Six-day dry immersion leads to downregulation of slow-fiber type and mitochondria-related genes expression.

The soleus muscle in humans is responsible for maintaining an upright posture and participating in walking and running. Under muscle disuse, it undergoes molecular signaling changes that result in altered force and work capacity. The triggering mechanisms and pathways of these changes are not yet fully understood. In this article, we aimed to detect the molecular pathways that are involved in the unloading-induced alterations in the human soleus muscle under 6-days of dry immersion. A 6-day dry immersion led to the downregulation of mitochondrial biogenesis and dynamics markers, upregulation of calcium-dependent CaMK II phosphorylation, enhanced PGC1α promoter region methylation, and altered muscle micro-RNA expression, without affecting p-AMPK content or fiber-type transformation.NEW & NOTEWORTHY Dry immersion dysregulates mitochondrial genes expression, affects mi-RNA expression and PGC1 promoter methylation.

Corticospinal excitability after 5-day Dry Immersion in women.

In light of the development of manned astronautics and the increasing participation of women in space flights, the question of female body adaptation to microgravity conditions becomes relevant. Currently, one of the important directions in this issue is to study the effects of support withdrawal as a factor of weightlessness on the human sensorimotor system. Dry Immersion is one of the well-known ground-based models, which adequately reproduces the main physiological effects of space flight. The aim of this study was to evaluate the changes in motor evoked potentials of the lower leg gravity-dependent muscles in women after a 5-day Dry Immersion. We analyzed evoked responses to transcranial and trans-spinal magnetic stimulation. In this method, areas of interest (the motor cortex and lumbosacral thickening of the spinal cord) are stimulated with an electromagnetic stimulus. The experiment was conducted with the participation of 16 healthy female volunteers with a natural menstrual cycle. The thresholds, amplitudes, and latencies of motor potentials evoked by magnetic stimulation were assessed. We showed that 5-day exposure to support withdrawal leads to a decrease in motor-evoked potential thresholds and central motor conduction time, although changes in motor response amplitudes were ambiguous. The data obtained correspond to the results of previous research on Dry Immersion effects on the sensorimotor system in men.

Corrigendum: Impact of different ground-based microgravity models on human sensorimotor system.

[This corrects the article DOI: 10.3389/fphys.2023.1085545.].

[Potential use of thermoneutral «dry immersion¼ in oncological rehabilitation]. / Potentsial'noe ispol'zovanie termoneitral'noi «sukhoi immersii¼ v onkoreabilitatsii.

OBJECTIVE: To conduct an analytical review of the available literature data on thermoneutral «dry immersion¼ (TSI) - a method that simulates the state of weightlessness/microgravity. MATERIAL AND METHODS: The review included data from electronic databases: Scopus, Web of Science, MedLine, Wiley, World Health Organization, The Cochrane Central Register of Controlled Trials, ScienceDirect, PubMed, elibrary, CyberLeninka, disserCat. RESULTS: The extensive database of in vitro studies contains information on the reduction of cell proliferation, invasion, migration and increased apoptosis of thyroid, breast, lung, stomach, colon cancer cells, Hodgkin's lymphoma, glioblastoma, leukemia, melanoma, osteosarcoma of a human under the influence of microgravity. The vast majority of works are devoted to experiments on healthy people to finding out the mechanisms of action of long-term continuous microgravity. The study of the therapeutic effect of TSI as a physiotherapeutic procedure of one or repeated sessions was carried out by individual authors. Positive results of a short stay in the unsupported model were obtained in the treatment of children with perinatal disorders, cerebral palsy, patients with hypertension in a state of hypertensive crisis, Parkinson's disease, skin burn II gr. The results of the analytical review provide an opportunity to begin scientific research on the effectiveness and safety of thermoneutral «dry immersion¼ in the complex rehabilitation of cancer patients.

Perception of length and orientation in dry immersion.

Introduction: How does gravity (or lack thereof) affect sensory-motor processing? We analyze sensorimotor estimation dynamics for line segments with varying direction (orientation) in a 7-day dry immersion (DI), a ground-based model of gravitational unloading. Methods: The measurements were carried out before the start of the DI, on the first, third, fifth and seventh days of the DI, and after its completion. At the memorization stage, the volunteers led the leading hand along the visible segment on a touchscreen display, and at the reproduction stage they repeated this movement on an empty screen. A control group followed the same procedure without DI. Results: Both in the DI and control groups, when memorizing, the overall error in estimating the lengths and directions of the segments was small and did not have pronounced dynamics; when reproducing, an oblique effect (higher variability of responses to oblique orientations compared to cardinal ones) was obtained. We then separated biases (systematic error) and uncertainty (random error) in subjects' responses. At the same time, two opposite trends were more pronounced in the DI group during the DI. On the one hand the cardinal bias (a repulsion of orientation estimates away from cardinal axes) and, to a small extent, the variability of direction estimates decreased. On the other hand, the overestimation bias in length estimates increased. Discussion: Such error pattern strongly supports the hypotheses of the vector encoding, in which the direction and length of the planned movement are encoded independently of each other when the DI disrupts primarily the movement length encoding.

Cerebral Circulation and Brain Temperature during an Ultra-Short Session of Dry Immersion in Young Subjects.

The primary aim of the study was to assess cerebral circulation in healthy young subjects during an ultra-short (45 min) session of ground-based microgravity modeled by "dry" immersion (DI), with the help of a multifunctional Laser Doppler Flowmetry (LDF) analyzer. In addition, we tested a hypothesis that cerebral temperature would grow during a DI session. The supraorbital area of the forehead and forearm area were tested before, within, and after a DI session. Average perfusion, five oscillation ranges of the LDF spectrum, and brain temperature were assessed. Within a DI session, in the supraorbital area most of LDF parameters remained unchanged except for a 30% increase in respiratory associated (venular) rhythm. The temperature of the supraorbital area increased by up to 38.5 °C within the DI session. In the forearm area, the average value of perfusion and its nutritive component increased, presumably due to thermoregulation. In conclusion, the results suggest that a 45 min DI session does not exert a substantial effect on cerebral blood perfusion and systemic hemodynamics in young healthy subjects. Moderate signs of venous stasis were observed, and brain temperature increased during a DI session. These findings must be thoroughly validated in future studies because elevated brain temperature during a DI session can contribute to some reactions to DI.

Impact of different ground-based microgravity models on human sensorimotor system.

This review includes current and updated information about various ground-based microgravity models and their impact on the human sensorimotor system. All known models of microgravity are imperfect in a simulation of the physiological effects of microgravity but have their advantages and disadvantages. This review points out that understanding the role of gravity in motion control requires consideration of data from different environments and in various contexts. The compiled information can be helpful to researchers to effectively plan experiments using ground-based models of the effects of space flight, depending on the problem posed.

Striated Muscle Evaluation Based on Velocity and Amortization Ratio of Mechanical Impulse Propagation in Simulated Microgravity Environment.

Long-duration space flight missions impose extreme physiological stress and/or changes, such as musculoskeletal function degradation, on the crew due to the microgravity exposure. A great deal of research studies have been conducted in order to understand these physiological stress influences and to provide countermeasures to minimize the observed negative effects of weightlessness exposure on musculoskeletal function. Among others, studies and experiments have been conducted in DI analogue Earth-based facilities in order to reproduce the weightlessness negative effects on the human body. This paper presents a complex muscular analysis of mechanical wave propagation in striated muscle, using MusTone, a device developed in-house at the Institute of Space Science, Romania. The data were collected during a 21-day DI campaign in order to investigate muscle fibers' behavior in longitudinal direction, after applying a mechanical impulse, taking into account two particular parameters, namely propagation velocity and amortization ratio. The parameters were determined based on the wave-propagation data collected from five points (one impact point, two distal direction points, and two proximal direction points) along the muscle fiber. By statistically analyzing propagation velocity and amortization ratio parameters, the study revealed that muscle deconditioning is time dependent, the amortization ratio is more significant in the distal direction, and the lower fibers are affected the most.

4 days in dry immersion increases arterial wall response to ultrasound wave as measured using radio-frequency signal, comparison with spaceflight data.

Recent studies have reported a significant increase in common carotid artery (CCA) intima media thickness, wall stiffness and reflectivity to ultrasound, in astronauts, after six months of spaceflight. The hypothesis was that 4 days in dry immersion (subjects under bags of water) will be sufficient to change the CCA wall reflectivity to ultrasound similar to what observed after spaceflight. Such response would be quantified using the amplitude of the ultrasound signal returned to the probe by the target concerned. [coefficient of signal return (Rs)]. The Rs for anterior and posterior CCA wall, sternocleidomastoid muscle, intima layer and CCA lumen were calculated from the ultrasound radio frequency (RF) data displayed along each echographic line. After four days of DI, Rs increased in the CCA posterior wall (+15% +/- 10 from pre DI, p < 0.05), while no significant change was observed in the other targets. The observed increase in Rs with DI was approximately half compared to what was observed after six months of space flight (+34% +/- 14). This difference may be explained by dose response (dry immersion only four days in duration). As a marker of tissue-level physical changes, Rs provide complimentary information alongside previously observed CCA wall thickness and stiffness.

Dry immersion induced acute low back pain and its relationship with trunk myofascial viscoelastic changes.

Microgravity induces spinal elongation and Low Back Pain (LBP) but the pathophysiology is unknown. Changes in paraspinal muscle viscoelastic properties may play a role. Dry Immersion (DI) is a ground-based microgravity analogue that induces changes in m. erector spinae superficial myofascial tissue tone within 2 h. This study sought to determine whether bilateral m. erector spinae tone, creep, and stiffness persist beyond 2 h; and if such changes correlate with DI-induced spinal elongation and/or LBP. Ten healthy males lay in the DI bath at the Institute of Biomedical Problems (Moscow, Russia) for 6 h. Bilateral lumbar (L1, L4) and thoracic (T11, T9) trunk myofascial tone, stiffness and creep (MyotonPRO), and subjective LBP (0-10 NRS) were recorded before DI, after 1h, 6 h of DI, and 30min post. The non-standing spinal length was evaluated on the bath lifting platform using a bespoke stadiometer before and following DI. DI significantly modulated m. erector spinae viscoelastic properties at L4, L1, T11, and T9 with no effect of laterality. Bilateral tissue tone was significantly reduced after 1 and 6 h DI at L4, L1, T11, and T9 to a similar extent. Stiffness was also reduced by DI at 1 h but partially recovered at 6 h for L4, L1, and T11. Creep was increased by DI at 1 h, with partial recovery at 6 h, although only T11 was significant. All properties returned to baseline 30 min following DI. Significant spinal elongation (1.17 ± 0.20 cm) with mild (at 1 h) to moderate (at 6 h) LBP was induced, mainly in the upper lumbar and lower thoracic regions. Spinal length increases positively correlated (Rho = 0.847, p = 0.024) with middle thoracic (T9) tone reduction, but with no other stiffness or creep changes. Spinal length positively correlated (Rho = 0.557, p = 0.039) with Max LBP; LBP failed to correlate with any m. erector spinae measured parameters. The DI-induced bilateral m. erector spinae tone, creep, and stiffness changes persist beyond 2 h. Evidence of spinal elongation and LBP allows suggesting that the trunk myofascial tissue changes could play a role in LBP pathogenesis observed in real and simulated microgravity. Further study is warranted with longer duration DI, assessment of IVD geometry, and vertebral column stability.

Gait Characteristics Analyzed with Smartphone IMU Sensors in Subjects with Parkinsonism under the Conditions of "Dry" Immersion.

Parkinson's disease (PD) is increasingly being studied using science-intensive methods due to economic, medical, rehabilitation and social reasons. Wearable sensors and Internet of Things-enabled technologies look promising for monitoring motor activity and gait in PD patients. In this study, we sought to evaluate gait characteristics by analyzing the accelerometer signal received from a smartphone attached to the head during an extended TUG test, before and after single and repeated sessions of terrestrial microgravity modeled with the condition of "dry" immersion (DI) in five subjects with PD. The accelerometer signal from IMU during walking phases of the TUG test allowed for the recognition and characterization of up to 35 steps. In some patients with PD, unusually long steps have been identified, which could potentially have diagnostic value. It was found that after one DI session, stepping did not change, though in one subject it significantly improved (cadence, heel strike and step length). After a course of DI sessions, some characteristics of the TUG test improved significantly. In conclusion, the use of accelerometer signals received from a smartphone IMU looks promising for the creation of an IoT-enabled system to monitor gait in subjects with PD.

DI-5-Cuffs: Bone Remodelling and Associated Metabolism Markers in Humans After Five Days of Dry Immersion to Simulate Microgravity.

Background: The dry immersion (DI) model closely reproduces factors of spaceflight environment such as supportlessness, mechanical and axial unloading, physical inactivity, and induces early increased bone resorption activity and metabolic responses as well as fluid centralization. The main goal of this experiment was to assess the efficacity of venoconstrictive thigh cuffs, as countermeasure to limit cephalad fluidshift, on DI-induced deconditioning, in particular for body fluids and related ophthalmological disorders. Our specific goal was to deepen our knowledge on the DI effects on the musculoskeletal events and to test whether intermittent counteracting fluid transfer would affect DI-induced bone modifications. Methods: Eighteen males divided into Control (DI) or Cuffs (DI-TC) group underwent an unloading condition for 5 days. DI-TC group wore thigh cuffs 8-10 h/day during DI period. Key markers of bone turnover, phospho-calcic metabolism and associated metabolic factors were measured. Results: In the DI group, bone resorption increased as shown by higher level in Tartrate-resistant acid phosphatase isoform 5b at DI24h. C-terminal telopeptide levels were unchanged. Bone formation and mineralization were also affected at DI24h with a decreased in collagen type I synthesis and an increased bone-specific alkaline phosphatase. In addition, osteocalcin and periostin levels decreased at DI120h. Calcemia increased up to a peak at DI48h, inducing a trend to decrease in parathyroid hormone levels at DI120h. Phosphatemia remained unchanged. Insulin-like growth factor 1 and visfatin were very sensitive to DI conditions as evidenced by higher levels by 120% vs. baseline for visfatin at DI48h. Lipocalin-2, a potential regulator of bone homeostasis, and irisin were unchanged. The changes in bone turnover markers were similar in the two groups. Only periostin and visfatin changes were, at least partially, prevented by thigh cuffs. Conclusion: This study confirmed the rapid dissociation between bone formation and resorption under DI conditions. It revealed an adaptation peak at DI48h, then the maintenance of this new metabolic state during all DI. Notably, collagen synthesis and mineralisation markers evolved asynchronously. Thigh cuffs did not prevent significantly the DI-induced deleterious effects on bone cellular activities and/or energy metabolism.

NAIAD-2020: Characteristics of Motor Evoked Potentials After 3-Day Exposure to Dry Immersion in Women.

As female astronauts participate in space flight more and more frequently, there is a demand for research on how the female body adapts to the microgravity environment. In particular, there is very little research on how the neuromuscular system reacts to gravitational unloading in women. We aimed to estimate changes in motor evoked potentials (MEPs) in the lower leg muscles in women after 3-day exposure to Dry Immersion (DI), which is one of the most widely used ground models of microgravity. Six healthy female volunteers (mean age 30.17 ± 5.5 years) with a natural menstrual cycle participated in this experiment. MEPs were recorded from the gastrocnemius and soleus muscles twice before DI, on the day of DI completion, and 3 days after DI, during the recovery period. To evoke motor responses, transcranial and trans-spinal magnetic stimulation was applied. We showed that changes in MEP characteristics after DI exposure were different depending on the stimulation site, but were similar for both muscles. For trans-spinal stimulation, MEP thresholds decreased compared to baseline values, and amplitudes, on the contrary, increased, resembling the phenomenon of hypogravitational hyperreflexia. This finding is in line with data observed in other experiments on both male and female participants. MEPs to transcranial stimulation had an opposing dynamic, which may have resulted from the small group size and large inter-subject variability, or from hormonal fluctuations during the menstrual cycle. Central motor conduction time remained unchanged, suggesting that pyramidal tract conductibility was not affected by DI exposure. More research is needed to explore the underlying mechanisms.

Reduced Regional Cerebral Blood Flow Measured by 99mTc-Hexamethyl Propylene Amine Oxime Single-Photon Emission Computed Tomography in Microgravity Simulated by 5-Day Dry Immersion.

Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF. Around 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n=9) or cuffs (n=9) group. rCBF was measured 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, p uncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, p uncorr<0.001), bilateral insula (right insula peak level: 4.10, p uncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, p uncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.

Sleep in 21-Day Dry Immersion. Are Cardiovascular Adjustments Rapid Eye Movement Sleep-Dependent?

Introduction: A decrease in sleep quality and duration during space missions has repeatedly been reported. However, the exact causes that underlie this effect remain unclear. In space, sleep might be impacted by weightlessness and its influence on cardiovascular function. In this study, we aimed at exploring the changes of night sleep architecture during prolonged, 21-day Dry Immersion (DI) as one of the ground-based models for microgravity studies and comparing them with adaptive changes in the cardiovascular system. Methods: Ten healthy young men were exposed to DI for 21 days. The day before (baseline, B-1), on the 3rd (DI3), 10th (DI10), and 19th (DI19) day of DI, as well as in the recovery period, 1 day after the end of DI (R + 1), they were subjected to overnight polysomnography (PSG) and ambulatory blood pressure monitoring. Results: On DI3, when the most severe back pain occurred due to the effects of DI on the spine and back muscles, the PSG data showed dramatically disorganized sleep architecture. Sleep latency, the number of awakenings, and the duration of wake after sleep onset (WASO) were significantly increased compared with the B-1. Furthermore, the sleep efficiency, duration of rapid eye movement sleep (REM), and duration of non-rapid eye movement stage 2 decreased. On DI10, subjective pain ratings declined to 0 and sleep architecture returned to the baseline values. On DI19, the REM duration increased and continued to rise on R + 1. An increase in REM was accompanied by rising in a nighttime heart rate (HR), which also shows the most significant changes after the end of DI. On DI19 and R + 1, the REM duration showed opposite correlations with the BP parameters: on DI19 it was negatively associated with the systolic BP (SBP), and on R + 1 it was positively correlated with the diastolic BP (DBP). Conclusion: An increase in REM at the end of DI and in recovery might be associated with regulatory changes in the cardiovascular system, in particular, with the reorganization of the peripheral and central blood flow in response to environmental changes.

Early Deconditioning of Human Skeletal Muscles and the Effects of a Thigh Cuff Countermeasure.

Muscle deconditioning is a major consequence of a wide range of conditions from spaceflight to a sedentary lifestyle, and occurs as a result of muscle inactivity, leading to a rapid decrease in muscle strength, mass, and oxidative capacity. The early changes that appear in the first days of inactivity must be studied to determine effective methods for the prevention of muscle deconditioning. To evaluate the mechanisms of muscle early changes and the vascular effect of a thigh cuff, a five-day dry immersion (DI) experiment was conducted by the French Space Agency at the MEDES Space Clinic (Rangueil, Toulouse). Eighteen healthy males were recruited and divided into a control group and a thigh cuff group, who wore a thigh cuff at 30 mmHg. All participants underwent five days of DI. Prior to and at the end of the DI, the lower limb maximal strength was measured and muscle biopsies were collected from the vastus lateralis muscle. Five days of DI resulted in muscle deconditioning in both groups. The maximal voluntary isometric contraction of knee extension decreased significantly. The muscle fiber cross-sectional area decreased significantly by 21.8%, and the protein balance seems to be impaired, as shown by the reduced activation of the mTOR pathway. Measurements of skinned muscle fibers supported these results and potential changes in oxidative capacity were highlighted by a decrease in PGC1-α levels. The use of the thigh cuff did not prevent muscle deconditioning or impact muscle function. These results suggest that the major effects of muscle deconditioning occur during the first few days of inactivity, and countermeasures against muscle deconditioning should target this time period. These results are also relevant for the understanding of muscle weakness induced by muscle diseases, aging, and patients in intensive care.

Autonomic Function in Parkinson's Disease Subjects Across Repeated Short-Term Dry Immersion: Evidence From Linear and Non-linear HRV Parameters.

Several studies have shown that "dry" immersion appears as a promising method of rehabilitation for Parkinson's disease. Still, little is known about the cardiovascular reaction in "dry" immersion (DI), especially in Parkinson's disease (PD). Therefore, this study was aimed to evaluate the effect of repeated 45-min DI sessions on autonomic function in subjects with PD. The study group consisted of 20 subjects with PD [13 men, seven women, aged 51-66 years old, Hoehn & Yahr (H&Y) staged 1-3] were enrolled in the study according to inclusion and non-inclusion criteria. The DI program was comprised of seven 45-min DI sessions, applied within 25-30 days. Blood pressure (BP), heart rate (HR), and electrocardiogram (ECG) in the standard lead II were recorded at 1st, 4th, and 7th DI, before, on the 15, 30, and 40th min of DI session. Autonomic function was assessed with analysis of heart rate variability (HRV) using Kubios Standard version 2 software. Linear (time- and frequency-domain) and non-linear (correlation dimension, entropies, DFA1 and DFA2, percent of determinism, and recurrence) were computed. At baseline condition, time- and frequency-domain HRV parameters showed low variability of HR, which indicates reduced autonomic neurogenic control of HR. Throughout the DI session, systolic and diastolic BP has decreased by 5-7 mm Hg (p < 0.001), and time- and frequency-domain parameters of HRV have significantly increased, what can be regarded as compensatory mechanisms of hemodynamics during DI. The structure of the regulatory input to the heart seen by HRV was characterized by low complexity and reduced autonomic neurogenic control of HR. Across the program of DI sessions, the hypotensive effect was documented, but no notable modification of the HRV-parameters was found. The absence of long-term modification of the studied parameters can be attributed both to deconditioning environmental effect of DI and limited adaptation of the organism due to neurodegeneration in PD. That should be taken into consideration when planning rehabilitation measures in subjects of older age and chronic somatic diseases with modeled microgravity.

Effects of Venoconstrictive Thigh Cuffs on Dry Immersion-Induced Ophthalmological Changes.

Neuro-ophthalmological changes named spaceflight associated neuro-ocular syndrome (SANS) reported after spaceflights are important medical issues. Dry immersion (DI), an analog to microgravity, rapidly induces a centralization of body fluids, immobilization, and hypokinesia similar to that observed during spaceflight. The main objectives of the present study were 2-fold: (1) to assess the neuro-ophthalmological impact during 5 days of DI and (2) to determine the effects of venoconstrictive thigh cuffs (VTC), used as a countermeasure to limit headward fluid shift, on DI-induced ophthalmological adaptations. Eighteen healthy male subjects underwent 5 days of DI with or without VTC countermeasures. The subjects were randomly assigned into two groups of 9: a control and cuffs group. Retinal and optic nerve thickness were assessed with spectral-domain optical coherence tomography (OCT). Optic nerve sheath diameter (ONSD) was measured by ocular ultrasonography and used to assess indirect changes in intracranial pressure (ICP). Intraocular pressure (IOP) was assessed by applanation tonometry. A higher thickness of the retinal nerve fiber layer (RNFL) in the temporal quadrant was observed after DI. ONSD increased significantly during DI and remained higher during the recovery phase. IOP did not significantly change during and after DI. VTC tended to limit the ONSD enlargement but not the higher thickness of an RNFL induced by DI. These findings suggest that 5 days of DI induced significant ophthalmological changes. VTC were found to dampen the ONSD enlargement induced by DI.