Effect of trunk exercise upon lumbar IVD height and vertebral compliance when performed supine with 1 g at the CoM compared to upright in 1 g

Background: Spinal unloading in microgravity is associated with stature increments, back pain, intervertebral disc (IVD) swelling and impaired spinal kinematics. The aim of this study was to determine the effect of lateral stabilization, trunk rotation and isometric abdominal exercise upon lumbar IVD height, and both passive and active vertebral compliance when performed supine on a short-arm human centrifuge (SAHC)-a candidate microgravity countermeasure-with 1 g at the CoM, compared to that generated with equivalent upright exercise in 1 g. Methods: 12 (8 male) healthy subjects (33.8 ± 7 years, 178.4 ± 8.2 cm, 72.1 ± 9.6 kg) gave written informed consent. Subjects performed three sets of upper body trunk exercises either when standing upright (UPRIGHT), or when being spun on the SAHC. Lumbar IVD height and vertebral compliance (active and passive) were evaluated prior to SAHC (PRE SAHC) and following the first SAHC (POST SPIN 1) and second Spin (POST SPIN 2), in addition to before (PRE UPRIGHT), and after upright trunk exercises (POST UPRIGHT). Results: No significant effect upon IVD height (L2-S1) when performed UPRIGHT or on the SAHC was observed. Trunk muscle exercise induced significant (p < 0.05) reduction of active thoracic vertebral compliance when performed on the SAHC, but not UPRIGHT. However, no effect was observed in the cervical, lumbar or across the entire vertebral column. On passive or active vertebral compliance. Conclusion: This study, the first of its kind demonstrates that trunk exercise were feasible and tolerable. Whilst trunk muscle exercise appears to have minor effect upon IVD height, it may be a candidate approach to mitigate-particularly active-vertebral stability on Earth, and in μg via concurrent SAHC. However, significant variability suggests larger studies including optimization of trunk exercise and SAHC prescription with MRI are warranted. Trial registration: North Rhine ethical committee (Number: 6000223393) and registered on 29/09/2020 in the German Clinical Trials Register (DRKS00021750). Keywords: Artificial gravity; Countermeasures; Exercise; IVD; Spine; Stiffnes

A gravitational contribution to perceived body weight

The weightlessness experienced by astronauts has fascinated scientists and the public. On Earth, body weight is given by Newton's laws as mass times gravitational acceleration. That is, an object’s weight is determined by the pull of gravity on it. We hypothesised that perceived body weight is – like actual weight – dependent on the strength of gravity. If so, changes in the experienced strength of gravity should alter the experience of one’s own body weight. We asked participants to estimate the weight of two body parts, their hand or their head, both in normal terrestrial gravity (1g) and during exposure to experimentally altered gravitational fields, 0g and +1.8g during parabolic flight and +1g using a short arm human centrifuge. For both body parts, there was an increase in perceived weight during the experience of hypergravity, and a decrease during the experience of microgravity. Our results show that experimental alterations of gravity produce rapid changes in the perceived weight of specific individual body parts. Traditionally, research has focused on the social factors for weight perception, as in the putative role of mass media in eating disorders. Our results, in contrast, emphasize that the perception of body weight is highly malleable, and shaped by immediate sensory signals

Comparison of trunk muscle exercises in supine position during short arm centrifugation with 1 g at centre of mass and upright in 1 g

Spaceflight is associated with reduced antigravitational muscle activity, which results in trunk muscle atrophy and may contribute to post-flight postural and spinal instability. Exercise in artificial gravity (AG) performed via short-arm human centrifugation (SAHC) is a promising multi-organ countermeasure, especially to mitigate microgravity-induced postural muscle atrophy. Here, we compared trunk muscular activity (mm. rectus abdominis, ext. obliques and multifidi), cardiovascular response and tolerability of trunk muscle exercises performed during centrifugation with 1 g at individual center of mass on a SAHC against standard upright exercising. We recorded heart rate, blood pressure, surface trunk muscle activity, motion sickness and rating of perceived exertion (BORG) of 12 participants (8 male/4 female, 34 ± 7 years, 178.4 ± 8.2 cm, 72.1 ± 9.6 kg). Heart rate was significantly increased (p < 0.001) during exercises without differences in conditions. Systolic blood pressure was higher (p < 0.001) during centrifugation with a delayed rise during exercises in upright condition. Diastolic blood pressure was lower in upright (p = 0.018) compared to counter-clockwise but not to clockwise centrifugation. Target muscle activation were comparable between conditions, although activity of multifidi was lower (clockwise: p = 0.003, counter-clockwise: p < 0.001) and rectus abdominis were higher (clockwise: p = 0.0023, counter-clockwise: < 0.001) during centrifugation in one exercise type. No sessions were terminated, BORG scoring reflected a relevant training intensity and no significant increase in motion sickness was reported during centrifugation. Thus, exercising trunk muscles during centrifugation generates comparable targeted muscular and heart rate response and appears to be well tolerated. Differences in blood pressure were relatively minor and not indicative of haemodynamic challenge. SAHC-based muscle training is a candidate to reduce microgravity-induced inter-vertebral disc pathology and trunk muscle atrophy. However, further optimization is required prior to performance of a training study for individuals with trunk muscle atrophy/dysfunction

Impact of daily artificial gravity on autonomic cardiovascular control following 60-day head-down tilt bed rest

Impaired cardiovascular autonomic control following space flight or immobilization may limit the ability to cope with additional hemodynamic stimuli. Head-down tilt bedrest is an established terrestrial analog for space flight and offers the opportunity to test potential countermeasures for autonomic cardiovascular deconditioning. Previous studies revealed a possible benefit of daily artificial gravity on cardiovascular autonomic control following head-down tilt bedrest, but there is a need for efficiency in a long-term study before an artificial gravity facility would be brought to space. We hypothesized that artificial gravity through short-arm centrifugation attenuates functional adaptions of autonomic function during head-down tilt bed rest. 24 healthy persons (8 women, 33.4 ± 9.3 years, 24.3 ± 2.1 kg/m²) participated in the 60-day head-down tilt bed rest (AGBRESA) study. They were assigned to three groups, 30 min/day continuous, or 6(5 min intermittent short-arm centrifugation, or a control group. We assessed autonomic cardiovascular control in the supine position and in 5 minutes 80° head-up tilt position before and immediately after bed rest. We computed heart rate variability (HRV) in the time (rmssd) and frequency domain, blood pressure variability, and baroreflex sensitivity (BRS). RR interval corrected rmssd was reduced supine (p = 0.0358) and during HUT (p = 0.0161). Heart rate variability in the high-frequency band (hf-RRI; p = 0.0004) and BRS (p < 0.0001) decreased, whereas blood pressure variability in the low-frequency band (lf-SBP, p = 0.0008) increased following bedrest in all groups. We did not detect significant interactions between bedrest and interventions. We conclude that up to daily 30 min of artificial gravity on a short-arm centrifuge with 1Gz at the center of mass do not suffice to prevent changes in autonomic cardiovascular control following 60-day of 6° head-down tilt bed res

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

Insights into Current Tropomyosin Receptor Kinase (TRK) inhibitors: development and clinical application

The use of kinase-directed precision medicine has been heavily pursued since the discovery and development of imatinib. Annually, it is estimated that around ∼20 000 new cases of tropomyosin receptor kinase (TRK) cancers are diagnosed, with the majority of cases exhibiting a TRK genomic rearrangement. In this Perspective, we discuss current development and clinical applications for TRK precision medicine by providing the following: (1) the biological background and significance of the TRK kinase family, (2) a compilation of known TRK inhibitors and analysis of their cocrystal structures, (3) an overview of TRK clinical trials, and (4) future perspectives for drug discovery and development of TRK inhibitors