Standing Without Gravity: the Use of Lower Body Negative Pressure for Research and Reconditioning in Spaceflight

Weightlessness during spaceflight causes cephalad redistribution of intravascular and extravascular fluid, provoking cardiovascular and autonomic nervous system adaptations. The resulting functional state is appropriate for weightlessness but can result in orthostatic hypotension and intolerance during and after return to a persistent acceleration or gravitational environment. Lower body negative pressure (LBNP) applies subambient air pressure to the legs and lower abdomen inside a volume sealed at the waist, and decompression by 4050 mmHg reverses the spaceflightinduced cephalad shift. LBNP has been used both to test the state of cardiovascular system during spaceflight and as a countermeasure by all spacefaring nations. Two configurations have thus far been used in spaceflight since the first LBNP flew on the first Soviet Salyut station in 1971. The Soviet and Russian configuration, used in four Salyut stations, the Mir space station and the Russian segment of the International Space Station, has no saddle to support the body so during decompression the feet press against the bottom of the collapsible chamber which shortens and applies force against the feet proportional to the decompression level. Thus, activation of the skeletal musculature partially counteracts vascular and venous pooling in the enclosed body segments, stimulating the orthostatic compensatory mechanisms as they would be standing on Earth. In the American configuration, used aboard Skylab and the Space Shuttle, a saddle supported the astronaut so the feet did not contact the bottom of the chamber, and vascular engorgement was not countered by muscular contraction. This minimized skeletal muscle involvement, unmasked vascular compensatory mechanisms for research purposes, and allowed measurements of changes in leg volume and muscle sympathetic nerve activity. Both variants have demonstrated research and therapeutic value in appropriately designed protocols. LBNP continues to be used for research and countermeasures on ISS, and future versions may explore the value of exercise during LBNP as an integrated countermeasure. This paperwill review the history and development of LBNP for spaceflight research and therapeutic purposes

Aerobic Capacity Following Long Duration International Spaces Station (ISS) Missions: Preliminary Results

Maximum oxygen uptake (VO2max) is reduced immediately following space flights lasting 6%. WRmax also decreased on R+1/2 compared to preflight (Pre: 245+/-69, R+1/2: 210+/-45 W). On R+10, VO2max was 2.86+/-0.62 L(dot)/min, with 2 subjects still demonstrating a loss of > 6% from preflight. WRmax on R+10 was 240+/-49 W. HRmax did not change from pre to post-flight. Conclusions: These preliminary results, from the first 5 of 12 planned subjects of an ongoing ISS study, suggest that the majority of astronauts will experience a decrease in VO2max after long-duration space-flight. Interestingly, the two astronauts with the highest preflight VO2max had the greatest loss on R+1/2, and the astronaut with the lowest preflight VO2max increased by 13%. Thus, maintenance of VO2max may be more difficult in astronauts who have a high aerobic capacity, perhaps requiring more intense in-flight exercise countermeasure prescriptions

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

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Effects of six hours daily lower body negative pressure on orthostatic tolerance and cardiac performance during 30 days strict head-down tilt bedrest

Introduction: Orthostatic intolerance commonly occurs in astronauts returning to earth. Head-down tilt bedrest (HDTBR), which models cardiovascular adaptation to weightlessness, decreases orthostatic tolerance by 34–60% without any countermeasure. We hypothesized that daily six hours lower-body-negative-pressure (LBNP, - 25 mmHg) ameliorates orthostatic tolerance, plasma volume, and cardiovascular deconditioning during HDTBR. Methods: We submitted 23 healthy persons (12 women, 34.5 ± 9 years, 23.9 ± 2.8 kg/m²) to 30 days of strict HDTBR (SANS-CM study). Subjects were assigned to 6 h upright seating (positive control, n = 11) or - 25 mmHg LBNP (n = 12) per day. We measured left ventricular outflow tract diameter (LVOT) and LVOT-stroke volume by pulsed wave doppler echocardiography during 15 min of 80 head-up tilt testing (HUT) with incremental LBNP until presyncope before and after HDTBR. We determined plasma volume with CO-rebreathing two days before and at HDTBR day 27. Results: With HDTBR, orthostatic tolerance decreased 289 ± 89 s (- 23%) in the seated and 284 ± 95 s (- 22%) in the LBNP group (p\ 0.001 vs. baseline, p = 0.968 between groups). Plasma volume decreased 569 ± 114 ml in the seated and 604 ± 104 ml in the LBNP group (p\0.001 vs. baseline, p = 0.813 between groups). While supine stroke volume decreased 8 ± 1 ml in the seated and 9 ± 4 ml in the LBNP group (p\0.001 vs. baseline, p = 0.874 between groups), supine cardiac output did not change in either group. Both groups showed similar reductions in upright stroke volume following HDTBR, however, stroke volume at presyncope did not change with HDTBR. Conclusions: Six hours daily moderate intensity LBNP or seating did not fully attenuate orthostatic intolerance, plasma volume loss, or cardiovascular deconditioning during 30 days HDTBR. However, both interventions better maintained orthostatic tolerance compared with previous 30–60 days HDTBR studies without countermeasures

Effect of prior austenite grain size refinement by thermal cycling on the microstructural features of as-quenched lath martensite

Current trends in steels are focusing on refined martensitic microstructures to obtain high strength and toughness. An interesting manner to reduce the size of martensitic substructure is by reducing the size of the prior austenite grain (PAG). This work analyzes the effect of PAGS refinement by thermal cycling on different microstructural features of as-quenched lath martensite in a 0.3C-1.6Si-3.5Mn (wt pct) steel. The application of thermal cycling is found to lead to a refinement of the martensitic microstructures and to an increase of the density of high misorientation angle boundaries after quenching; these are commonly discussed to be key structural parameters affecting strength. Moreover, results show that as the PAGS is reduced, the volume fraction of retained austenite increases, carbides are refined and the concentration of carbon in solid solution as well as the dislocation density in martensite increase. All these microstructural modifications are related with the manner in which martensite forms from different prior austenite conditions, influenced by the PAGS.(OLD) MSE-