Neuro-ophthalmological changes in healthy females exposed to a 5-day dry immersion: a pilot study.

After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called "spaceflight associated neuro-ocular syndrome" (SANS). The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spaceflight on SANS in women due to the fact that fewer female astronauts have spent time in long-term missions. The objective is to determine whether similar ophthalmological changes occur in healthy women after short-term exposure to microgravity. The auto-refractometer was used to determine objective refraction. The best corrected distance visual acuity was assessed with a Monoyer chart. The ocular axial length was assessed using optical biometry. The applanation tonometry was used to determine intraocular pressure. Peripapillary retinal nerve fibre layer thickness (pRNFLT), macular total retinal thickness, and ganglion cell complex (GCC) were measured using optical coherence tomography. Ocular axial length is reduced after DI. pRNFL is thickest after DI specifically in the temporal, temporal-inferior, and nasal-inferior quadrants. Macular total retinal at the inferior quadrant of the 6-mm ring is thickest after DI. Global GCC is thinnest after DI. In this study, 5 days of DI induces slight but significant ophthalmological changes in women. However, these subtle changes do not correspond to criteria defined in SANS.

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.

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.

A dry immersion model of microgravity modulates platelet phenotype, miRNA signature, and circulating plasma protein biomarker profile.

Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.

Does Physical Inactivity Induce Significant Changes in Human Gut Microbiota? New Answers Using the Dry Immersion Hypoactivity Model.

Gut microbiota, a major contributor to human health, is influenced by physical activity and diet, and displays a functional cross-talk with skeletal muscle. Conversely, few data are available on the impact of hypoactivity, although sedentary lifestyles are widespread and associated with negative health and socio-economic impacts. The study aim was to determine the effect of Dry Immersion (DI), a severe hypoactivity model, on the human gut microbiota composition. Stool samples were collected from 14 healthy men before and after 5 days of DI to determine the gut microbiota taxonomic profiles by 16S metagenomic sequencing in strictly controlled dietary conditions. The α and ß diversities indices were unchanged. However, the operational taxonomic units associated with the Clostridiales order and the Lachnospiraceae family, belonging to the Firmicutes phylum, were significantly increased after DI. Propionate, a short-chain fatty acid metabolized by skeletal muscle, was significantly reduced in post-DI stool samples. The finding that intestine bacteria are sensitive to hypoactivity raises questions about their impact and role in chronic sedentary lifestyles.

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.

Effects of Resistance Exercise with or without Whey Protein Supplementation on Ocular Changes after a 21-Day Head-Down Bed Rest.

Neuro-ophthalmological changes have been reported after prolonged exposure to microgravity; however, the pathophysiology remains unclear. The objectives of the present study were twofold: (1) to assess the neuro-ophthalmological impact of 21 days of head-down bed rest (HDBR) and (2) to determine the effects of resistance vibration exercise (RVE) alone or combined with nutritional supplementation (NeX). In this case, 12 healthy male subjects completed three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Intraocular pressure (IOP) was assessed by applanation tonometry. Retinal nerve fiber layer thickness (RNFLT) was assessed with spectral-domain optical coherence tomography, before HDBR and between Day 2 and Day 4 after each session of HDBR. In CON condition, IOP was preserved; while in RVE and NeX conditions, IOP was increased. In CON condition, RNFLT was preserved after HDBR. RVE and NeX conditions did not have significant effects on RNFLT. This study showed that a 3-week HDBR did not induce significant ophthalmological changes. However, RVE induced an elevation in IOP after HDBR. Nutritional supplementation did not reduce or exacerbate the side effects of RVE.

Simulated microgravity disturbs iron metabolism and distribution in humans: Lessons from dry immersion, an innovative ground-based human model.

The objective of the present study was to determine the effects of dry immersion, an innovative ground-based human model of simulated microgravity and extreme physical inactivity, on iron homeostasis and distribution. Twenty young healthy men were recruited and submitted to 5 days of dry immersion (DI). Fasting blood samples and MRI were performed before and after DI exposure to assess iron status, as well as hematological responses. DI increased spleen iron concentrations (SIC), whereas hepatic iron store (HIC) was not affected. Spleen iron sequestration could be due to the concomitant increase in serum hepcidin levels (P < .001). Increased serum unconjugated bilirubin, as well as the rise of serum myoglobin levels support that DI may promote hemolysis and myolysis. These phenomena could contribute to the concomitant increase of serum iron and transferrin saturation levels (P < .001). As HIC remained unchanged, increased serum hepcidin levels could be due both to higher transferrin saturation level, and to low-grade pro-inflammatory as suggested by the significant rise of serum ferritin and haptoglobin levels after DI (P = .003 and P = .003, respectively). These observations highlight the need for better assessment of iron metabolism in bedridden patients, and an optimization of the diet currently proposed to astronauts.

DI-5-CUFFS: Venoconstrictive Thigh Cuffs Limit Body Fluid Changes but Not Orthostatic Intolerance Induced by a 5-Day Dry Immersion.

Venoconstrictive thigh cuffs are used by cosmonauts to ameliorate symptoms associated with cephalad fluid shift. A ground simulation of microgravity, using the dry immersion (DI) model, was performed to assess the effects of thigh cuffs on body fluid changes and dynamics, as well as on cardiovascular deconditioning. Eighteen healthy men (25-43 years), randomly divided into two groups, (1) control group or (2) group with thigh cuffs worn 10 h/day, underwent 5-day DI. Cardiovascular responses to orthostatic challenge were evaluated using the lower body negative pressure (LBNP) test; body fluid changes were assessed by bio-impedance and hormonal assay; plasma volume evolution was estimated using hemoglobin-hematocrit; subjective tolerance was assessed by questionnaires. DI induced a decrease in plasma volume of 15-20%. Reduction in total body water of 3-6% stabilized toward the third day of DI. This reduction was derived mostly from the extracellular compartment. During the acute phase of DI, thigh cuffs limited the decrease in renin and the increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), the loss in total body water, and tended to limit the loss in calf volume, extracellular volume and plasma volume. At the later stable phase of DI, a moderate protective effect of thigh cuffs remained evident on the body fluids. Orthostatic tolerance time dropped after DI without significant difference between groups. Thigh cuff countermeasure slowed down and limited the loss of body water and tended to limit plasma loss induced by DI. These observed physiological responses persisted during periods when thigh cuffs were removed. However, thigh cuffs did not counteract decreased tolerance to orthostatic challenge.

An Alzheimer Disease Challenge Model: 24-Hour Sleep Deprivation in Healthy Volunteers, Impact on Working Memory, and Reversal Effect of Pharmacological Intervention: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

PURPOSE/BACKGROUND: Alzheimer disease (AD) is a public health issue because of the low number of symptomatic drugs and the difficulty to diagnose it at the prodromal stage. The need to develop new treatments and to validate sensitive tests for early diagnosis could be met by developing a challenge model reproducing cognitive impairments of AD. Therefore, we implemented a 24-hour sleep deprivation (SD) design on healthy volunteers in a randomized, double-blind, placebo-controlled, crossover study on 36 healthy volunteers. METHODS/PROCEDURE: To validate the SD model, cognitive tests were chosen to assess a transient worsening of cognitive functions after SD and a restoration under modafinil as positive control (one dose of 200 mg). Then, the same evaluations were replicated after 15 days of donepezil (5 mg/d) or memantine (10 mg/d). The working memory (WM) function was assessed by the N-back task and the rapid visual processing (RVP) task. FINDINGS/RESULTS: The accuracy of the N-back task and the reaction time of the RVP revealed the alteration of the WM with SD and its restoration with modafinil (changes in score after SD compared with baseline before SD), respectively, in the placebo group and in the modafinil group (-0.2% and +1.0% of satisfactory answers, P = 0.022; +21.3 and +1.9 milliseconds of reaction time, P = 0.025). Alzheimer disease drugs also tended to reverse this deterioration: the accuracy of the N-back task was more stable through SD (compared with -3.0% in the placebo group, respectively, in the memantine group and in the donepezil group: -1.4% and -1.6%, P = 0.027 and P = 0.092) and RVP reaction time was less impacted (compared with +41.3 milliseconds in the placebo group, respectively, in the memantine group and in the donepezil group: +16.1 and +29.3 milliseconds, P = 0.034 and P = 0.459). IMPLICATIONS/CONCLUSIONS: Our SD challenge model actually led to a worsening of WM that was moderated by both modafinil and AD drugs. To use this approach, the cognitive battery, the vulnerability of the subjects to SD, and the expected drug effect should be carefully considered.

Effects of short-term dry immersion on bone remodeling markers, insulin and adipokines.

BACKGROUND: Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones. METHODS: Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI24h, DI48H and DI72h), then after recovery (R+3h and R+24h). Markers of bone turnover, phosphocalcic metabolism, adipokines and associated factors were measured. RESULTS: Bone resorption as assessed by tartrate-resistant acid phosphatase isoform 5b and N-terminal crosslinked telopeptide of type I collagen levels increased as early as DI24h. At the same time, total procollagen type I N- and C-terminal propeptides and osteoprotegerin, representing bone formation markers, decreased. Total osteocalcin [OC] was unaffected, but its undercarboxylated form [Glu-OC] increased from DI24h to R+3h. The early and progressive increase in bone alkaline phosphatase activities suggested an increased mineralization. Dickkopf-1 and sclerostin, as negative regulators of the Wnt-ß catenin pathway, were unaltered. No change was observed either in phosphocalcic homeostasis (calcium and phosphate serum levels, 25-hydroxyvitamin D, fibroblast growth factor 23 [FGF23]) or in inflammatory response. Adiponectemia was unchanged, whereas circulating leptin concentrations increased. Neutrophil gelatinase-associated lipocalin [lipocalin-2], a potential regulator of bone homeostasis, was found elevated by 16% at R+3h compared to DI24h. The secretory form of nicotinamide phosphoribosyl-transferase [visfatin] concentrations almost doubled after one day of DI and remained elevated. Serum insulin-like growth factor 1 levels progressively increased. Fasting insulin concentrations increased during the entire DI, whereas fasting glucose levels tended to be higher only at DI24h and then returned to BDC values. Changes in bone resorption parameters negatively correlated with changes in bone formation parameters. Percent changes of ultra-sensitive C-reactive protein positively correlated with changes in osteopontin, lipocalin-2 and fasting glucose. Furthermore, a positive correlation was found between changes in FGF23 and Glu-OC, the two main osteoblast-/osteocyte-derived hormones. CONCLUSION: Our results demonstrated that DI induced an unbalanced remodeling activity and the onset of insulin resistance. This metabolic adaptation was concomitant with higher levels of Glu-OC. This finding confirms the role of bone as an endocrine organ in humans. Furthermore, visfatin for which a great responsiveness was observed could represent an early and sensitive marker of unloading in humans.

Early structural and functional signature of 3-day human skeletal muscle disuse using the dry immersion model.

KEY POINTS: Our study contributes to the characterization of muscle loss and weakness processes induced by a sedentary life style, chronic hypoactivity, clinical bed rest, immobilization and microgravity. This study, by bringing together integrated and cellular evaluation of muscle structure and function, identifies the early functional markers and biomarkers of muscle deconditioning. Three days of muscle disuse in healthy adult subjects is sufficient to significantly decrease muscle mass, tone and force, and to induce changes in function relating to a weakness in aerobic metabolism and muscle fibre denervation. The outcomes of this study should be considered in the development of an early muscle loss prevention programme and/or the development of pre-conditioning programmes required before clinical bed rest, immobilization and spaceflight travel. ABSTRACT: Microgravity and hypoactivity are associated with skeletal muscle deconditioning. The decrease of muscle mass follows an exponential decay, with major changes in the first days. The purpose of the study was to dissect out the effects of a short-term 3-day dry immersion (DI) on human quadriceps muscle function and structure. The DI model, by suppressing all support zones, accurately reproduces the effects of microgravity. Twelve healthy volunteers (32 ± 5 years) completed 3 days of DI. Muscle function was investigated through maximal voluntary contraction (MVC) tests and muscle viscoelasticity. Structural experiments were performed using MRI analysis and invasive experiments on muscle fibres. Our results indicated a significant 9.1% decrease of the normalized MVC constant (P = 0.048). Contraction and relaxation modelization kinetics reported modifications related to torque generation (kACT  = -29%; P = 0.014) and to the relaxation phase (kREL  = +34%; P = 0.040) after 3 days of DI. Muscle viscoelasticity was also altered. From day one, rectus femoris stiffness and tone decreased by, respectively, 7.3% (P = 0.002) and 10.2% (P = 0.002), and rectus femoris elasticity decreased by 31.5% (P = 0.004) after 3 days of DI. At the cellular level, 3 days of DI translated into a significant atrophy of type I muscle fibres (-10.6 ± 12.1%, P = 0.027) and an increased proportion of hybrid, type I/IIX fibre co-expression. Finally, we report an increase (6-fold; P = 0.002) in NCAM+ muscle fibres, showing an early denervation process. This study is the first to report experiments performed in Europe investigating human short-term DI-induced muscle adaptations, and contributes to deciphering the early changes and biomarkers of skeletal muscle deconditioning.

Effects of plantar stimulation on cardiovascular response to orthostatism.

PURPOSE: Walking is a complex locomotor process that involves both spinal cord reflexes and cortical integration of peripheral nerve input. Maintaining an upright body position requires not only neuromuscular activity but also cardiovascular regulation. We postulated that plantar mechanical stimulation might modulate autonomic nervous system activity and, thereby, impact blood pressure adaptation during standing. METHODS: Twelve healthy subjects underwent three randomly ordered 45-min 70°-saddle tilt tests while the plantar surfaces of the feet were stimulated using specially engineered Korvit boots in the following modes: (1) no stimulation, (2) disrupted stimulation, and (3) walking mode. Orthostatic tolerance time was measured for each trial. During testing, we obtained an electrocardiogram and measured blood pressure, skin blood flow, and popliteal vein cross-sectional area. We estimated central hemodynamics, baroreflex sensitivity and heart rate variability. RESULTS: Orthostatic tolerance time was not found to differ significantly between test conditions (37.2 ± 10.4, 40.9 ± 7.6, and 41.8 ± 8.2 min, for no stimulation, disrupted stimulation, and walking mode, respectively). No significant differences between treatment groups were observed for stroke volume or cardiac baroreflex sensitivity, both of which decreased significantly from baseline during tilt testing in all groups. Cardiac sympathetic index and popliteal vein cross-sectional area increased at the end of the tilt period in all groups, without significant differences between treatments. CONCLUSIONS: Plantar mechanical stimulation is insufficient for immediate modulation of cardiac sympathetic and parasympathetic activity under orthostatic stress.

Short-arm human centrifugation with 0.4g at eye and 0.75g at heart level provides similar cerebrovascular and cardiovascular responses to standing.

BACKGROUND AND PURPOSE: Orthostatic intolerance continues to be a problem with astronauts upon return to Earth as a result of cerebral and cardiovascular adaptations to weightlessness. We tested the hypothesis that artificial gravity from a short-arm human centrifuge (SAHC) could provide cerebral and cardiovascular stimuli similar to upright posture and thereby serve as a suitable countermeasure. METHODS: We compared cardiovascular and cerebrovascular responses before, during, and after exposure to hyper-G with that of standing in healthy young participants. The head was positioned such that the middle cerebral artery (MCA) was 0.46 m from the center of rotation. Two levels of hyper-G that provided 1g and 2g at foot level were investigated. Continuous blood pressure, heart rate, calf blood volume, MCA mean blood flow velocity (MFV) and end-tidal CO2 were measured. RESULTS: Blood pressure at the level of the MCA (BP-MCA) and MFV was reduced during stand and at 2g. The relationship between MFV and BP-MCA at 2g was different from supine and similar to standing, while 1g centrifugation was not different from supine. The cardiovascular system was also not different from supine at 1g but was similarly challenged in 2g compared to stand. CONCLUSIONS: Our data suggest that short-arm centrifugation 2g at the feet, with the head offset 0.5 m from the center, provides similar cardiovascular and cerebral responses to standing. This supports the hypothesis that passive 2g SAHC exposure at the feet could be used as a countermeasure for in-flight cardiovascular and cerebrovascular deconditioning.

Fitness, blood, and urine measurements from the 2009 European astronaut selection medical examination.

INTRODUCTION: The European Space Agency conducted an astronaut selection campaign in 2008-09 which attracted over 8000 applicants. Of those, 45 made the final assessment stage: the medical examination (MEX). This retrospective, observational study reports exercise and fitness data, lipid profiles and other results of interest from the blood and urine samples of this niche subpopulation. METHODS: All the applicants that reached the MEX completed a Bruce protocol test and a standard blood draw (12 h of fasting, water intake was ad libitum) was collected together with a 24-h urine collection. All the results were compared to either a comparative population or reference range. RESULTS: The applicants had comparable fitness levels to the 90th percentile of their age group. The lipid profiles were observed to be within the 'optimal' or 'desirable' ranges. Bilirubin and creatinine clearance were measured at 1.2 (+/- 0.40) mg x dl(-1) and 131.0 (+/- 25.81) ml x min(-1), respectively, and both were shown to be significantly higher than their respective normative ranges, while urinary creatinine (0.65 (+/- 0.19) g x L(-1)) was significantly lower than the reference range. DISCUSSION: Overall, the results from the Bruce protocol and lipid profile show that the final round applicants were in good health and physically active. The most likely cause of the elevated bilirubin and creatinine levels was 'last-minute' exercise conducted by the final round applicants before the MEX and the low levels of urinary creatinine may be attributed to drinking high quantities of water with an associated hypovolemia, diluting the urine.

Influence of age, circadian and homeostatic processes on inhibitory motor control: a Go/Nogo task study.

INTRODUCTION: The contribution of circadian system and sleep pressure influences on executive performance as a function of age has never been studied. The aim of our study was to determine the age-related evolution of inhibitory motor control (i.e., ability to suppress a prepotent motor response) and sustained attention under controlled high or low sleep pressure conditions. METHODS: 14 healthy young males (mean age = 23 ± 2.7; 20-29 years) and 11 healthy older males (mean age = 68 ± 1.4; 66-70 years) were recruited. The volunteers were placed for 40 hours in "constant routine". In the "Sleep Deprivation SD" condition, the volunteer was kept awake for 40 hours to obtain a high sleep pressure condition interacting with the circadian process. In the "NAP" condition, the volunteer adopted a short wake/sleep cycle (150/75 min) resulting in a low sleep pressure condition to counteract the homeostatic pressure and investigate the circadian process. Performances were evaluated by a simple reaction time task and a Go/Nogo task repeated every 3H45. RESULTS: In the SD condition, inhibitory motor control (i.e., ability to inhibit an inappropriate response) was impaired by extended wakefulness equally in both age groups (P<.01). Sustained attention (i.e. ability to respond accurately to appropriate stimuli) on the executive task decreased under sleep deprivation in both groups, and even more in young participants (P<.05). In the NAP condition, age did not influence the time course of inhibitory motor control or sustained attention. In the SD and NAP conditions, older participants had a less fluctuating reaction time performance across time of day than young participants (P<.001). CONCLUSION: Aging could be a protective factor against the effects of extended wakefulness especially on sustained attention failures due to an attenuation of sleep pressure with duration of time awake.