Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation.

Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures.

The effects of combined amplitude and high-frequency vibration on physically inactive osteopenic postmenopausal women.

Purpose: To evaluate whole-body vibration (WBV) osteogenic potential in physically inactive postmenopausal women using high-frequency and combined amplitude stimuli. Methods: Two-hundred fifty-five physically inactive postmenopausal women (55-75 years) with 10-year major osteoporotic fracture risk (3%-35%) participated in this 18-month study. For the first 12 months, the vibration group experienced progressive 20-min WBV sessions (up to 3 sessions/week) with rest periods (30-60 s) between exercises. Frequencies (30-50 Hz), with low (0.2-0.4 mm) and high (0.6-0.8 mm) amplitude stimuli were delivered via PowerPlate Pro5 platforms producing accelerations of (0.75-7.04 g). The last 6 months for the treatment group were a follow-up period similar to control. Serum bone remodelling markers [C-terminal crosslinked telopeptide of type-1 collagen (CTX), procollagen type-1 N-terminal propeptide (P1NP), bone alkaline phosphatase (BAP) and sclerostin] were measured at fasting. CTX and P1NP were determined by automated chemiluminescence immunoassay, bone alkaline phosphatase (BAP) by automated spectrophotometric immunoassay, and sclerostin by an enzyme-immunoassay. Bone mineral density (BMD) of the whole-body, proximal femur and lumbar vertebrae was measured by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture of the distal non-dominant radius and tibia was measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: Femoral neck (p = 0.520) and spine BMD (p = 0.444) failed to improve after 12 months of WBV. Bone macro and microstructural parameters were not impacted by WBV, as well as estimated failure load at the distal radius (p = 0.354) and tibia (p = 0.813). As expected, most DXA and HR-pQCT parameters displayed age-related degradation in this postmenopausal population. BAP and CTX increased over time in both groups, with CTX more marginally elevated in the vibration group when comparing baseline changes to month-12 (480.80 pmol/L; p = 0.039) and month-18 (492.78 pmol/L; p = 0.075). However, no differences were found when comparing group concentrations only at month-12 (506.35 pmol/L; p = 0.415) and month-18 (518.33 pmol/L; p = 0.480), indicating differences below the threshold of clinical significance. Overall, HR-pQCT, DXA bone parameters and bone turnover markers remained unaffected. Conclusion: Combined amplitude and high-frequency training for one year had no ameliorating effect on DXA and HR-pQCT bone parameters in physically inactive postmenopausal women. Serum analysis did not display any significant improvement in formation and resorption markers and also failed to alter sclerostin concentrations between groups.

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.

Evolution and function of the hominin forefoot.

The primate foot functions as a grasping organ. As such, its bones, soft tissues, and joints evolved to maximize power and stability in a variety of grasping configurations. Humans are the obvious exception to this primate pattern, with feet that evolved to support the unique biomechanical demands of bipedal locomotion. Of key functional importance to bipedalism is the morphology of the joints at the forefoot, known as the metatarsophalangeal joints (MTPJs), but a comprehensive analysis of hominin MTPJ morphology is currently lacking. Here we present the results of a multivariate shape and Bayesian phylogenetic comparative analyses of metatarsals (MTs) from a broad selection of anthropoid primates (including fossil apes and stem catarrhines) and most of the early hominin pedal fossil record, including the oldest hominin for which good pedal remains exist, Ardipithecus ramidus Results corroborate the importance of specific bony morphologies such as dorsal MT head expansion and "doming" to the evolution of terrestrial bipedalism in hominins. Further, our evolutionary models reveal that the MT1 of Ar. ramidus shifts away from the reconstructed optimum of our last common ancestor with apes, but not necessarily in the direction of modern humans. However, the lateral rays of Ar. ramidus are transformed in a more human-like direction, suggesting that they were the digits first recruited by hominins into the primary role of terrestrial propulsion. This pattern of evolutionary change is seen consistently throughout the evolution of the foot, highlighting the mosaic nature of pedal evolution and the emergence of a derived, modern hallux relatively late in human evolution.

Form and function of the human and chimpanzee forefoot: implications for early hominin bipedalism.

During bipedal walking, modern humans dorsiflex their forefoot at the metatarsophalangeal joints (MTPJs) prior to push off, which tightens the plantar soft tissues to convert the foot into a stiff propulsive lever. Particular features of metatarsal head morphology such as "dorsal doming" are thought to facilitate this stiffening mechanism. In contrast, chimpanzees are believed to possess MTPJ morphology that precludes high dorsiflexion excursions during terrestrial locomotion. The morphological affinity of the metatarsal heads has been used to reconstruct locomotor behavior in fossil hominins, but few studies have provided detailed empirical data to validate the assumed link between morphology and function at the MTPJs. Using three-dimensional kinematic and morphometric analyses, we show that humans push off with greater peak dorsiflexion angles at all MTPJs than do chimpanzees during bipedal and quadrupedal walking, with the greatest disparity occurring at MTPJ 1. Among MTPJs 2-5, both species exhibit decreasing peak angles from medial to lateral. This kinematic pattern is mirrored in the morphometric analyses of metatarsal head shape. Analyses of Australopithecus afarensis metatarsals reveal morphology intermediate between humans and chimpanzees, suggesting that this species used different bipedal push-off kinematics than modern humans, perhaps resulting in a less efficient form of bipedalism.

Functional aspects of metatarsal head shape in humans, apes, and Old World monkeys.

Modern human metatarsal heads are typically described as "dorsally domed," mediolaterally wide, and dorsally flat. Despite the apparent functional importance of these features in forefoot stability during bipedalism, the distinctiveness of this morphology has not been quantitatively evaluated within a broad comparative framework. In order to use these features to reconstruct fossil hominin locomotor behaviors with any confidence, their connection to human bipedalism should be validated through a comparative analysis of other primates with different locomotor behaviors and foot postures, including species with biomechanical demands potentially similar to those of bipedalism (e.g., terrestrial digitigrady). This study explores shape variation in the distal metatarsus among humans and other extant catarrhines using three-dimensional geometric morphometrics (3 DGM). Shape differences among species in metatarsal head morphology are well captured by the first two principal components of Procrustes shape coordinates, and these two components summarize most of the variance related to "dorsal doming" and "dorsal expansion." Multivariate statistical tests reveal significant differences among clades in overall shape, and humans are reliably distinguishable from other species by aspects of shape related to a greater degree of dorsal doming. Within quadrupeds, terrestrial species also trend toward more domed metatarsal heads, but not to the extent seen in humans. Certain aspects of distal metatarsus shape are likely related to habitual dorsiflexion of the metatarsophalangeal joints, but the total morphological pattern seen in humans is distinct. These comparative results indicate that this geometric morphometric approach is useful to characterize the complexity of metatarsal head morphology and will help clarify its relationship with function in fossil primates, including early hominins.