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The purpose of this study was to quantify the effects of loaded backpacks on shoulder muscle oxygenation, skin blood flow, and pain. We hypothesized that backpack load carriage is associated with lower shoulder muscle oxygenation and skin microvascular flow. Near-infrared spectroscopy quantified shoulder tissue oxygenation and laser Doppler flow measured skin microvascular flow. Eight adult volunteers donned a standard backpack without added load, 5 kg load, and 10 kg load for 5 min while standing. An 8 min rest period before each backpack donning condition ensured that all measured parameters returned to baseline. Data were analyzed using a repeated measures ANOVA and significance set at p < 0.05. Donning a 10 kg backpack significantly reduced shoulder muscle oxygenation by 22 ± 23% as compared to the empty backpack control condition (p = 0.023). In addition, a 10 kg backpack load reduced skin microvascular flow by 82 ± 22%, as compared to the empty backpack control condition (p = 0.024). Perceived pain was significantly higher when wearing the 10 kg backpack (level 4 on a 10-maximal pain scale) as compared to the empty backpack (0, 0–no pain) (p < 0.05). In conclusion, backpack loads of 10 kg decrease shoulder muscle oxygenation and skin microvascular flow. [ABSTRACT FROM AUTHOR]

Abstract: Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded tibia had lost 78% of its trabecular contents. At this time-point, the rats received bilateral proximal tibiae screw implants. Ten of the 20 rats were given daily injections of 5μg/kg PTH (1–34). After two weeks of healing, screw fixation was measured by pull-out, and microCT of the distal femur cancellous compartment was performed. Pull-out force provided an estimate for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30N), but increased it by less than half in the loaded ones (from 30 to 44N). In relative terms, PTH had a stronger effect on pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest that PTH treatment for stimulation of bone healing does not require simultaneous mechanical stimulation. [Copyright &y& Elsevier]

R5373 --> 603.16 --> Introduction: Weightlessness during spaceflight causes a chronic cephalad fluid shift that has been hypothesized to underlie numerous risks associated with spaceflight, including the development of ocular structural and functional changes and in rare cases venous thrombosis. Acute use of 25 mmHg lower body negative pressure (LBNP) during spaceflight can partially reverse this headward fluid shift and thus, may represent a promising countermeasure. However, there are limited data on how the cardiovascular system responds to sustained use of mild LBNP during spaceflight when cardiovascular deconditioning and adaptation may cause crewmembers to be more susceptible to orthostatic stressors than they would have been on Earth. Purpose: The purpose of this study was to quantify the heart rate (HR) and blood pressure response throughout ~60 minutes of exposure to 25 mmHg LBNP during spaceflight and determine if this response was augmented at later time points during 6‐month spaceflight missions. Hypothesis: We hypothesized that crewmembers would experience an increase in HR during LBNP that would be sufficient to maintain mean arterial pressure (MAP) and this would not be augmented later in spaceflight. Methods: Brachial arterial pressure and HR were measured before and throughout ~60 min of 25 mmHg LBNP after ~45 days (FD45) and ~150 days (FD150) of spaceflight in 12 crewmembers. Total LBNP session times varied slightly due to logistical constraints. MAP and HR changes from baseline with LBNP exposure were analyzed with splines models. Marginal means were used for estimation and statistical comparisons across time and between flight days. Results: Before LBNP use, HR was 59 beats per min (BPM 95% CI: 56 – 62) and MAP was 93 mmHg (95% CI: 90 – 96). During LBNP exposure on FD45, HR increased by 9 BPM (95% CI: +7 – +10) at 15 min of exposure, and increased further to +10 BPM (95% CI: +8 – +12) at 30 min, and +11 BPM (95% CI: +9 – +14) at 45 min. On FD150, HR increased by 8 BPM (95% CI: +5 – +11) at 15 min of exposure but plateaued thereafter. MAP decreased by 5 mmHg (95% CI: ‐8 – ‐2) at 15 min and remained lower thereafter. MAP responses during ~60 min of LBNP exposure were not statistically different between FD45 and FD150. A total of 46 sessions of LBNP were successfully completed, and only a single case of mild hypotensive symptoms was reported, and this session was completed. Conclusion: These data suggest that the cardiovascular system can accommodate up to 60 min of sustained use of mild levels of LBNP during long‐duration spaceflight. There was a single report of mild hypotensive symptoms during use of LBNP by an individual who had low blood pressure prior to the start of the LBNP session. Thus, the absolute arterial blood pressure should be taken into consideration when determining if an LBNP session will be a potential challenge to the cardiovascular system during spaceflight. [ABSTRACT FROM AUTHOR]

Abstract: The Sost gene encodes Sclerostin, an inhibitor of Wnt-signaling, generally considered a main response gene to mechanical loading in bone. Several papers describe that unloading leads to upregulation of Sost, which in turn may lead to loss of bone. These studies were based on whole bone homogenates or cortical bone. By serendipity, we noted an opposite response to unloading in the proximal rat tibia. Therefore, we hypothesized that Sost-expression in response to changes in mechanical load is bone site specific. One hind limb of male, 3 month old rats was unloaded by paralyzing the extensors with Botulinium toxin A (Botox) injections. A series of experiments compared the expression of Sost mRNA in the unloaded and contralateral, loaded limbs, after 3 or 10 days, in metaphyseal cancellous bone, metaphyseal cortical bone, and diaphyseal cortical bone. We also conducted μCT to confirm changes in bone volume density related to unloading. Sost mRNA expression in the cancellous metaphyseal bone was downregulated almost 2-fold, both 3 days and 10 days after unloading (P <0.05). A similar tendency was seen in the metaphyseal cortical bone, in which Sost was 1.5-fold downregulated (P <0.05) after 10days, but not significantly changed after 3days. In contrast, diaphyseal cortical Sost expression was instead upregulated 1.4-fold (P <0.05) following 3-day unloading, while there was no significant change after 10days. Cancellous bone volume density was 58% lower (P <0.001, compared to cage controls) in the unloaded limb but not significantly affected in the loaded limb. The results suggest that Sost mRNA expression in metaphyseal bone responds to mechanical unloading in an opposite direction to that observed in diaphyseal cortical bone. This proposes a more complex expression pattern for Sost in response to unloading. Therapeutics that target Sclerostin during altered loading conditions may result in local bone mass changes that are difficult to predict. [Copyright &y& Elsevier]

Bone mineral density (BMD) is a measure of a person's skeletal mineral content, and assessing BMD by dual x-ray absorptiometry (DEXA) can help to diagnose diseases of low bone density. In this study, we determine the heritability of BMD in male and female monozygotic twin subjects using DEXA in 13 specific anatomical regions. In an attempt to quantify the genetic contribution of gender and skeletal region to BMD heritability, we scanned 14 pairs of identical twins using DEXA and calculated the broad-sense heritability coefficient (H2) in each of the 13 different body regions. The region of the body that was most heritable for both genders was the head (H2 ≥ 95%). When males were compared to females, H2 values for male hip (H2 = 87%) and lower extremities (H2 = 90%) were higher than those in females (H2 = 49% and 56%, respectively). Conversely, H2 value for the female pelvis (H2 = 68%) was higher than that for males (H2 = 26%). These data show that different regions of the skeleton exhibit different degrees of heritability, and that the variation depends on gender. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:150-154, 2009 [ABSTRACT FROM AUTHOR]

Negative pressure wound therapy has become ubiquitous in orthopedic surgery and it is therefore important to understand the physiologic conditions of this therapy. The purpose of this study was to determine the magnitude and depth of negative pressure transmission into underlying muscle tissue in a wound model. We hypothesized that the negative pressure is not transmitted beyond 2 mm into underlying muscle tissue. Using both an isolated muscle and a live animal wound model, we applied open cell foam dressing to the tissue. Using a series of vacuum-assisted closure negative pressure settings (0, −75, −125, −200 mmHg) interstitial fluid pressure was measured in the underlying tissue with a solid-state pressure transducer catheter at 1/10 mm depth intervals. In the ex vivo isolated-muscle model, the effect of negative pressure wound therapy on interstitial fluid pressure was extinguished and not significantly different than controls at a depth <2 mm. In the live animal wound model, the magnitude of interstitial fluid pressures corresponded directly with negative pressure settings ( p<0.01) and inversely with depth into muscle ( p<0.01). Interstitial fluid pressures were significantly ( p<0.05) less than control interstitial fluid pressures (0 mmHg setting) at depths of 0.5, 0.4, and 0.9 mm below the foam/muscle interface when the applied pressures were −75, −125, and −200 mmHg, respectively. Negative pressure wound therapy penetrates no more than 1 mm into rabbit wound tissue at the highest negative pressure setting (−200 mmHg) when using open-cell foam dressing. [ABSTRACT FROM AUTHOR]

Microgravity in spaceflight produces headward fluid shifts which probably contribute to Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Developing new methods to mitigate these shifts is crucial for preventing SANS. One possible strategy is the use of self-generated lower body negative pressure (LBNP). This study evaluates biological or physiological effects induced by bed rest to simulate adaptations to microgravity. Participants were tested during powered LBNP and dynamic self-generated (SELF) LBNP at 25 mmHg for 15 min. The results were compared to the physiologic responses observed in seated upright and supine positions without LBNP, which served as controls for normal gravitational effects on fluid dynamics. Eleven participants' (five male, six female) heart rates, blood pressures, and cross-sectional areas (CSA) of left and right internal jugular veins (IJV) were monitored. Self-generated LBNP, which requires mild to moderate physical activity, significantly elevated heart rate and blood pressure (p < 0.01). Self-generated LBNP also significantly reduced right IJV CSA compared to supine position (p = 0.005), though changes on the left side were not significant (p = 0.365). While the effects of SELF and traditional LBNP on IJV CSA were largely similar, traditional LBNP significantly reduced IJV CSA on both sides. Given its low mass, volume, and power requirements, SELF LBNP is a promising countermeasure against SANS. Results from this study warrant longer-term studies of SELF LBNP under simulated spaceflight conditions. [ABSTRACT FROM AUTHOR]

The Artificial Gravity Bed Rest with European Space Agency (AGBRESA) study involved 2 campaigns of 60-day bed rest at 6° head down tilt in the:envihab facility in Cologne, Germany, in 2019. The objective was to determine whether centrifugation of supine subjects mitigates physiological changes that occur due to the exposure to the spaceflight analog of 6° head down tilt. A set of international standard measures was used to evaluate bone, muscle, nutritional status, ocular changes, and psychological state and to assess cardiovascular, sensorimotor, and immune systems functions. After 60 days of bed rest, the subjects who were not exposed to centrifugation had significant decreases in mineral density at the hip and lumbar spine, decreased muscle strength of the knee and ankle, reduced maximal aerobic capacity, orthostatic intolerance, and impaired balance and locomotion, as well as significant biochemical, immunological, and psychological alterations. A daily 30-min exposure to 1 Gz supine centrifugation at the center of mass (0.3 Gz at the head, 2 Gz at the feet) mitigated mineral density loss in the femur neck and lumbar spine; and lessened the effects of bed rest on aerobic capacity, biochemistry, and immunology. However, low statistical power could contribute to the non-significant effects that are reported. • 60-day bed rest induces decreased bone loss, muscle strength and aerobic capacity. • Bed rest also affects vascular, balance, immune, ocular, and psychology functions. • Daily 30-min of centrifugation mitigates biochemical and immunological alterations. • Centrifugation also mitigates bone loss and decreased aerobic capacity. [ABSTRACT FROM AUTHOR]

Abstract: Heavy backpacks are often used in extreme environments, for example by military during combat, therefore completion of tasks quickly and efficiently is of operational relevance. The purpose of this study was to quantify hemodynamic parameters (brachial artery Doppler and microvascular flow by photoplethysmography; tissue oxygenation by near-infrared spectroscopy; arterial oxygen saturation by pulse oximeter) and sensation in upper extremities and hands (Semmes-Weinstein monofilament test and 2-point discrimination test) while wearing a loaded backpack (12 kg) in healthy adults for 10 min. All values were compared to baseline before wearing a backpack. Moderate weight loaded backpack loads significantly decreased upper extremity sensation as well as all macrovascular and microvascular hemodynamic values. Decreased macrovascular and microvascular hemodynamics may produce neurological dysfunction and consequently, probably affect fine motor control of the hands. [Copyright &y& Elsevier]

PURPOSE: The purpose of this study was to investigate whether partial weight-bearing activity, at either one-sixth or one-third of body mass, blunts the deleterious effects of simulated microgravity (0G) after 21 d on muscle mass and quantitative/qualitative measures of bone. METHODS: Using a novel, previously validated partial weight-bearing suspension device, mice were subjected to 16% (G/3, i.e., simulated lunar gravity) or 33% (G/6, i.e., simulated Martian gravity) weight bearing for 21 d. One gravity control (1G, i.e., Earth gravity) and tail-suspended mice (0G, i.e., simulated microgravity) served as controls to compare the effects of simulated lunar and Martian gravity to both Earth and microgravity. RESULTS: Simulated microgravity (0G) resulted in an 8% reduction in body mass and a 28% lower total plantarflexor muscle mass (for both, P < 0.01) as compared with 1G controls, but one-sixth and one-third partial weight-bearing activity attenuated losses. Relative to 1G controls, trabecular bone volume fraction (-9% to -13%) and trabecular thickness (-10% to -14%) were significantly lower in all groups (P < 0.01). In addition, cancellous and cortical bone formation rates (BFR) were lower in all reduced weight-bearing groups compared with 1G controls (-46% to -57%, trabecular BFR; -73% to -85%, cortical BFR; P < 0.001). Animals experiencing one-third but not one-sixth weight bearing exhibited attenuated deficits in femoral neck mechanical strength associated with 0G. CONCLUSION: These results suggest that partial weight bearing (up to 33% of body mass) is not sufficient to protect against bone loss observed with simulated 0 g but does mitigate reductions in soleus mass in skeletally mature female mice. [ABSTRACT FROM AUTHOR]

Cardiovascular deconditioning after long duration spaceflight is especially challenging in women who have a lower orthostatic tolerance (OT) compared with men. We hypothesized that an exercise prescription, combining supine aerobic treadmill exercise in a lower body negative pressure (LBNP) chamber followed by 10 min of resting LBNP, three to four times a week, and flywheel resistive training every third day would maintain orthostatic tolerance (OT) in women during a 60-day head-down-tilt bed rest (HDBR). Sixteen women were assigned to two groups (exercise, control). Pre and post HDBR OT was assessed with a tilt/LBNP test until presyncope. OT time (mean +/- SE) decreased from 17.5 +/- 1.0 min to 9.1 +/- 1.5 min (-50 +/- 6%) in control group (P < 0.001) and from 19.3 +/- 1.3 min to 13.0 +/- 1.9 min (-35 +/- 7%) in exercise group (P < 0.001), with no significant difference in OT time between the two groups after HDBR (P = 0.13). Nevertheless, compared with controls post HDBR, exercisers had a lower heart rate during supine rest (mean +/- SE, 71 +/- 3 vs. 85 +/- 4, P < 0.01), a slower increase in heart rate and a slower decrease in stroke volume over the course of tilt/LBNP test (P < 0.05). Blood volume (mean +/- SE) decreased in controls (-9 +/- 2%, P < 0.01) but was maintained in exercisers (-4 +/- 3%, P = 0.17).Our results suggest that the combined exercise countermeasure did not significantly improve OT but protected blood volume and cardiovascular response to sub tolerance levels of orthostatic stress. [ABSTRACT FROM AUTHOR]

Spaceflight associated neuro‐ocular syndrome (SANS) is hypothesized to develop as a consequence of the chronic headward fluid shift that occurs in sustained weightlessness. We exposed healthy subjects (n = 24) to strict 6° head‐down tilt bed rest (HDTBR), an analog of weightlessness that generates a sustained headward fluid shift, and we monitored for ocular changes similar to findings that develop in SANS. Two‐thirds of the subjects received a daily 30‐min exposure to artificial gravity (AG, 1 g at center of mass, ~0.3 g at eye level) during HDTBR by either continuous (cAG, n = 8) or intermittent (iAG, n = 8) short‐arm centrifugation to investigate whether this intervention would attenuate headward fluid shift‐induced ocular changes. Optical coherence tomography images were acquired to quantify changes in peripapillary total retinal thickness (TRT), retinal nerve fiber layer thickness, and choroidal thickness, and to detect chorioretinal folds. Intraocular pressure (IOP), optical biometry, and standard automated perimetry data were collected. TRT increased by 35.9 µm (95% CI, 19.9–51.9 µm, p < 0.0001), 36.5 µm (95% CI, 4.7–68.2 µm, p = 0.01), and 27.6 µm (95% CI, 8.8–46.3 µm, p = 0.0005) at HDTBR day 58 in the control, cAG, and iAG groups, respectively. Chorioretinal folds developed in six subjects across the groups, despite small increases in IOP. Visual function outcomes did not change. These findings validate strict HDTBR without elevated ambient CO2 as a model for investigating SANS and suggest that a fluid shift reversal of longer duration and/or greater magnitude at the eye may be required to prevent or mitigate SANS. [ABSTRACT FROM AUTHOR]

Key points: Carbon dioxide levels are mildly elevated on the International Space Station and it is unknown whether this chronic exposure causes physiological changes to astronauts.We combined ∼4 mmHg ambient PCO2 with the strict head‐down tilt bed rest model of spaceflight and this led to the development of optic disc oedema in one‐half of the subjects.We demonstrate no change in arterialized PCO2, cerebrovascular reactivity to CO2 or the hypercapnic ventilatory response.Our data suggest that the mild hypercapnic environment does not contribute to the development of spaceflight associated neuro‐ocular syndrome. Chronically elevated carbon dioxide (CO2) levels can occur in confined spaces such as the International Space Station. Using the spaceflight analogue 30 days of strict 6° head‐down tilt bed rest (HDTBR) in a mild hypercapnic environment (PCO2 = ∼4 mmHg), we investigated arterialized PCO2, cerebrovascular reactivity and the hypercapnic ventilatory response in 11 healthy subjects (five females) before, on days 1, 9, 15 and 30 of bed rest (BR), and 6 and 13 days after HDTBR. During all HDTBR time points, arterialized PCO2 was not significantly different from the pre‐HDTBR measured in the 6° HDT posture, with a mean (95% confidence interval) increase of 1.2 mmHg (–0.2 to 2.5 mmHg, P = 0.122) on day 30 of HDTBR. Respiratory acidosis was never detected, although a mild metabolic alkalosis developed on day 30 of HDTBR by a mean (95% confidence interval) pH change of 0.032 (0.022–0.043; P < 0.001), which remained elevated by 0.021 (0.011–0.031; P < 0.001) 6 days after HDTBR. Arterialized pH returned to pre‐HDTBR levels 13 days after BR with a change of –0.001 (–0.009 to 0.007; P = 0.991). Compared to pre‐HDTBR, cerebrovascular reactivity during and after HDTBR did not change. Baseline ventilation, ventilatory recruitment threshold and the slope of the ventilatory response were similar between pre‐HDTBR and all other time points. Taken together, these data suggest that the mildly increased ambient PCO2 combined with 30 days of strict 6° HDTBR did not change arterialized PCO2 levels. Therefore, the experimental conditions were not sufficient to elicit a detectable physiological response. Key points: Carbon dioxide levels are mildly elevated on the International Space Station and it is unknown whether this chronic exposure causes physiological changes to astronauts.We combined ∼4 mmHg ambient PCO2 with the strict head‐down tilt bed rest model of spaceflight and this led to the development of optic disc oedema in one‐half of the subjects.We demonstrate no change in arterialized PCO2, cerebrovascular reactivity to CO2 or the hypercapnic ventilatory response.Our data suggest that the mild hypercapnic environment does not contribute to the development of spaceflight associated neuro‐ocular syndrome. [ABSTRACT FROM AUTHOR]

Background: The current gold standard for diagnosing acute compartment syndrome (ACS) is an assessment of clinical signs, invasive measurement of intramuscular pressure (IMP), and measurement of local perfusion pressure. However, IMP measurements have several shortcomings, including pain, risk of infection, risk of technique error, plugging of the catheter tip, lack of consensus on the diagnostic pressure threshold, and lack of specificity and sensitivity. The objective of this study was to evaluate muscle hemodynamics, oxygenation, and pH as diagnostic parameters in a human model of ACS. We hypothesized that as IMP increases, muscle microvascular blood flow, oxygenation, and pH decrease in the anterior compartment of a leg at heart level and that they decrease significantly more when the leg is elevated further.Methods: An external pneumatic leg pressure chamber, combined with a venous stasis thigh cuff, was used to increase IMP and simulate ACS. Eight healthy subjects (5 males and 3 females; mean age, 26 years) had photoplethysmography and near-infrared spectroscopy-pH sensors placed over the middle aspect of the tibialis anterior muscle of the right (experimental) and left (control) legs. Leg chamber pressure conditions (40, 50, and 60 mm Hg) were applied in a randomized order after baseline measurements were taken. Data were collected continuously for each 11-minute pressure condition, with an 11-minute recovery period after each condition, and the average of the last 6 minutes was used for data analyses. The same protocol was repeated with each subject's legs elevated 12 cm above heart level. Data were analyzed using repeated-measures analysis of variance (ANOVA).Results: As IMP increased, muscle microvascular blood flow (p = 0.01), oxygenation (p < 0.001), and pH (p < 0.001) all decreased significantly in the experimental leg compared with the control leg. At all IMP levels, leg elevation significantly decreased muscle oxygenation (p = 0.013) and perfusion pressure (p = 0.03) compared with the control leg at heart level.Conclusions: These results indicate that muscle microvascular blood flow, oxygenation, pH, and perfusion pressure decrease significantly as IMP increases in a human model of ACS.Clinical Relevance: This study identifies hemodynamic and metabolic parameters as potential noninvasive diagnostic tools for ACS. [ABSTRACT FROM AUTHOR]

Study Design: Prospective case series.Objective: Evaluate lumbar paraspinal muscle (PSM) cross-sectional area and intervertebral disc (IVD) height changes induced by a 6-month space mission on the International Space Station. The long-term objective of this project is to promote spine health and prevent spinal injury during space missions and here on Earth.Summary Of Background Data: National Aeronautics and Space Administration (NASA) crewmembers have a 4.3 times higher risk of herniated IVDs, compared with the general and military aviator populations. The highest risk occurs during the first year after a mission. Microgravity exposure during long-duration spaceflights results in approximately 5 cm lengthening of body height, spinal pain, and skeletal deconditioning. How the PSMs and IVDs respond during spaceflight is not well described.Methods: Six NASA crewmembers were imaged supine with a 3 Tesla magnetic resonance imaging. Imaging was conducted preflight, immediately postflight, and then 33 to 67 days after landing. Functional cross-sectional area (FCSA) measurements of the PSMs were performed at the L3-4 level. FCSA was measured by grayscale thresholding within the posterior lumbar extensors to isolate lean muscle on T2-weighted scans. IVD heights were measured at the anterior, middle, and posterior sections of all lumbar levels. Repeated measures analysis of variance was used to determine significance at P < 0.05, followed by post-hoc testing.Results: Paraspinal lean muscle mass, as indicated by the FCSA, decreased from 86% of the total PSM cross-sectional area down to 72%, immediately after the mission. Recovery of 68% of the postflight loss occurred during the next 6 weeks, still leaving a significantly lower lean muscle fractional content compared with preflight values. In contrast, lumbar IVD heights were not appreciably different at any time point.Conclusion: The data reveal lumbar spine PSM atrophy after long-duration spaceflight. Some FCSA recovery was seen with 46 days postflight in a terrestrial environment, but it remained incomplete compared with preflight levels.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Leg muscle mass and strength are decreased during reduced activity and nonweight-bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill exercise within lower body negative pressure (LBNPEX) provides full-body weight loading during BR and may prevent muscle deconditioning. We hypothesized that a 40-min interval exercise protocol performed against LBNPEX 6 days week -1 would attenuate losses in leg lean mass (LLM), strength, and endurance during 6° head-down tilt BR, with similar benefits for men and women. Fifteen pairs of healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with one sibling of each twin pair assigned randomly as the non-exercise control (CON) and the other twin as the exercise subject (EX). Before and after BR, LLM and isokinetic leg strength and endurance were measured. Mean knee and ankle extensor and flexor strength and endurance and LLM decreased from pre- to post-BR in the male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle extensor strength, and LLM were maintained in the male EX subjects. In contrast, no pre- to post-BR changes were significant in the female subjects, either CON or EX, likely due to their lower pre-BR values. Importantly, the LBNPEX countermeasure prevents or attenuates declines in LLM as well as extensor leg strength and endurance. Individuals who are stronger, have higher levels of muscular endurance, and/or have greater LLM are likely to experience greater losses during BR than those who are less fit. [ABSTRACT FROM AUTHOR]

ABSTRACT Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure. Caudal motion segments from six mice returned from a 30-day Bion M1 mission and eight vivarium controls were loaded to failure in four-point bending. After testing, specimens were processed using histology to determine the location of failure, and adjacent motion segments were scanned with micro-computed tomography (μCT) to quantify bone properties. We observed that spaceflight significantly shortened the nonlinear toe region of the force-displacement curve by 32% and reduced the bending strength by 17%. Flight mouse spinal segments tended to fail within the growth plate and epiphyseal bone, while controls tended to fail at the disc-vertebra junction. Spaceflight significantly reduced vertebral bone volume fraction, bone mineral density, and trabecular thickness, which may explain the tendency of flight specimens to fail within the epiphyseal bone. Together, these results indicate that vertebral bone loss during spaceflight may degrade spine bending properties and contribute to increased disc herniation risk in astronauts. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:48-57, 2016. [ABSTRACT FROM AUTHOR]

The purpose of this study was to directly assess sex differences in bone loss, bone biochemistry, and renal stone risk in bed rest. Bed rest simulates some spaceflight effects on human physiology and can be used to address the potential existence of sex-specific effects on bone metabolism and renal stone risk in space. We combined data from the control subjects in five head-down-tilt bed rest studies (combined n = 50 men, 24 women) of differing durations (14-90 days). All subjects were healthy volunteers. Mean age was 35 ± 9 years for women and 33 ± 8 years for men. The main outcome measures were bone density and biochemistry, and renal stone risk chemistry. Before bed rest began, men had higher bone mineral density and content ( P < 0.001), and excreted more biomarkers of bone resorption and calcium per day than did women ( P < 0.05). These differences remained during bed rest. A number of urine chemistry analytes increased (e.g., calcium) or decreased (e.g., sodium, citrate, and urine volume) significantly for men and women during bed rest. These changes may predispose men to higher stone risk. Men and women do not have substantially different responses to the skeletal unloading of bed rest. [ABSTRACT FROM AUTHOR]

Nilsson MI, Greene NP, Dobson JP, Wiggs MP, Gasier HG, Macias BR, Shimkus KL, Fluckey JD. Insulin resistance syndrome blunts the mitochondrial anabolic response following resistance exercise. Am J Physiol Endocrinol Metab 299: E466-E474, 2010. First published July 6, 2010; doi:10.1152/ajpendo.00118.2010.--Metabolic risk factors associated with insulin resistance syndrome may attenuate augmentations in skeletal muscle protein anabolism following contractile activity. The purpose of this study was to investigate whether or not the anabolic response, as defined by an increase in cumulative fractional protein synthesis rates (24-h FSR) following resistance exercise (RE), is blunted in skeletal muscle of a well-established rodent model of insulin resistance syndrome. Four-month-old lean (Fa/?) and obese (fa/fa) Zucker rats engaged in four lower body RE sessions over 8 days, with the last bout occurring 16 h prior muscle harvest. A priming dose of deuterium oxide (²H2O) and ²H2O-enriched drinking water were administered 24 h prior to euthanization for assessment of cumulative FSR. Fractional synthesis rates of mixed (-5%), mitochondrial (-1%), and cytosolic (+15%), not myofibrillar, proteins (- 16%, P = 0.012) were normal or elevated in gastrocnemius muscle of unexercised obese rats. No statistical differences were found in the anabolic response of cytosolic and myofibrillar subfractions between phenotypes, but obese rats were not able to augment 24-h FSR of mitochondria to the same extent as lean rats following RE (+14% vs. +28%, respectively). We conclude that the mature obese Zucker rat exhibits a mild, myofibrillar-specific suppression in basal FSR and a blunted mitochondrial response to contractile activity in mixed gastrocnemius muscle. These findings underscore the importance of assessing synthesis rates of specific myocellular subfractions to fully elucidate perturbations in basal protein turnover rates and differential adaptations to exercise stimuli metabolic disease. [ABSTRACT FROM AUTHOR]

Abstract: Bone loss associated with disuse during bed rest (BR), an analog of space flight, can be attenuated by exercise. In previous studies, the efficacy of either aerobic or resistive exercise countermeasures has been examined separately. We hypothesized that a regimen of combined resistive and aerobic exercise during BR would prevent bone resorption and promote bone formation. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6° head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n =8) performed no countermeasure. Exercise subjects (EX, n =8) participated in an exercise program during BR, alternating between supine treadmill exercise within lower body negative pressure (3–4 d wk−1) and flywheel resistive exercise (2–3 d wk−1). By the last week of BR, excretion of helical peptide (CON, 79%±44 increase; EX, 64%±50, mean±SD) and N-terminal cross-linking telopeptide (CON, 51%±34; EX, 43%±56), markers of bone resorption, were greater than they were before BR in both groups (P <0.05). However, serum concentrations of the bone formation marker procollagen type I N propeptide were greater in EX than CON throughout and after bed rest (P <0.05), while concentrations of the bone formation marker bone alkaline phosphatase tended to be greater in EX than CON. Dual-energy X-ray absorptiometry results indicated that the exercise treatment significantly (P <0.05) attenuated loss of hip and leg bone mineral density in EX compared to CON. The combination of resistive and aerobic exercise did not prevent bone resorption but did promote bone formation, and helped mitigate the net bone loss associated with simulated microgravity. [Copyright &y& Elsevier]

Background: Acute compartment syndrome has been an underreported complication during spine surgery with the patient positioned on the so-called 90/90 kneeling frame (with 90 degrees of both hip and knee flexion), presumably because of elevated intramuscular pressures in the dependent leg compartments. The purpose of the present study was to characterize and quantify certain parameters that affect the risk for acute compartment syndrome experimentally and to make objective comparisons with other spine surgery positions.Methods: Eight healthy volunteers were positioned in three spine surgery positions: the 90/90 kneeling position, the so-called 45/45 suspended position (with the hips and knees both flexed to 45 degrees with the legs suspended on a sling), and the prone position. Intramuscular pressures were measured in all four left leg compartments with slit catheters. Local blood pressure and applied load beneath the leg were also measured.Results: The 90/90 kneeling position was associated with significantly increased intramuscular pressure in the anterior compartment (30.8 +/- 5.7 mm Hg) in comparison with the prone position (13.5 +/- 1.7 mm Hg) and the 45/45 suspended position (13.8 +/- 1.7 mm Hg). In the 90/90 kneeling position, these values correlated with subject weight (r = 0.72, p = 0.045) and the applied body weight load measured beneath the leg (r = 0.74, p = 0.037). The mean differences between intramuscular pressure and ankle blood pressure were more pronounced as the position of the ankle dropped below the level of the heart in the 45/45 suspended and the 90/90 kneeling positions.Conclusions: The 90/90 kneeling position results in elevated intramuscular pressure in the anterior compartment of the leg. This elevated pressure correlates also with subject weight. The 90/90 kneeling position may predispose patients to the development of an acute compartment syndrome during prolonged spine surgery, with heavier patients being at increased risk. In certain instances, the surgeon may consider using the 45/45 suspended position to minimize this risk. [ABSTRACT FROM AUTHOR]

Background: Acute compartment syndrome has been an underreported complication during spine surgery with the patient positioned on the so-called 90/90 kneeling frame (with 900 of both hip and knee flexion), presumably because of elevated intramuscular pressures in the dependent leg compartments. The purpose of the present study was to characterize and quantify certain parameters that affect the risk for acute compartment syndrome experimentally and to make objective comparisons with other spine surgery positions. Methods: Eight healthy volunteers were positioned in three spine surgery positions: the 90/90 kneeling position, the so-called 45/45 suspended position (with the hips and knees both flexed to 45° with the legs suspended on a sling), and the prone position. Intramuscular pressures were measured in all four left leg compartments with slit catheters. Local blood pressure and applied load beneath the leg were also measured. Results: The 90/90 kneeling position was associated with significantly increased intramuscular pressure in the anterior compartment (30.8 ± 5.7 mm Hg) in comparison with the prone position (13.5 ± 1.7 mm Hg) and the 45/45 suspended position (13.8 ± 1.7 mm Hg). In the 90/90 kneeling position, these values correlated with subject weight (r = 0.72, p = 0.045) and the applied body weight load measured beneath the leg (r = 0.74, p = 0.037). The mean differences between intramuscular pressure and ankle blood pressure were more pronounced as the position of the ankle dropped below the level of the heart in the 45/45 suspended and the 90/90 kneeling positions. Conclusions: The 90/90 kneeling position results in elevated intramuscular pressure in the anterior compartment of the leg. This elevated pressure correlates also with subject weight. The 90/90 kneeling position may predispose patients to the development of an acute compartment syndrome during prolonged spine surgery, with heavier patients being at increased risk. In certain instances, the surgeon may consider using the 45/45 suspended position to minimize this risk. [ABSTRACT FROM AUTHOR]

The article discusses whether lower-body negative pressure (LBNPex) would protect against loss of upright exercise (VO2peak) and sprint performance during a 30-day bed rest. Participants were divided into a control group (CON) who do not perform exercise, and the other was assigned to an exercise group (EX) wherein they performed an upright graded exercise test to volitional fatigue and sprint test, during and after bed rest. The results indicated that the VO2peak was decreased and sprint time was increased in the CON participants but was maintained in the EX participants. Researchers concluded that exercise countermeasure protocol may help in the prevention of microgravity-induced deconditioning during space flight.

Abstract: Supine weight-bearing exercise within lower body negative pressure (LBNP) alleviates some of the skeletal deconditioning induced by simulated weightlessness in men. We examined this potential beneficial effect in women. Because dietary acid load affected the degree of bone resorption in men during bed rest, we also investigated this variable in women. Subjects were 7 pairs of female identical twins assigned at random to 2 groups, sedentary bed rest (control) or bed rest with supine treadmill exercise within LBNP. Dietary intake was controlled and monitored. Urinary calcium and markers of bone resorption were measured before bed rest and on bed rest days 5/6, 12/13, 19/20, and 26/27. Bone mineral content was assessed by dual-energy X-ray absorptiometry before and after bed rest. Data were analyzed by repeated-measures two-way analysis of variance. Pearson correlation coefficients were used to define the relationships between diet and markers of bone metabolism and to estimate heritability of markers. During bed rest, all markers of bone resorption and urinary calcium and phosphorus increased (P <0.001); parathyroid hormone (P =0.06), bone-specific alkaline phosphatase (P =0.06), and 1,25-dihydroxyvitamin D (P =0.09) tended to decrease. LBNP exercise tended to mitigate bone density loss. The ratio of dietary animal protein to potassium was positively correlated with urinary calcium excretion for all weeks of bed rest in the control group, but only during weeks 1 and 3 in the exercise group. Pre-bed rest data suggested that many markers of bone metabolism have strong genetic determinants. Treadmill exercise within LBNP had less of a protective effect on bone resorption during bed rest in women than previously published results had shown for its effect in men, but the same trends were observed for both sexes. Dietary acid load of these female subjects was significantly correlated with calcium excretion but not with other bone resorption markers. [Copyright &y& Elsevier]