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NASA NTRSDate not supplied

Validation of Fitness for Duty Standards Using Pre- and Post-Flight Capsule Egress and Suited Functional Performance Tasks in Simulated Reduced Gravity

The transition between gravity environments will involve one of the most complex, high-risk phases of exploration missions. The reduced functional capacity caused by physiological deconditioning adaptations in microgravity coupled with the stressors of re-entry into partial gravity environments will increase risks to crew, even with rigorous adherence to inflight countermeasures. Specifically, two high-risk scenarios may be required to be performed soon after gravity transitions: 1) nominal and/or emergency unassisted capsule egress task after return to Earth, and 2) planetary extravehicular activity (EVA) soon after landing on Mars or the Moon. Quantification of crewmember’s functional performance after long-duration spaceflight is necessary to inform concepts of operations for future exploration missions. The overarching aim of this study is to quantify post-landing functional performance with deconditioning after long-duration ISS missions. This study is broken down into two phases. Phase 1 includes a pilot study to assess the overall feasibility and demonstrate the capability to perform mission-like tasks shortly after landing. Phase 2, the Egress Fitness study, which is part of the Complement of Integrated Protocols for Human Exploration Research (CIPHER), uses a task-based approach to characterize functional performance in long-duration ISS crewmembers before flight and shortly after return to Earth. The pilot and full Egress Fitness study includes pre-flight and post-flight testing of simulated emergency egress out of a functional capsule mockup and a Mars gravity EVA simulation at the Active Response Gravity Offload System (ARGOS) facility. The EVA simulation tasks include suit donning, hatch egress, ladder descent, task board cable operations, baggage transfer over sand/rocky regolith, alignment with a rear entry port, and suit egress. The post-flight simulated capsule egress test occurs 1–4 h after landing and the planetary EVA simulation occurs 18–36 h after landing. The full CIPHER Egress Fitness study has additional pre-flight sessions, longer EVA tasks that include traverse and geology sampling, and post-flight sessions on R+1, 4, and 8 to characterize the timeframe of recovery. The Pilot Egress Fitness study has completed baseline and post-flight testing on four crewmembers. All subjects were able to complete the post-flight simulated planetary EVA; three subjects were able to complete the postflight capsule egress simulation. CIPHER study data collection is ongoing. This study will quantify post-landing functional performance in operationally relevant simulations to help inform future planetary concepts of operations shortly after landing.

egress↗
NASA NTRSDate not supplied

Increased Treadmill Running and Lower-Body Resistance Training Intensity May Attenuate Aerobic Capacity Loss During Spaceflight

BACKGROUND: In-flight exercise training is the primary countermeasure to mitigate spaceflight-induced decrements in strength and aerobic capacity. Despite high-quality exercise capabilities and prescriptions aboard the International Space Station (ISS), most astronauts experience strength and aerobic capacity loss; however, significant individual variability exists. Recent findings suggest that greater in-flight running (i.e., distance per session) and lower-body resistance exercise intensity (i.e., load relative to body weight) help preserve strength. Whether similar variables contribute to the preservation of aerobic capacity during spaceflight is unknown. METHODS: A NASA database of exercise performance metrics was used to identify long-duration (≥ 90 days) ISS crew who completed pre- and post-flight aerobic capacity testing (VO2peak, cycle ergometry, n = 44). “Responders” (R) were classified as those that maintained or improved VO2peak (n = 13; 1.4 ± 3.3%), and “non-responders” (NR) were those with the most severe decrements (n = 13; -20.0 ± 3.4%) from pre- to post-flight. In-flight exercise records (cycling, treadmill, resistance exercise) were aggregated across flight weeks. Independent t-tests or Mann-Whitney U tests were used to compare training variables (i.e., frequency, time, intensity, volume) between R and NR. RESULTS: Consistent with the variables contributing to strength protection, in-flight running distance (R: 5.0 ± 0.7; NR: 4.2 ± 1.0 km/session, p = 0.020) and lower-body resistance exercise intensity (R: 110.9 ± 27.3; NR: 91.7 ± 16.5% body weight, p = 0.040) were greater in R than NR. Active running time was also greater in R than NR (R: 101.1 ± 20.4; NR: 82.3 ± 23.5 min/wk; p = 0.039). However, no group differences in cycling frequency, intensity, or time, as well as upper body or core resistance exercise intensity, volume, or frequency were observed. CONCLUSIONS: Although physiologically distinct stimuli, the exercise training variables contributing to the preservation of both strength and aerobic capacity during microgravity exposure appear to be consistent. Increased running time and distance, but not cycling, combined with higher-intensity lower-body resistance exercise, may help mitigate losses in both aerobic capacity and strength during long-duration spaceflight.

Alyssa N Varanoske↗
NASA NTRS2015

Optic Nerve Sheath Diameter: Translating a Terrestrial Focused Technique into a Clinical Monitoring Tool for Spaceflight

Ultrasonography is increasingly used to quickly measure optic nerve sheath diameter (ONSD) when increased intracranial pressure (ICP) is suspected. NASA Space and Clinical Operations Division has been using ground and on‐orbit ultrasound since 2009 as a proxy for ICP in non‐acute monitoring for space medicine purposes. In the terrestrial emergency room population, an ONSD greater than 0.59 cm is considered highly predictive of elevated intracranial pressure. However, this cut‐off limit is not applicable to the spaceflight setting since over 50% of US Operating Segment (USOS) astronauts have an ONSD greater than 0.60 cm even before launch. Crew Surgeon clinical decision‐making is complicated by the fact that many astronauts have history of previous spaceflights. Our data characterize the distribution of baseline ONSD in the astronaut corps, its longitudinal trends in long‐duration spaceflight, and the predictive power of this measure related to increased ICP outcomes.

Mason, Sara↗
NASA NTRS2018

Preparation for Pick-and-Eat Food Production on the International Space Station: Flight Definition for the VEG-04 and VEG-05 Missions

Growth of fresh, nutritious, palatable produce for crew consumption during spaceflight may provide health-promoting, bioavailable nutrients and enhance the dietary experience as we move toward longer-duration missions. Tending plants also may serve as a countermeasure for crew psychological stresses associated with long duration spaceflight. However, requirements to support consistent growth of a variety of high quality, nutritious crops under spaceflight environmental conditions is unknown. This study is exploring the potential to grow plants for food production on the International Space Station (ISS) using the Veggie vegetable production system. Ground testing is underway to compare the impacts of several fertilizer and lighting treatments on growth, quality, and nutritional composition of the leafy green crop mizuna, and the dwarf tomato crop Red Robin when subjected to Veggie ISS environmental conditions. Early testing focused on the leafy crop Tokyo Bekana Chinese cabbage, but ground tests indicated that this plant suffered from stress responses when grown under LEDs and the chronically elevated CO2 levels found on the ISS. Mizuna, a related leafy variety that grows well in the presence of high CO2, and has excellent organoleptic characteristics, was selected as an alternate crop. Tomato crops have been grown using two fertilizer formulations and two pollination techniques, and growth tests using different red:blue lighting environments are underway. Chemical analysis is also being conducted and these data, when coupled with the growth results, will be used to down-select to the two best lighting treatments and best fertilizer treatment for future testing of each crop on the ISS. Additionally, seed-source testing has become important, with mizuna seeds from two different vendors growing very differently. A seed source has been selected, and seed-surface-sanitizing methods have been confirmed for mizuna, but these remain under development for tomato. A crop-handling protocol is also being evaluated to support food safety. All harvests reserve a subset of samples for microbial analysis to determine baseline microbial levels and help establish critical control points for food safety. Testing was initially conducted in hardware analogs of the standard Veggie plant pillows. However, a new Veggie watering system, the Passive Orbital Nutrient Delivery System or PONDS, has been designed and is being prepared for future flight experiments. With the selection of this growth system, ground tests have shifted to analog PONDS systems. Crop tests on ISS, designated VEG-04 for mizuna and VEG-05 for tomato, are planned in 2018 to evaluate any additional impacts of spaceflight on the light and fertilizer conditions down-selected from ground tests. A set of Veggie-specific questions has been developed to characterize the psychological impacts of plant growth and plant-care activities during spaceflight. Organoleptic questionnaires have been developed to assess produce attributes in microgravity taste sessions. These tests for plants growing in the Veggie hardware on ISS will help to mitigate the risk of an inadequate food supply for long duration missions by developing methods and determining hardware requirements to integrate fresh vegetables as a dietary supplement. This research was co-funded by the Human Research Program and Space Biology (MTL1075) in the ILSRA 2015 NRA call.

Veggie↗
NASA NTRS2018

Preparation for Pick-and-Eat Food Production on the International Space Station: Flight Definition for the VEG-04 and VEG-05 Missions

Growth of fresh, nutritious, palatable produce for crew consumption during spaceflight may provide health-promoting, bioavailable nutrients and enhance the dietary experience as we move toward longer-duration missions. Tending plants also may serve as a countermeasure for crew psychological stresses associated with long duration spaceflight. However, requirements to support consistent growth of a variety of high quality, nutritious crops under spaceflight environmental conditions is unknown. This study is exploring the potential to grow plants for food production on the International Space Station (ISS) using the Veggie vegetable production system. Ground testing is underway to compare the impacts of several fertilizer and lighting treatments on growth, quality, and nutritional composition of the leafy green crop mizuna, and the dwarf tomato crop "Red Robin" when subjected to Veggie ISS environmental conditions. Early testing focused on the leafy crop "Tokyo Bekana" Chinese cabbage, but ground tests indicated that this plant suffered from stress responses when grown under LEDs and the chronically elevated CO2 levels found on the ISS. Mizuna, a related leafy variety that grows well in the presence of high CO2, and has excellent organoleptic characteristics, was selected as an alternate crop. Tomato crops have been grown using two fertilizer formulations and two pollination techniques, and growth tests using different red:blue lighting environments are underway. Chemical analysis is also being conducted and these data, when coupled with the growth results, will be used to down-select to the two best lighting treatments and best fertilizer treatment for future testing of each crop on the ISS. Additionally, seed-source testing has become important, with mizuna seeds from two different vendors growing very differently. A seed source has been selected, and seed-surface-sanitizing methods have been confirmed for mizuna, but these remain under development for tomato. A crop-handling protocol is also being evaluated to support food safety. All harvests reserve a subset of samples for microbial analysis to determine baseline microbial levels and help establish critical control points for food safety. Testing was initially conducted in hardware analogs of the standard Veggie plant pillows. However, a new Veggie watering system, the Passive Orbital Nutrient Delivery System or PONDS, has been designed and is being prepared for future flight experiments. With the selection of this growth system, ground tests have shifted to analog PONDS systems. Crop tests on ISS, designated VEG-04 for mizuna and VEG-05 for tomato, are planned in 2018 to evaluate any additional impacts of spaceflight on the light and fertilizer conditions down-selected from ground tests. A set of Veggie-specific questions has been developed to characterize the psychological impacts of plant growth and plant-care activities during spaceflight. Organoleptic questionnaires have been developed to assess produce attributes in microgravity taste sessions. These tests for plants growing in the Veggie hardware on ISS will help to mitigate the risk of an inadequate food supply for long duration missions by developing methods and determining hardware requirements to integrate fresh vegetables as a dietary supplement. This research was co-funded by the Human Research Program and Space Biology (MTL#1075) in the ILSRA 2015 NRA call.

LED light↗
NASA NTRS2005

Human behavioral research in space: quandaries for research subjects and researchers

With the advent of long-duration spaceflight on board the International Space Station (ISS) and possible future missions beyond low Earth orbit (LEO) such as Mars, it is critical that those at NASA have a realistic assessment of the challenges that will face individuals on long-duration missions so that they can develop preventive and real-time countermeasures to behavioral health issues. While space travellers are very interested in having countermeasures to the deleterious effects of space missions, they have a powerful disincentive to participate in this research if they feel it could in any way negatively affect their flight status. The behavioral issues of isolation and confinement for extended-duration space missions are reviewed. Areas of basic and clinical behavioral research are listed. And the classical clinical model for research is not considered appropriate for the current configuration of the space program. The use of analogue environments and advanced statistical analysis are suggested as ways to address the limited spaceflight research opportunities. The challenge of research subject or patient confidentiality vs. mission safety and issues of personal flight status are addressed.

Review, Tutorial↗
NASA NTRS2025

Innovative Drug Selection, Storage, and Shelf-Life Strategies for Exploration Spaceflight

Medications have been a part of space travel dating back to the Apollo missions. A safe and effective medication formulary is essential to maintaining crew health and performance during long-duration spaceflight outside of low Earth orbit (LEO). Distance from Earth creates four key operational changes that increase medical risks, including communication, resupply, crewmember health, and evacuation. The current spaceflight pharmaceutical formulary consists of medications indicated to treat a variety of anticipated medical events and healthcare needs during spaceflight, but depends on a robust consumables resupply chain, which may be strained for a Lunar, and possibly non-existent for a Mars mission. The specific medications selections for the formulary may change to optimally align with the mission, crew compliment, and spacecraft design. Medical support at long-duration exploration missions will differ from LEO missions due to mission duration, lack of consumables resupply, prolonged exposure to space radiation, and the absence of emergency medical return capability. Loss of medication resupply limits or removes the ability to replace medications that have been exhausted or degraded, potentially exacerbating the medical risk posture. To address these anticipated risks, long-duration missions must consider use of novel medical technologies, treatment modalities, and smart medical systems that offer greater crew autonomy, such as physiologically based pharmacokinetic modeling, drug repurposing, on demand drug synthesis, or wearable drug delivery / monitoring devices. Once an ideal formulary for exploration space is determined, it is essential to establish the chemical and physical stability of each medication compound, as well as its safety by identifying its degradation profiles and products. Although few studies have been conducted to provide evidence on the physicochemical stability of pharmaceuticals during space missions, the data suggests that the spaceflight environment may promote degradation in some pharmaceuticals. Formulary drug purity and efficacy should be verified by pharmaceutical stability assessments, and can be realized non-destructively, and accessed in remote environments. Non-destructive pharmaceutical analysis and statistical modelling techniques could optimize exploration spaceflight medical care by enabling early detection of suboptimal therapeutics. Likewise, novel packaging, storage strategies, and dosage form innovations are promising countermeasures to optimize pharmaceutical shelf life, purity, and quality of exploration spaceflight medications. As we prepare for more distant exploration missions, risk management planning for astronaut healthcare should include the assembly of a medication formulary that is comprehensive enough to prevent or treat anticipated medical events, remains safe and chemically stable, and retains sufficient potency to last for the duration of the mission. Following extensive review of the literature, we will present innovative formulary optimization strategies, pharmaceutical stability assessment techniques, and storage and packaging solutions that could enhance drug safety and efficacy for future exploration spaceflight missions.

Vernie R Daniels↗
NASA NTRS2023

Automated Fluidics Device for Extraction and Quantification of miRNA Biomarkers From Blood

Radiation Assessment DuRing Exposure And long-Duration Spaceflight (RADREADS) demonstrates space-compatible point-of-care technology for quantitative biological monitoring of blood miRNA biomarkers in response to long-term low dose radiation exposure. This individualized monitoring approach will inform targeted treatment strategies to maximize medical resource utilization by accounting for individual susceptibility to radiation-related illnesses. As human spaceflight progresses beyond Earth’s magnetic shielding, radiation exposure poses a significant risk to astronaut health and safety. Extended operation in this environment comes with an increased risk of radiation exposure, leading to higher risks of radiation sickness, cancer, central nervous system effects, and degenerative diseases. While conventional physical dosimetry techniques capture radiation dose, individualistic susceptibility to radiation damage is varied. Multiple characteristics, including age, body weight, sex, genetics, and immune status, have been found to influence radiosensitivity (Liu et al. 2011, and Bouffler 2016). This differential response necessitates individualized monitoring and targeted treatment strategies to maximize medical resource utilization; however, a practical diagnostic platform for quantifying long-term, low dose radiation-induced tissue damage does not currently exist. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression by mediating the degradation of messenger RNA. The levels of particular miRNAs are influenced by biological processes such as inflammation and serve as biomarkers for a variety of conditions including cancer (Singh et al. 2017). MicroRNAs are found in various bodily fluids and are amenable to collection via liquid biopsies, providing a minimally invasive and easily quantifiable readout for a variety of radiosensitive reporters. A preliminary signature of 15 spaceflight sensitive miRNA has been identified in rodent and human studies, including miR-21-5p, miR-24-3p, miR-92a-3p, miR-17-5p, miR-16a-3p, miR-34a-3p, and miR-223-3p. These targets generally increased expression with radiation dose and linear energy transfer, though variation between individuals is not yet described. Current gaps in the field include a lack of understanding of longitudinal biological responses to long-term, low dose radiation exposure and the absence of space-compatible point-of-care technology for quantitative biological monitoring. In this body of work, we aim to develop an automated bleed-to-read system to process whole blood for the detection of miRNA biomarkers in order to monitor individualistic responses to radiation exposure. This will be achieved via separating serum (or plasma) from whole blood, followed by extraction, amplification, and quantification of the miRNA using a RT-qPCR reaction. Previously, the WetLab-2 hardware enabled execution of a RT-qPCR reaction aboard ISS; however, it is a manual system that requires crew manipulation and bulky components (Parra et al. 2017). To address these issues, automated fluid handling hardware was developed for each stage of sample preparation. Extraction of total RNA is achieved by sequentially pumping reagents through an off-the-shelf nucleic acid binding column (miRNeasy Serum/Plasma Advanced Kit, Qiagen). This approach eliminates several manual pipetting and centrifuging steps and limits the use of toxic chemicals commonly found in other sample processing techniques. The resulting elution will then be automatically dispensed for RT-qPCR analysis using a compact rotary qPCR (Mic qPCR Cycler, Bio Molecular Systems) that will improve spaceflight compatibility by removing bubbles from the detection region, another challenge highlighted by WetLab-2 (Parra et al. 2017). Efforts are also being made to simplify the RT-qPCR reaction to a 1-step air-dryable mix to improve long-term reagent stability at room temperature and reduce system complexity. By automating the RT-qPCR processes via microfluidic manipulation, RADREADS will reduce crewmember hands-on time and enable the personalized detection of radiation-induced tissue damage during long duration missions. Minimally invasive, longitudinal monitoring of individual’s response to radiation exposure will inform how the physiological system responds to long-term low dose space radiation and enables development of targeted countermeasures by the medical team. Ultimately, this portable technology will require minimal technical expertise and can also be used to monitor miRNA biomarkers associated with other diseases.

Tristen Head↗
NASA NTRS1986

NASA's life sciences program

NASA space missions from the Mercury through the Shuttle program have provided successively more data on the ability of humans to function in space for progressively longer periods of time. The Skylab program encouraged cooperation between medical and engineering personnel in the design of space suits, diet, food preparation, and cleanliness procedures and equipment, and the man-machine interface. Research is now concentrated on supporting man in space, evaluating the effects of the microgravity environment on humans, and modeling encounters with extraterrestrial life and the effects of human activities on terrestrial biota. Current levels of understanding of the physiological causes of human health problems produced by long-duration spaceflight are summarized. Experiments planned for the Shuttle, Spacelab, and the Space Station are outlined, noting the long-term goal of configuring the Space Station so that only food and hydrazine are needed to complete the life support system cycle.

Soffen, Gerald A.↗
NASA NTRS2017

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

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

Lee, S. M. C.↗
NASA NTRS2017

Integrating Bioregenerative Foods into the Exploration Spaceflight Food System

Food, the nutrition it provides, and the eating experiences surrounding it, are central to performance, health, and psychosocial wellbeing on long duration spaceflight missions. Exploration missions will require a spaceflight food system that is safe, nutritious, and acceptable for up to five years, possibly without cold storage. Many of the processed and packaged spaceflight foods currently used on the International Space Station will not retain acceptable quality or required levels of key nutrients under these conditions. The addition of bioregenerative produce to exploration missions may become an important countermeasure to the nutritional gaps and a resource to support psychosocial health. Bioregenerative produce will be central to establishment of Earth-independence as exploration extends deeper into space. However, bioregenerative foods introduce food safety and scarcity risks that must be eliminated prior to crew reliance on these systems. The pathway to Earth independence will require small-scale integration and validation prior to large scale bioregenerative dependence. Near term exploration missions offer the opportunity to establish small scale supplemental salad crop and fruit systems and validate infrastructure reliability, nutritional potential, and the psychosocial benefits necessary to promote further bioregenerative integration.

Douglas, Grace L.↗
NASA NTRSDate not supplied

A Simulated High CO 2 Spaceflight Environment Increases Plant Preference for Ammonium as a Nitrogen Source.

The growth of crops to sustain astronauts will be critical to long-duration spaceflight missions. Carbon dioxide (CO 2 ) concentrations are very high in spaceflight cabin environments, often 5-10X the CO 2 concentration on Earth 1 . It is therefore crucial to understand how plants respond to elevated CO 2 (eCO 2 ). Nitrogen (N) is important for plant survival, though the effects of eCO 2 on plant uptake of different N forms remain poorly understood. Shoot nitrate assimilation may be reduced at eCO 2 due to a decrease in available reducing power through increased carbon fixation and inhibition of photorespiration 2 , suggesting that eCO 2 may increase plant ammonium preference (Figure 1). A deeper understanding of changes in plant nitrogen form preference in response to eCO 2 will inform nutrient optimization for future space crop production and wastewater processing system design requirements 3 in addition to developing future eCO 2 climate-ready crops.

nitrogen↗
NASA NTRSDate not supplied

Neuro-Vestibular Examination During and Following Spaceflight (Vestibular Health)

BACKGROUND Adaptation to microgravity during spaceflight causes neurological disturbances that are either directly or indirectly mediated by the vestibular system. These disturbances can include space motion sickness, spatial disorientation, and cognitive impairment, as well as changes in head-eye coordination, vestibulo-ocular reflexes, and control of posture and locomotion. Otolith-mediated reflex gains appear to adapt rapidly during spaceflight and after landing. However, animal studies have shown that structural modifications of the vestibular sensory apparatus develop during long-duration spaceflight. To date, no studies have characterized the severity of vestibular syndromes experienced by astronauts as a function of the duration of spaceflight or whether the effects are caused by changes at the peripheral end organs, midbrain, cerebellum, or vestibular cortex. OBJECTIVES We are investigating temporal vestibular changes in crewmembers of short, 6-month, and one-year missions to identify trends in adaptation of vestibular health and performance in orbit and after landing. We are also differentiating between peripheral and central vestibular forms of vertigo and oculomotor disorders. METHODS Recordings of eye, head, and body movements, as well as subjective reports of perception of motion, are being used to determine the presence of abnormal eye movements, dysmetria, motion sickness symptoms, and illusions of motion during head or body movements. This includes characterization of temporal trends in central compensation for vestibular (otolith) asymmetry. In-flight examinations are being performed early in the mission (Flight Days 1 and 30) and once every 2-3 months thereafter. Postflight examinations are performed after return (R) from the mission on R+0, R+4, R+9, and R+30. The inflight and postflight motion sickness questionnaires are customized to support data sharing across related studies. Ground-based control testing has been performed on healthy volunteers(18 females, 14 males;38.6 ± 9.2 years) in the laboratory to estimate mean normative responses, and on patients with bilateral vestibulopathy (BVP) (17 females, 13 males; 60.6 ± 13.0 years) at the University of Caen. RESULTS As of September 2024, two crewmembers have completed all preflight, inflight, and postflight testing. Additional crewmembers are currently enrolled and data collection is currently ongoing. For ground testing, BVP patients performed similarly to previous postflight astronauts on R+0 in various walking performance tasks. Three additional body movement perception tasks have been tested. For the Triangle Completion Task, BVP patients had a larger mean angle of deviation and longer mean distance than healthy controls. For the Self-Rotation Task and Distance Perception Task, BVP patients had larger errors than healthy controls. These data suggest that vestibular deficiencies impact all aspects of body movement perception tested; whereas previous studies suggest that vestibular deficiencies are only associated with directional errors, not with overall trajectories/path lengths. These data will be compared to those of crewmembers during early postflight readaptation. RELEVANCE If the observed symptoms in crewmembers are more deleterious after the year-long missions than those documented after 6-month missions, then relevant countermeasures will be required to maintain the health and operational performance of astronauts during longer missions. Depending on the etiology of the vestibular syndrome revealed by these tests, countermeasures will be proposed based on vestibular rehabilitation therapies currently used in patients with vestibular disorders, such as habituation, gaze stabilization, and/or balance training exercises. ACKNOWLEDGEMENT This work is supported by NASA’s Human Research Program Human Health Countermeasures Element.

T R Macaulay↗
NASA NTRS2013

FRET-Aptamer Assays for Bone Marker Assessment, C-Telopeptide, Creatinine, and Vitamin D

Astronauts lose 1.0 to 1.5% of their bone mass per month on long-duration spaceflights. NASA wishes to monitor the bone loss onboard spacecraft to develop nutritional and exercise countermeasures, and make adjustments during long space missions. On Earth, the same technology could be used to monitor osteoporosis and its therapy. Aptamers bind to targets against which they are developed, much like antibodies. However, aptamers do not require animal hosts or cell culture and are therefore easier, faster, and less expensive to produce. In addition, aptamers sometimes exhibit greater affinity and specificity vs. comparable antibodies. In this work, fluorescent dyes and quenchers were added to the aptamers to enable pushbutton, one-step, bind-and-detect fluorescence resonance energy transfer (FRET) assays or tests that can be freeze-dried, rehydrated with body fluids, and used to quantitate bone loss of vitamin D levels with a handheld fluorometer in the spacecraft environment. This work generated specific, rapid, one-step FRET assays for the bone loss marker C-telopeptide (CTx) when extracted from urine, creatinine from urine, and vitamin D congeners in diluted serum. The assays were quantified in nanograms/mL using a handheld fluorometer connected to a laptop computer to convert the raw fluorescence values into concentrations of each analyte according to linear standard curves. DNA aptamers were selected and amplified for several rounds against a 26- amino acid form of CTx, creatinine, and vitamin D. The commonalities between loop structures were studied, and several common loop structures were converted into aptamer beacons with a fluorophore and quencher on each end. In theory, when the aptamer beacon binds its cognate target (CTx bone peptide, creatinine, or vitamin D), it is forced open and no longer quenched, so it gives off fluorescent light (when excited) in proportion to the amount of target present in a sample. This proportional increase in fluorescence is called a "lights on" FRET response. The vitamin D aptamer beacon gives a "lights off" or inversely proportional fluorescence response to the amount of vitamin D present in diluted serum. These FRET-aptamer assays are rapid (<30 minutes), sensitive (low ng/mL detection limits), and quite easy to carry out (add sample, mix, and detect in the handheld reader). Benefits include the speed of the assays as well as the small amount of space taken up by the handheld reader and cuvette assays. The aptamer DNA sequences represent novel additional features of the existing (patent-pending) FRET-aptamer assay platform.

Bruno, John G.↗
NASA NTRS2016

Sleep Environment Recommendations for Future Spaceflight Vehicles

We conducted a comprehensive literature review summarizing optimal sleep hygiene parameters for lighting, temperature, airflow, humidity, comfort, intermittent and erratic sounds, and privacy and security in the sleep environment. We reviewed the design and use of sleep environments in a wide range of cohorts including among aquanauts, expeditioners, pilots, military personnel and ship operators. We also reviewed the specifications and sleep quality data arising from every NASA spaceflight mission, beginning with Gemini. Finally, we conducted structured interviews with individuals experienced in sleeping in non-traditional spaces including oilrig workers, Navy personnel, astronauts, and expeditioners. We also interviewed the engineers responsible for the design of the sleeping quarters presently deployed on the International Space Station. We found that the optimal sleep environment is cool, dark, quiet, and is perceived as safe and private. There are wide individual differences in the preferred sleep environment; therefore modifiable sleeping compartments are necessary to ensure all crewmembers are able to select personalized configurations for optimal sleep. It is possible to utilize lessons learned from prior spaceflight missions and from other industries in order to guide the design of an optimal sleep space suitable for long-duration spaceflight.

spaceflight↗
NASA NTRS2020

Neuro-vestibular Examination During and Following Spaceflight

Adaptation to microgravity during spaceflight causes neurological disturbances that are either directly or indirectly mediated by the vestibular system. These disturbances could include space motion sickness, spatial disorientation, cognitive impairment, as well as changes in head-eye coordination, vestibulo-ocular reflex, and strategies for controlling posture and locomotion. It seems that otolith-mediated reflex gain adapts rapidly over time during spaceflight and after landing. However, animal studies have shown that structural modifications of the vestibular sensory apparatus develop during long-duration spaceflight. To date, no studies have characterized the severity of vestibular syndromes experienced by astronauts as a function of the duration of spaceflight, or whether the effects are caused by changes at the peripheral end organs, midbrain, cerebellum, or vestibular cortex.

Clément, G.↗
NASA NTRS2020

Circulating Mirna Spaceflight Signature Reveals Targets to Mitigate Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration, and long-duration spaceflight and regulates vascular damage caused by simulated deep space radiation. In previous studies, we had identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have confirmed the expression of these proposed spaceflight associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twins Study via direct quantification of miRNAs, miRNA sequencing, and inferring miRNA target levels based on single-cell RNA (scRNA-seq) and single-cell chromatin (scATAC-seq) sequencing data. To demonstrate the physiological relevance of key spaceflight associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs.

Sherina Malkani↗
NASA NTRS2014

Exercise Effects on the Course of Gray Matter Changes Over 70 Days of Bed Rest

Long duration spaceflight affects posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes through direct effects on peripheral changes that result from reduced vestibular stimulation and body unloading. Effects of microgravity on sensorimotor function have been investigated on earth using bed rest studies. Long duration bed rest serves as a space-flight analogue because it mimics microgravity in body unloading and bodily fluid shifts. It has been hypothesized that the cephalad fluid shift that has been observed in microgravity could potentially affect central nervous system function and structure, and thereby indirectly affect sensorimotor or cognitive functioning. Preliminary results of one of our ongoing studies indeed showed that 70 days of long duration head down-tilt bed rest results in focal changes in gray matter volume from pre-bed rest to various time points during bed rest. These gray matter changes that could reflect fluid shifts as well as neuroplasticity were related to decrements in motor skills such as maintenance of equilibrium. In consideration of the health and performance of crewmembers both inand post-flight we are currently conducting a study that investigates the potential preventive effects of exercise on gray matter and motor performance changes that we observed over the course of bed rest. Numerous studies have shown beneficial effects of aerobic exercise on brain structure and cognitive performance in healthy and demented subjects over a large age range. We therefore hypothesized that an exercise intervention in bed rest could potentially mitigate or prevent the effects of bed rest on the central nervous system. Here we present preliminary outcomes of our study.

Koppelmans, V.↗