Impedance threshold device as a countermeasure for spaceflight associated neuro-ocular syndrome (SANS): Mitigating mechanisms in proposed pathophysiology.

Long-duration spaceflight (LDSF) is associated with unique hazards and linked with numerous human health risks including Spaceflight Associated Neuro-ocular Syndrome (SANS). The proposed mechanisms for SANS include microgravity induced cephalad fluid shift and increased Intracranial Pressure (ICP). SANS is a disorder seen only after LDSF and has no direct terrestrial pathologic counterpart as the zero G environment cannot be completely replicated on Earth. Head-down tilt, bed rest studies however have been used as a terrestrial analog and produce the cephalad fluid shift. Some proposed countermeasures for SANS include vasoconstrictive thigh cuffs and lower body negative pressure. Another potential researched countermeasure is the impedance threshold device (ITD) which can reduce ICP. We review the mechanisms of the ITD and its potential use as a countermeasure for SANS.

The Detrimental Effects of Bedrest: Premature Cardiovascular Aging and Dysfunction.

Bedrest as an experimental paradigm or as an in-patient stay for medical reasons has negative consequences for cardiovascular health. The effects of severe inactivity parallel many of the changes experienced with natural aging but over a much shorter duration. Cardiac function is reduced, arteries stiffen, neural reflex responses are impaired, and metabolic and oxidative stress responses impose burden on the heart and vascular systems. The effect of these changes is revealed in studies of integrative function. Aerobic fitness progressively deteriorates with bedrest and tolerance of upright posture is rapidly impaired. In this review we consider the similarities of aging and bedrest-induced cardiovascular deconditioning. We concur with many recent clinical recommendations that early and regular mobility with upright posture will reduce likelihood of hospital-associated disability related to bedrest.

Cardiopulmonary deconditioning and plasma volume loss are not sufficient to provoke orthostatic hypertension.

Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.

The effect of protein or amino acid provision on immobilization-induced muscle atrophy in healthy adults: A systematic review and meta-analysis.

Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta-analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: -0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse-induced muscle atrophy. Although the meta-analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse-induced decline in either outcome measurement. Additional high-quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.

NASA SPRINT exercise program efficacy for vastus lateralis and soleus skeletal muscle health during 70 days of simulated microgravity.

The efficacy of the NASA SPRINT exercise countermeasures program for quadriceps (vastus lateralis) and triceps surae (soleus) skeletal muscle health was investigated during 70 days of simulated microgravity. Individuals completed 6° head-down-tilt bedrest (BR, n = 9), bedrest with resistance and aerobic exercise (BRE, n = 9), or bedrest with resistance and aerobic exercise and low-dose testosterone (BRE + T, n = 8). All groups were periodically tested for muscle (n = 9 times) and aerobic (n = 4 times) power during bedrest. In BR, surprisingly, the typical bedrest-induced decrements in vastus lateralis myofiber size and power were either blunted (myosin heavy chain, MHC I) or eliminated (MHC IIa), along with no change (P > 0.05) in %MHC distribution and blunted quadriceps atrophy. In BRE, MHC I (vastus lateralis and soleus) and IIa (vastus lateralis) contractile performance was maintained (P > 0.05) or increased (P < 0.05). Vastus lateralis hybrid fiber percentage was reduced (P < 0.05) and energy metabolism enzymes and capillarization were generally maintained (P > 0.05), while not all of these positive responses were observed in the soleus. Exercise offsets 100% of quadriceps and approximately two-thirds of soleus whole muscle mass loss. Testosterone (BRE + T) did not provide any benefit over exercise alone for either muscle and for some myocellular parameters appeared detrimental. In summary, the periodic testing likely provided a partial exercise countermeasure for the quadriceps in the bedrest group, which is a novel finding given the extremely low exercise dose. The SPRINT exercise program appears to be viable for the quadriceps; however, refinement is needed to completely protect triceps surae myocellular and whole muscle health for astronauts on long-duration spaceflights.NEW & NOTEWORTHY This study provides unique exercise countermeasures development information for astronauts on long-duration spaceflights. The NASA SPRINT program was protective for quadriceps myocellular and whole muscle health, whereas the triceps surae (soleus) was only partially protected as has been shown with other programs. The bedrest control group data may provide beneficial information for overall exercise dose and targeting fast-twitch muscle fibers. Other unique approaches for the triceps surae are needed to supplement existing exercise programs.

The impact of bed rest on human skeletal muscle metabolism.

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

Retinal venular vessel diameters are smaller during ten days of bed rest.

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m-2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.

Early ambulation versus prolonged bed rest for incidental durotomies in spine procedures: a systematic review and meta-analysis.

Incidental durotomies are frequent complications of spine surgery associated with cerebrospinal fluid (CSF) leak-related symptoms. Management typically involves prolonged bed rest to reduce CSF pressure at the durotomy site. However, early ambulation may be a safer, effective alternative. PubMed, Web of Science, Embase, Cochrane, and Scopus were systematically searched for studies comparing early ambulation (bed rest ≤ 24 h) with prolonged bed rest (> 24 h) for patients with incidental durotomies in spine surgeries. The outcomes of interest were CSF leak, hypotensive headache, additional surgical repair, pseudomeningocele, and pulmonary complications. Systematic reviews and meta-analysis were performed following the Cochrane Handbook for Systematic Reviews of Interventions. We included a total of 704 patients from 6 studies. There was a significant reduction in the incidence of pulmonary complications (RR 0.23; 95% CI 0.08-0.67; p = 0.007) in the early mobilization group. The incidence of CSF leak (RR 1.34; 95% CI 0.83-2.14; p = 0.23), hypotensive headache (RR 0.72; 95% CI 0.27-1.90; p = 0.50), additional repair surgery (RR 1.29; 95% CI 0.76-2.2; p = 0.35), and pseudomeningocele (RR 1.29; 95% CI 0.20-8.48; p = 0.79) did not differ significantly. In patients with incidental durotomy following spinal surgery, early mobilization was associated with a lower incidence of pulmonary complications as compared with prolonged bed rest. There was no significant difference between groups in terms of CSF leak, need for additional repair, pseudomeningocele, and hypotensive headache.

Microgravity-induced skeletal muscle atrophy in women and men: implications for long-duration spaceflights to the Moon and Mars.

The inclusion of women on spaceflights has historically been limited. Recently, the first woman who will travel to the Moon was selected, and more women are participating in long-duration spaceflights. However, physiological data from real and simulated microgravity exposure are limited in women. This investigation studied women (n = 8, 34 ± 1 yr) and men (n = 9, 32 ± 1 yr) who underwent 2 (women) or 3 (men) mo of simulated microgravity (6° head-down tilt bed rest). Quadriceps and triceps surae muscle volumes were assessed via MRI before bed rest, bed rest day 29 (BR29, women and men), bed rest day 57 (BR57, women), and bed rest day 89 (BR89, men). Volume of both muscle groups decreased (P < 0.05) in women and men at all bed rest timepoints. Quadriceps muscle volume loss in women was greater than men at 1 mo (BR29: -17% vs. -10%, P < 0.05) and this 1-mo loss for women was similar to men at 3 mo (BR89: -18%, P > 0.05). In addition, the loss in women at 2 mo (BR57: -21%) exceeded men at 3 mo (P < 0.05). For the triceps surae, there was a trend for greater muscle volume loss in women compared with men at 1 mo (BR29: -18% vs. -16%, P = 0.08), and loss in women at 2 mo was similar to men at 3 mo (BR57: -29%, BR89: -29%, P > 0.05). The collective evidence suggests that women experience greater lower limb muscle atrophy than men at least through the first 4 mo of microgravity exposure. More sex-specific microgravity studies are needed to help protect the health of women traveling on long-duration orbital and interplanetary spaceflights.NEW & NOTEWORTHY This study adds to the limited evidence regarding sex-specific responses to real or simulated microgravity exposure, which collectively suggests a sex-specific muscle atrophy profile, with women losing more than men at least through the first 4 mo of weightlessness. Considering the increase in women being selected for space missions, including the first women to travel to the Moon, more physiological data on women in response to microgravity are needed.

Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures.

INTRODUCTION: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. METHODS: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. RESULTS: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. CONCLUSION: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Brain Microstructure and Brain Function Changes in Space Headache by Head-Down-Tilted Bed Rest.

INTRODUCTION: Several astronauts have experienced severe headaches during spaceflight, but no studies have examined the associated brain microstructure and functional changes. Head-down-tilted bed rest (HDBR) is a well-established method for studying the physical effects of microgravity on the ground. In this study, we analyzed the changes in brain microstructure and function during headache caused by HDBR using diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging (R-fMRI).METHODS: We imaged 28 healthy subjects with DTI and R-fMRI in the horizontal supine position and HDBR. Using Tract-Based Spatial Statistics, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were compared between the headache and non-headache groups. Additionally, an analysis of functional connectivity (FC) was performed, followed by a correlation analysis between FC and numerical rating scale.RESULTS: HDBR caused headaches in 21 of 28 subjects. DTI analysis showed no significant change in fractional anisotropy after HDBR, whereas axial diffusivity, radial diffusivity, and mean diffusivity increased significantly. R-fMRI analysis showed a significant decrease in FC in several areas after HDBR. The headache group showed significantly higher FC before HDBR, and both groups showed higher FC after HDBR. Correlation analysis showed a positive correlation between FC and numerical rating scale before HDBR but negative after HDBR.DISCUSSION: We demonstrated the image change in the acute phase of space headache by HDBR using DTI and R-fMRI. Changes in brain microstructure and function specific to patients developing headaches may be evaluated by imaging.Goto M, Shibata Y, Ishiyama S, Matsumaru Y, Ishikawa E. Brain microstructure and brain function changes in space headache by head-down-tilted bed rest. Aerosp Med Hum Perform. 2023; 94(9):678-685.

Bed Rest as a Protective Factor for Subdural Hematoma in Spontaneous Intracranial Hypotension: A Retrospective Study.

BACKGROUND: Subdural hematoma (SDH) is a potentially life-threatening complication in patients with spontaneous intracranial hypotension (SIH). Though bed rest is the basis of conservative treatment, no clear evidence exists regarding the association between bed rest and the later complication of SDH in these patients. OBJECTIVES: This study aimed to evaluate the association between bed rest and SDH development in patients with SIH. STUDY DESIGN: A retrospective study was conducted from March 2013 through December 2019. Four hundred twenty adult patients diagnosed with SIH were enrolled. Clinical presentations and radiographic findings were recorded. The cumulative duration of bed rest in hours was used to measure the bed rest length. The clinical outcomes during follow-up were assessed. METHODS: Categorical data were compared using chi-square tests; continuous data were compared using the Mann-Whitney U test or Kruskal-Wallis test. A backwards stepwise Cox proportional hazard regression model adjusted with confounders which differed between SDH and non-SDH in univariate analysis was used to estimate the risk of cumulative duration of bed rest for SDH. A stratified Cox regression was performed to exclude the effect of the treatment algorithm. RESULTS: Of the 420 patients with SIH, 88 (21%) were in the SDH Group and 332 (79%) were in the non-SDH (NSDH) Group. The cumulative duration of bed rest in hours was a protective factor for SDH in SIH (Hazard Ratio [HR] = 0.997; P < 0.001). A stratified Cox regression analysis showed that the cumulative duration of bed rest remained a protective factor for SDH both in patients who received conservative treatment before admission (HR = 0.997; P < 0.001) and in those who did not (HR = 0.996; P = 0.061). Age (HR = 1.029, 95% CI, 1.009-1.050; P = 0.004) and orthostatic headache (HR = 4.770, 95% 95% CI, 2.177-10.450; P < 0.001) were risk factors for SDH in SIH. The clinical outcomes, including length of hospital stay, epidural blood patch (EBP) therapy, and repeated EBP therapy, were higher in the SDH Group. The revisit rate was similar between the 2 groups. LIMITATIONS: Retrospective studies are susceptible to different radiological procedures and therapeutic strategies. A bed rest score based on a patient's memory is susceptible to recognition and reporting bias. This is a single-center study and the sample size is not large. The validity of the bed rest scale has not been previously evaluated in any other study. CONCLUSIONS: Bed rest was a protective factor for SDH in patients with SIH. With more time and proper treatment, patients with SIH who have an SDH can achieve good prognosis in the long term.

Effects of daily artificial gravity training on orthostatic tolerance following 60-day strict head-down tilt bedrest.

PURPOSE: Orthostatic intolerance commonly occurs following immobilization or space flight. We hypothesized that daily artificial gravity training through short-arm centrifugation could help to maintain orthostatic tolerance following head-down tilt bedrest, which is an established terrestrial model for weightlessness. METHODS: We studied 24 healthy persons (eight women; age 33.3 ± 9.0 years; BMI 24.3 ± 2.1 kg/m2) who participated in the 60-days head-down tilt bedrest (AGBRESA) study. They were assigned to 30 min/day continuous or 6 × 5 min intermittent short-arm centrifugation with 1Gz at the center of mass or a control group. We performed head-up tilt testing with incremental lower-body negative pressure until presyncope before and after bedrest. We recorded an electrocardiogram, beat-to-beat finger blood pressure, and brachial blood pressure and obtained blood samples from an antecubital venous catheter. Orthostatic tolerance was defined as time to presyncope. We related changes in orthostatic tolerance to changes in plasma volume determined by carbon dioxide rebreathing. RESULTS: Compared with baseline measurements, supine and upright heart rate increased in all three groups following head-down tilt bedrest. Compared with baseline measurements, time to presyncope decreased by 323 ± 235 s with continuous centrifugation, by 296 ± 508 s with intermittent centrifugation, and by 801 ± 354 s in the control group (p = 0.0249 between interventions). The change in orthostatic tolerance was not correlated with changes in plasma volume. CONCLUSIONS: Daily artificial gravity training on a short-arm centrifuge attenuated the reduction in orthostatic tolerance after 60 days of head-down tilt bedrest.

High-intensity exercise does not protect against orthostatic intolerance following bedrest in 55- to 65-yr-old men and women.

Prolonged bedrest provokes orthostatic hypotension and intolerance of upright posture. Limited data are available on the cardiovascular responses of older adults to head-up tilt following bedrest, with no studies examining the potential benefits of exercise to mitigate intolerance in this age group. This randomized controlled trial of head-down bedrest (HDBR) in 55- to 65-yr-old men and women investigated if exercise could avert post-HDBR orthostatic intolerance. Twenty-two healthy older adults (11 female) underwent a strict 14-day HDBR and were assigned to either an exercise (EX) or control (CON) group. The exercise intervention included high-intensity, aerobic, and resistance exercises. Head-up tilt-testing to a maximum of 15 minutes was performed at baseline (Pre-Bedrest) and immediately after HDBR (R1), as well as 6 days (R6) and 4 weeks (R4wk) later. At Pre-Bedrest, three participants did not complete the full 15 minutes of tilt. At R1, 18 did not finish, with no difference in tilt end time between CON (422 ± 287 s) and EX (409 ± 346 s). No differences between CON and EX were observed at R6 or R4wk. At R1, just 1 participant self-terminated the test with symptoms, while 12 others reported symptoms only after physiological test termination criteria were reached. Finishers on R1 protected arterial pressure with higher total peripheral resistance relative to Pre-Bedrest. Cerebral blood velocity decreased linearly with reductions in arterial pressure, end-tidal CO2, and cardiac output. High-intensity interval exercise did not benefit post-HDBR orthostatic tolerance in older adults. Multiple factors were associated with the reduction in cerebral blood velocity leading to intolerance.

Effects of antioxidant supplementation on bone mineral density, bone mineral content and bone structure in healthy men during 60 days of 6° head-down tilt bed rest: Results from a randomised controlled trial.

Dietary countermeasures to mitigate detrimental spaceflight-induced effects on bone health would alleviate the requirements and the consequences imposed by other types of countermeasures for this risk. We hypothesised that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR), an analogue of spaceflight, would have a protective effect on bone mineral density (BMD), content (BMC) and bone structure parameters. An exploratory, randomised, controlled, single-blind intervention trial was conducted in a parallel design with 20 healthy male volunteers (age 34 ± 8 y, weight 74 ± 6 kg). The study included 14 days of baseline data collection (BDC) before bed rest, followed by 60 days of HDBR and a 14-day recovery period. Ten subjects in the antioxidant group received a supplement (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E and 80 µg/d selenium) daily. Ten subjects in the control group received no supplement. The diet was consistent with dietary reference intakes, individually tailored based on the subject's bodyweight and strictly controlled. We measured whole-body, lumbar spine and femur BMD and BMC, as well as BMD of the cortical and trabecular compartments of the distal radius and tibia, and cortical and trabecular thickness during BDC, HDBR and recovery. Data were analysed using linear mixed models. The supplementation of an antioxidant cocktail did not mitigate the deteriorating effects of HDBR on BMD, BMC and bone structure parameters. Our findings do not support a recommendation for antioxidant supplementation for astronauts.

Effects of time of bed rest on vascular complications after cardiac catheterization in pediatric patients with congenital heart disease: A randomized controlled trial.

BACKGROUND: Pediatric cardiac catheterization, which is performed by accessing the femoral vessel, requires immobilization and bed rest for 4-6 h to prevent vascular complications. Studies in adults suggest that the immobilization time for the same access can be safely reduced to approximately 2 h after catheterization. However, it is unclear whether bed-rest time can be safely decreased after catheterization in children. OBJECTIVE: To assess the effects of bed-rest duration on bleeding, vascular complications, pain level, and the use of additional sedatives after transfemoral cardiac catheterization in children with congenital heart disease. METHODS: This study was an open-label, randomized, controlled, posttest-only design, including 86 children who underwent cardiac catheterization. Children were allocated to receive either 2 h of bed rest (n = 42) in the experimental group or 4 h of bed rest (n = 42) in the control group following catheterization. RESULTS: The mean age of children was 3.93 (±3.82) years in the experimental group and 5.63 (±3.97) years in the control group. There was no difference in site bleeding incidence (P = 0.214), vascular complication score (P = 0.082), pain level (P = 0.445), or additional sedation use (P = 1.000) between the two groups. CONCLUSIONS: There were no significant hemostatic complications after 2 h of bed rest following pediatric catheterization; therefore, 2 h of bed rest was as safe as 4 h of bed rest. (Trial registration: KCT0007737).