space flight than pre‐ (Ds: 7.3 ± 0.4; Dd: 6.9 ± 0.4 mm) and post‐flight (Ds: 7.4 ± 0.4; Dd: 7.1 ± 0.5 mm). There was a main effect of time on cIMT, but post‐hoc analyses did not reveal significant difference from pre‐flight (Pre: 0.58 ± 0.09 mm) at any time point (FD15: 0.58 ± 0.14; FD60: 0.54 ± 0.09; R‐14: 0.54 ± 0.09; Post: 0.62 ± 0.10 mm). Although pre‐flight cDC (0.0028 ± 0.0011/mmHg) was not different than in‐flight (FD15: 0.0023 ± 0.0011; FD60: 0.0020 ± 0.0008; R‐14: 0.0023 ± 0.0012/mmHg), post‐flight cDC (0.0019 ± 0.0010/mmHg) was significantly less than pre‐flight.CONCLUSIONSAlthough the carotid artery was distended chronically during space flight and cDC was decreased in the week after landing, in these astronauts pathological remodeling of this vessel was not evident.Support or Funding InformationSupported by the NASA Human Research Program

Translating Basic Research to Astronaut Health in Space: NASA Ames Rodent Specimen Biobanking for the Human Research Program

Abstract As an extension of NASA Ames’ long history and sustaining international collaboration for sharing tissues acquired from one-off spaceflight experiments, we have recently established a new mobile operation for acquiring small animal biospecimens from ongoing ground-based studies supported by the NASA Human Research Program (HRP) organized at Johnson Space Center (JSC). Goals of Ames’ Biospecimen Sharing Programs (BSPs) are to: (1) advance understanding of physiological responses and adaptations to the space environment utilizing animal models in support of fundamental space and gravitational biology research, and to promote human health in space and on Earth, (2) provide a repository of high-quality, well-preserved, and carefully archived and maintained biospecimens by applying modern approaches and established best practices in the biobanking field, and (3) establish a database for gathering broad and comprehensive scientific information corresponding to these samples, including cutting edge techniques for tracking and archiving of structural, descriptive, and administrative metadata. This program, modeled after contemporary human and animal biobanking initiatives, is yielding a rich archive of quality specimens that can be used to address a broad range of current and future scientific questions relevant to NASA Life Sciences, Exploration Medicine, and beyond.

A call for research to assess and promote functional resilience in astronaut crews.

to the editor: NASA plans to send humans to Mars in about 20 years. The NASA Human Research Program supports research to mitigate the major identified risks to human health and performance on such long-duration missions. However, there will undoubtedly be unforeseen events on any mission of this

Vision Issues and Space Flight: Evaluation of One‐Carbon Metabolism Polymorphisms

Intermediates of the one‐carbon metabolic pathway are altered in astronauts who experience vision‐related issues during and after space flight. Serum concentrations of homocysteine, cystathionine, 2‐methylcitric acid, and methylmalonic acid were higher in astronauts with ophthalmic changes than in those without (Zwart et al., J Nutr, 142:427‐31, 2012). These differences existed before, during, and after flight. Potential confounding factors did not explain the differences. Genetic polymorphisms could contribute to these differences, and could help explain why crewmembers on the same mission do not all have ophthalmic issues, despite the same environmental factors (e.g., microgravity, exercise, diet). A follow‐up study was conducted to evaluate 5 polymorphisms of enzymes in the one‐carbon pathway, and to evaluate how these relate to vision and other ophthalmic changes after flight. Preliminary evaluations of the genetic data indicate that all of the crewmembers with the MTRR GG genotype had vision issues to one degree or another. However, not everyone who had vision issues had this genetic polymorphism, so the situation is more complex than the involvement of this single polymorphism. Metabolomic and further data analyses are underway to clarify these findings, but the preliminary assessments are promising. This study was funded by the Human Health Countermeasures Element of the NASA Human Research Program.

Dietary and Urinary Sulfur Can Predict Changes in Bone Metabolism During Space Flight

Mitigating bone loss is critical for space exploration, and diet can play a major role in this effort. Previous studies showed that dietary composition could influence bone resorption during bed rest. In this study we examined the role of dietary intake patterns in bone mineral loss in astronauts during space flight. Crewmembers were asked to consume, for 4 days at a time, prescribed menus with either a low (0.3‐0.6 g/mEq) or high (1.0‐1.3 g/mEq) ratio of animal protein to potassium (APro:K). Menus were developed for each crewmember, and were designed to meet both crew preferences and study constraints. Intakes of energy, total protein, calcium, and sodium were held relatively constant between the 2 diets. The order of the menus was randomized, and crews completed each set (low and high) once before and twice during space flight, for a total of 6 controlled diet sessions. One in‐flight session monitored typical dietary intake. On the last day of each of the 4‐d controlled diet sessions, 24‐h urine samples were collected, along with a fasting blood sample on the morning of the 5th day. As of this writing, data are available from 14 crewmembers. The final 3 subjects' in‐flight samples are awaiting return from the International Space Station via SpaceX Dragon capsule. Preliminary analyses show that urinary excretion of sulfate (normalized to lean body mass) is a significant predictor of urinary bone resorption marker n‐telopeptide (NTX). Dietary sulfate (normalized to lean body mass) is also a significant predictor of urinary NTX. The results from this study will be important to better understand diet and bone interrelationships during space flight as well as on Earth. Funded by the Human Health Countermeasures Element of the NASA Human Research Program.