Molecular and physiological changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match those of long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiological and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

DNA Damage and Radiosensitivity in Blood Cells from Subjects Undergoing 45 Days of Isolation and Confinement: An Explorative Study.

The effect of confined and isolated experience on astronauts' health is an important factor to consider for future space exploration missions. The more confined and isolated humans are, the more likely they are to develop negative behavioral or cognitive conditions such as a mood decline, sleep disorder, depression, fatigue and/or physiological problems associated with chronic stress. Molecular mediators of chronic stress, such as cytokines, stress hormones or reactive oxygen species (ROS) are known to induce cellular damage including damage to the DNA. In view of the growing evidence of chronic stress-induced DNA damage, we conducted an explorative study and measured DNA strand breaks in 20 healthy adults. The participants were grouped into five teams (missions). Each team was composed of four participants, who spent 45 days in isolation and confinement in NASA's Human Exploration Research Analog (HERA). Endogenous DNA integrity, ex-vivo radiation-induced DNA damage and the rates of DNA repair were assessed every week. Our results show a high inter-individual variability as well as differences between the missions, which cannot be explained by inter-individual variability alone. The ages and sex of the participants did not appear to influence the results.

Brains in space: the importance of understanding the impact of long-duration spaceflight on spatial cognition and its neural circuitry.

Fifty years after the first humans stepped on the Moon, space faring nations have entered a new era of space exploration. NASA's reference mission to Mars is expected to comprise 1100 days. Deep space exploratory class missions could even span decades. They will be the most challenging and dangerous expeditions in the history of human spaceflight and will expose crew members to unprecedented health and performance risks. The development of adverse cognitive or behavioral conditions and psychiatric disorders during those missions is considered a critical and unmitigated risk factor. Here, we argue that spatial cognition, i.e., the ability to encode representations about self-to-object relations and integrate this information into a spatial map of the environment, and their neural bases will be highly vulnerable during those expeditions. Empirical evidence from animal studies shows that social isolation, immobilization, and altered gravity can have profound effects on brain plasticity associated with spatial navigation. We provide examples from historic spaceflight missions, spaceflight analogs, and extreme environments suggesting that spatial cognition and its neural circuitry could be impaired during long-duration spaceflight, and identify recommendations and future steps to mitigate these risks.

Exercise-induced changes in brain activity during memory encoding and retrieval after long-term bed rest.

Episodic memory depends decisively on the hippocampus and the parahippocampal gyrus, brain structures that are also prone to exercise-induced neuroplasticity and cognitive improvement. We conducted a randomized controlled trial to investigate the effects of a high-intensity exercise program in twenty-two men resting in bed for 60 days on episodic memory and its neuronal basis. All participants were exposed to 60 days of uninterrupted bed rest. Eleven participants were additionally assigned to a high-intensity interval training that was performed five to six times weekly for 60 days. Episodic memory and its neural basis were determined four days prior to and on the 58th day of bed rest using functional magnetic resonance imaging (fMRI). We found increased BOLD signal in the left hippocampus and parahippocampal gyrus in the non-exercising group compared to the exercising bed rest group whereas the mnemonic performance did not differ significantly. These findings indicate a higher neuronal efficiency in the training group during memory encoding and retrieval and may suggest a dysfunctional mechanism in the non-exercising bed rest group induced by two months of physical inactivity. Our results provide further support for the modulating effects of physical exercise and adverse implications of a sedentary lifestyle and bedridden patients.

Associations of bedroom PM2.5, CO2, temperature, humidity, and noise with sleep: An observational actigraphy study.

OBJECTIVE: Climate change and urbanization increasingly cause extreme conditions hazardous to health. The bedroom environment plays a key role for high-quality sleep. Studies objectively assessing multiple descriptors of the bedroom environment as well as sleep are scarce. METHODS: Particulate matter with a particle size <2.5 µm (PM2.5), temperature, humidity, carbon dioxide (CO2), barometric pressure, and noise levels were continuously measured for 14 consecutive days in the bedroom of 62 participants (62.9% female, mean ± SD age: 47.7 ± 13.2 years) who wore a wrist actigraph and completed daily morning surveys and sleep logs. RESULTS: In a hierarchical mixed effect model that included all environmental variables and adjusted for elapsed sleep time and multiple demographic and behavioral variables, sleep efficiency calculated for consecutive 1-hour periods decreased in a dose-dependent manner with increasing levels of PM2.5, temperature, CO2, and noise. Sleep efficiency in the highest exposure quintiles was 3.2% (PM2.5, p < .05), 3.4% (temperature, p < .05), 4.0% (CO2, p < .01), and 4.7% (noise, p < .0001) lower compared to the lowest exposure quintiles (all p-values adjusted for multiple testing). Barometric pressure and humidity were not associated with sleep efficiency. Bedroom humidity was associated with subjectively assessed sleepiness and poor sleep quality (both p < .05), but otherwise environmental variables were not statistically significantly associated with actigraphically assessed total sleep time and wake after sleep onset or with subjectively assessed sleep onset latency, sleep quality, and sleepiness. Assessments of bedroom comfort suggest subjective habituation irrespective of exposure levels. CONCLUSIONS: These findings add to a growing body of evidence highlighting the importance of the bedroom environment-beyond the mattress-for high-quality sleep.

Extreme environments for understanding brain and cognition.

Can life in extreme environments foster our understanding of the limits and adaptability of cognition and brain plasticity? We review characteristics of spaceflight and spaceflight analogues, such as bed rest, dry immersion, parabolic flights, and isolated and controlled confinement, and discuss the potential of utilizing these research settings to advance cognitive neuroscience.

Future research directions to identify risks and mitigation strategies for neurostructural, ocular, and behavioral changes induced by human spaceflight: A NASA-ESA expert group consensus report.

A team of experts on the effects of the spaceflight environment on the brain and eye (SANS: Spaceflight-Associated Neuro-ocular Syndrome) was convened by NASA and ESA to (1) review spaceflight-associated structural and functional changes of the human brain and eye, and any interactions between the two; and (2) identify critical future research directions in this area to help characterize the risk and identify possible countermeasures and strategies to mitigate the spaceflight-induced brain and eye alterations. The experts identified 14 critical future research directions that would substantially advance our knowledge of the effects of spending prolonged periods of time in the spaceflight environment on SANS, as well as brain structure and function. They used a paired comparison approach to rank the relative importance of these 14 recommendations, which are discussed in detail in the main report and are summarized briefly below.

Dynamic ensemble prediction of cognitive performance in spaceflight.

During spaceflight, astronauts face a unique set of stressors, including microgravity, isolation, and confinement, as well as environmental and operational hazards. These factors can negatively impact sleep, alertness, and neurobehavioral performance, all of which are critical to mission success. In this paper, we predict neurobehavioral performance over the course of a 6-month mission aboard the International Space Station (ISS), using ISS environmental data as well as self-reported and cognitive data collected longitudinally from 24 astronauts. Neurobehavioral performance was repeatedly assessed via a 3-min Psychomotor Vigilance Test (PVT-B) that is highly sensitive to the effects of sleep deprivation. To relate PVT-B performance to time-varying and discordantly-measured environmental, operational, and psychological covariates, we propose an ensemble prediction model comprising of linear mixed effects, random forest, and functional concurrent models. An extensive cross-validation procedure reveals that this ensemble outperforms any one of its components alone. We also identify the most important predictors of PVT-B performance, which include an individual's previous PVT-B performance, reported fatigue and stress, and temperature and radiation dose. This method is broadly applicable to settings where the main goal is accurate, individualized prediction of human behavior involving a mixture of person-level traits and irregularly measured time series.

Effects of two months of bed rest and antioxidant supplementation on attentional processing.

Physical inactivity across the lifespan is a growing public health concern affecting the cardiovascular, musculoskeletal, and central nervous system. Data on the effects of dietary antioxidants as neuroprotective treatments when physical activity levels are impaired are lacking. In this randomized controlled study, twenty young healthy men underwent 60 days of bed rest. Participants were randomly assigned to a treatment group (n = 10) receiving a daily antioxidant supplement comprising polyphenols, omega-3 fatty acids, vitamin E, and selenium or a control group (n = 10). Event-related potentials (ERPs) and behavioral data from a three-stimulus oddball paradigm were collected eight days before bed rest, after 60 days of immobilization, and after eight days of recovery. After two months of bed rest, we found a significant decrease in task efficiency irrespective of the treatment that was corroborated by lower ERPs in fronto-central and parietal brain regions. Neither behavioral nor electrocortical data returned to baseline values after eight days of recovery. Our results provide support for the adverse and persistent neurobehavioral effects of prolonged bed rest, which could not be mitigated by antioxidant supplementation. These findings raise important implications for situations in which physical activity levels become severely restricted such as medical conditions or sedentary lifestyles.

Head-Down Tilt Position, but Not the Duration of Bed Rest Affects Resting State Electrocortical Activity.

Adverse cognitive and behavioral conditions and psychiatric disorders are considered a critical and unmitigated risk during future long-duration space missions (LDSM). Monitoring and mitigating crew health and performance risks during these missions will require tools and technologies that allow to reliably assess cognitive performance and mental well-being. Electroencephalography (EEG) has the potential to meet the technical requirements for the non-invasive and objective monitoring of neurobehavioral conditions during LDSM. Weightlessness is associated with fluid and brain shifts, and these effects could potentially challenge the interpretation of resting state EEG recordings. Head-down tilt bed rest (HDBR) provides a unique spaceflight analog to study these effects on Earth. Here, we present data from two long-duration HDBR experiments, which were used to systematically investigate the time course of resting state electrocortical activity during prolonged HDBR. EEG spectral power significantly reduced within the delta, theta, alpha, and beta frequency bands. Likewise, EEG source localization revealed significantly lower activity in a broad range of centroparietal and occipital areas within the alpha and beta frequency domains. These changes were observed shortly after the onset of HDBR, did not change throughout HDBR, and returned to baseline after the cessation of bed rest. EEG resting state functional connectivity was not affected by HDBR. The results provide evidence for a postural effect on resting state brain activity that persists throughout long-duration HDBR, indicating that immobilization and inactivity per se do not affect resting state electrocortical activity during HDBR. Our findings raise an important issue on the validity of EEG to identify the time course of changes in brain function during prolonged HBDR, and highlight the importance to maintain a consistent body posture during all testing sessions, including data collections at baseline and recovery.

Regular exercise counteracts circadian shifts in core body temperature during long-duration bed rest.

With NASA's plans for the human exploration of Mars, astronauts will be exposed to mission durations much longer than current spaceflight missions on the International Space Station. These mission durations will increase the risk for circadian misalignment. Exercise has gained increasing interest as a non-pharmacological aid to entrain the circadian system. To assess the potential of exercise as a countermeasure to mitigate the risk for circadian disorders during spaceflight, we investigated the effects of long-term head-down tilt bed rest (HDBR) with and without exercise on the circadian rhythm of core body temperature. Core body temperature was recorded for 24 h using a rectal probe in sixteen healthy men (age: 30.5 ± 7.5 years (mean ± SD)) after 7 days and 49 days of HDBR. Five participants underwent HDBR only (CTR), five participants underwent HDBR and performed resistive exercises (RE), and six participants underwent HDBR and performed resistive exercises superimposed with vibrations (RVE). The exercise was scheduled three times per week. CTR showed a phase delay of 0.69 h. In contrast, both exercise groups were characterized by a phase advance (0.45 h for RE and 0.45 h for RVE; p = 0.026 for interaction between time and group). These findings suggest that resistive exercise (with or without vibration) may also serve as a countermeasure during spaceflight to mitigate circadian misalignments. The results could also be important for increasing awareness about the role of circadian disorders in long-term bedridden patients.

Continuous and Intermittent Artificial Gravity as a Countermeasure to the Cognitive Effects of 60 Days of Head-Down Tilt Bed Rest.

Environmental and psychological stressors can adversely affect astronaut cognitive performance in space. This study used a 6° head-down tilt bed rest (HDBR) paradigm to simulate some of the physiologic changes induced by microgravity. Twenty-four participants (mean ± SD age 33.3 ± 9.2 years, N = 16 men) spent 60 consecutive days in strict HDBR. They were studied in three groups of eight subjects each. One group served as Control, whereas the other two groups received either a continuous or intermittent artificial gravity (AG) countermeasure of 30 min centrifugation daily (1 g acceleration at the center of mass and 2 g at the feet). Participants performed all 10 tests of NASA's Cognition battery and a brief alertness and mood survey repeatedly before, during, and after the HDBR period. Test scores were adjusted for practice and stimulus set difficulty effects. A modest but statistically significant slowing across a range of cognitive domains was found in all three groups during HDBR compared to baseline, most consistently for sensorimotor speed, whereas accuracy was unaffected. These changes were observed early during HDBR and did not further worsen or improve with increasing time in HDBR, except for emotion recognition performance. With increasing time spent in HDBR, participants required longer time to decide which facial emotion was expressed. They were also more likely to select categories with negative valence over categories with neutral or positive valence. Except for workload, which was rated lower in the Control group, continuous or intermittent AG did not modify the effect of HDBR on cognitive performance or subjective responses. Participants expressed several negative survey responses during HDBR relative to baseline, and some of the responses further deteriorated during recovery, which highlights the importance of adequate medical and psychological support during extended duration HDBR studies. In conclusion, 60 days of HDBR were associated with moderate cognitive slowing and changes in emotion recognition performance, but these effects were not mitigated by either continuous or intermittent exposure to AG for 30 min daily.

Impaired Attentional Processing During Parabolic Flight.

Previous studies suggest that altered gravity levels during parabolic flight maneuvers affect spatial updating. Little is known about the impact of the experimental setting and psychological stressors associated with parabolic flight experiments on attentional processes. To address this gap, we investigated the level of alertness, selective and sustained attention in 1 and 0 g using a Go/No-Go Continuous Performance Task. We also identified several parameters associated with the experimental set-up of a parabolic flight that could be expected to affect attentional processing. These included the use of scopolamine, sleep quality prior to the flight day, participant's stress level as well as mood and anxiety state before and after the parabolic flight. We observed a deterioration in attentional processing prior to the first parabola that was further aggravated in weightlessness and returned to baseline after the last parabola. Reaction Time, Hit and False Alarm Rate were moderately correlated with self-reported anxiety state, but not cortisol levels or emotional states. The use of scopolamine had minor effects on Reaction Time. Our results confirm previous studies reporting impairments of cognitive performance in 0 g, and highlight important aspects that should be considered for the design of behavioral research experiments in future parabolic flight campaigns.

Long-Term Bed Rest Delays the Circadian Phase of Core Body Temperature.

Spaceflight can be associated with sleep loss and circadian misalignment as a result of non-24 h light-dark cycles, operational shifts in work/rest cycles, high workload under pressure, and psychological factors. Head-down tilt bed rest (HDBR) is an established model to mimic some of the physiological and psychological adaptions observed in spaceflight. Data on the effects of HDBR on circadian rhythms are scarce. To address this gap, we analyzed the change in the circadian rhythm of core body temperature (CBT) in two 60-day HDBR studies sponsored by the European Space Agency [n = 13 men, age: 31.1 ± 8.2 years (M ± SD)]. CBT was recorded for 36 h using a non-invasive and validated dual-sensor heatflux technology during the 3rd and the 8th week of HDBR. Bed rest induced a significant phase delay from the 3rd to the 8th week of HDBR (16.23 vs. 16.68 h, p = 0.005, g = 0.85) irrespective of the study site (p = 0.416, g = -0.46), corresponding to an average phase delay of about 0.9 min per day of HDBR. In conclusion, long-term bed rest weakens the entrainment of the circadian system to the 24-h day. We attribute this effect to the immobilization and reduced physical activity levels associated with HDBR. Given the critical role of diurnal rhythms for various physiological functions and behavior, our findings highlight the importance of monitoring circadian rhythms in circumstances in which gravity or physical activity levels are altered.

Effects of head-down tilt bed rest plus elevated CO2 on cognitive performance.

Microgravity and elevated CO2 levels are two important environmental spaceflight stressors that can adversely affect astronaut cognitive performance and jeopardize mission success. This study investigated the effects of 6° head-down tilt bed rest (HDBR) with (n = 11 participants, 30-day HDBR) and without (n = 8 participants, 60-day HDBR) elevated ambient (3.73 mmHg) CO2 concentrations on cognitive performance. Participants of both groups performed all 10 tests of NASA's Cognition battery and a brief alertness and mood survey repeatedly before, during, and after the HDBR period. Test scores were adjusted for practice and stimulus set effects. Concentrating on the first 30 days of HDBR, a modest but statistically significant slowing across a range of cognitive domains was found in both groups (controls: -0.37 SD; 95% CI -0.48, -0.27; adjusted P < 0.0001; CO2: -0.25 SD; 95% CI -0.34, -0.16; adjusted P < 0.001), most prominently for sensorimotor speed. These changes were observed early during HDBR and did not further deteriorate or improve with increasing time in HDBR. The study found similar cognitive effects of HDBR irrespective of CO2 levels, suggesting that elevated CO2 neither ameliorated nor worsened the HDBR effects. In both groups, cognitive performance after 15 days of recovery was statistically indistinguishable from pre-HDBR performance. However, subjects undergoing 60 days of HDBR rated themselves as feeling more sleepy, tired, physically exhausted, stressed, and unhealthy during recovery compared to their 30-day counterparts.NEW AND NOTEWORTHY This study investigated the effects of prolonged head-down tilt bed rest with and without elevated (3.73 mmHg) levels of ambient CO2 on cognitive performance across a range of cognitive domains and is one of the few studies investigating combined effects of environmental stressors prevalent in spaceflight. The study showed moderate declines in cognitive speed induced by head-down tilt bed rest and suggests that exposure to elevated levels of ambient CO2 did not modify this effect.

COVID-19-The largest isolation study in history: the value of shared learnings from spaceflight analogs.

The world is currently experiencing the largest isolation experiment in history. In an attempt to slow down the spread of the COVID-19 pandemic numerous countries across the world have been shutting down economies, education, and public life. Governments have mandated strict regulations of quarantine and social distancing in an unprecedented manner. The effects of these measures on brain, behavior, neuro-humoral and immunological responses in humans are largely unknown. Life science research for space exploration has a long history in using high-fidelity spaceflight analogs to better understand the effect of prolonged isolation and confinement on genes, molecules, cells, neural circuits, and physiological systems to behavior. We here propose to leverage the extensive experience and data from these studies and build a bridge between spaceflight research and clinical settings to foster transdisciplinary approaches to characterize the neurobehavioral effects on the immune system and vice versa. These approaches are expected to develop innovative and efficient health screening tools, diagnostic systems, and treatments to mitigate health risks associated with isolation and confinement on Earth and during future exploratory spaceflight missions.

Combined protein and calcium ß-hydroxy-ß-methylbutyrate induced gains in leg fat free mass: a double-blinded, placebo-controlled study.

BACKGROUND: The leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) is widely used as an ergogenic supplement to increase resistance-training induced gains in fat free mass (FFM) and strength in healthy adults. Recent studies have questioned the effectiveness of HMB, particularly when a high protein diet is habitually consumed. To investigate the additive resistance-training induced effects of HMB and protein in untrained individuals, we conducted a randomized double-blind, placebo-controlled study that compared the effects of combined protein and HMB supplementation to protein supplementation alone on FFM and muscle strength after 12-week resistance training. METHODS: Sixteen healthy men (22 ± 2 yrs) performed a periodized resistance-training program for twelve weeks (four sessions per week). The program comprised two mesocycles, characterized by a linear periodization and non-linear periodization, respectively, and separated by a 1-week tapering period. All participants received 60 g of whey protein on training days and 30 g of whey protein (WP) on non-training days. Participants were randomly assigned to additionally receive 3 g of calcium HMB (WP + HMB) or a placebo (WP + PLA). Body composition and physical fitness were tested before and after the 12-week training program. Whole-body and arm and leg fat free mass (FFM) were assessed by bioimpedance spectroscopy; upper arm and leg fat free cross sectional areas were also quantified using magnetic resonance imaging (MRI); upper and lower body strength were measured by One-repetition maximum (1-RM) bench press and leg press. RESULTS: Whole-body and segmental FFM increased in both groups (P <  0.001). However, gains in leg FFM were higher in WP + HMB vs. WP + PLA (arm FFM: + 6.1% vs. + 9.2%, P = 0.2; leg FFM: + 14.2% vs. + 7.0%, P <  0.01). No change in fat mass was observed (P = 0.59). 1-RM increased in both groups (P <  0.001). CONCLUSIONS: Combined protein and HMB supplementation resulted in segmental, but not whole-body increases in FFM compared to protein supplementation alone. These findings could explain some of the controversial effects of HMB reported in previous studies and have practical implications for maximizing training-induced gains in FFM and clinical conditions associated with skeletal muscle deconditioning such as aging, sedentary lifestyles, bed rest and spaceflight.

Reduced vagal modulations of heart rate during overwintering in Antarctica.

Long-duration Antarctic expeditions are characterized by isolation, confinement, and extreme environments. Here we describe the time course of cardiac autonomic modulation assessed by heart rate variability (HRV) during 14-month expeditions at the German Neumayer III station in Antarctica. Heart rate recordings were acquired in supine position in the morning at rest once before the expedition (baseline) and monthly during the expedition from February to October. The total set comprised twenty-five healthy crewmembers (n = 15 men, 38 ± 6 yrs, n = 10 women, 32 ± 6 yrs, mean ± SD). High frequency (HF) power and the ratio of low to high frequency power (LF/HF) were used as indices of vagal modulation and sympathovagal balance. HF power adjusted for baseline differences decreased significantly during the expedition, indicating a gradual reduction in vagal tone. LF/HF powers ratio progressively shifted toward a sympathetic predominance reaching statistical significance in the final trimester (August to October) relative to the first trimester (February to April). This effect  was particularly pronounced in women. The depression of cardio-vagal tone and the shift toward a sympathetic predominance observed throughout the overwintering suggest a long-term cardiac autonomic modulation in response to isolation and confinement during Antartic overwintering.

High-Intensity Exercise Mitigates Cardiovascular Deconditioning During Long-Duration Bed Rest.

Head-down-tilt bed rest (HDT) mimics the changes in hemodynamics and autonomic cardiovascular control induced by weightlessness. However, the time course and reciprocal interplay of these adaptations, and the effective exercise protocol as a countermeasure need further clarification. The overarching aim of this work (as part of a European Space Agency sponsored long-term bed rest study) was therefore to evaluate the time course of cardiovascular hemodynamics and autonomic control during prolonged HDT and to assess whether high-intensity, short-duration exercise could mitigate these effects. A total of n = 23 healthy, young, male participants were randomly allocated to two groups: training (TRAIN, n = 12) and non-training (CTRL, n = 11) before undergoing a 60-day HDT. The TRAIN group underwent a resistance training protocol using reactive jumps (5-6 times per week), whereas the CTRL group did not perform countermeasures. Finger blood pressure (BP), heart rate (HR), and stroke volume were collected beat-by-beat for 10 min in both sitting and supine positions 7 days before HDT (BDC-7) and 10 days after HDT (R+10), as well as on the 2nd (HDT2), 28th (HDT28), and 56th (HDT56) day of HDT. We investigated (1) the isolated effects of long-term HDT by comparing all the supine positions (including BDC-7 and R+10 at 0 degrees), and (2) the reactivity of the autonomic response before and after long-term HDT using a specific postural stimulus (i.e., supine vs. sitting). Two-factorial linear mixed models were used to assess the time course of HDT and the effect of the countermeasure. Starting from HDT28 onwards, HR increased (p < 0.02) and parasympathetic tone decreased exclusively in the CTRL group (p < 0.0001). Moreover, after 60-day HDT, CTRL participants showed significant impairments in increasing cardiac sympathovagal balance and controlling BP levels during postural shift (supine to sitting), whereas TRAIN participants did not. Results show that a 10-day recovery did not compensate for the cardiovascular and autonomic deconditioning following 60-day HDT. This has to be considered when designing rehabilitation programs-not only for astronauts but also in general public healthcare. High-intensity, short-duration exercise training effectively minimized these impairments and should therefore deserve consideration as a cardiovascular deconditioning countermeasure for spaceflight.