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Exercise training is a key countermeasure used to offset spaceflight-induced multisystem deconditioning. Here, we evaluated the effects of exercise countermeasures on multisystem function in a large cohort (N = 46) of astronauts on long-duration spaceflight missions. We found that during 178 ± 48 d of spaceflight, ~600 min/wk of aerobic and resistance exercise did not fully protect against multisystem deconditioning. However, substantial inter-individual heterogeneity in multisystem response was apparent with changes from pre to postflight ranging from -30% to +5%. We estimated that up to 17% of astronauts would experience performance-limiting deconditioning if current exercise countermeasures were used on future spaceflight missions. These findings support the need for refinement of current countermeasures, adjunct interventions, or enhanced requirements for preflight physiologic and functional capacity for the protection of astronaut health and performance during exploration missions to the moon and beyond., (© 2023. The Author(s).)

The effect of confined and isolated experience on astronauts' health is an important factor to consider for future space exploration missions. The more confined and isolated humans are, the more likely they are to develop negative behavioral or cognitive conditions such as a mood decline, sleep disorder, depression, fatigue and/or physiological problems associated with chronic stress. Molecular mediators of chronic stress, such as cytokines, stress hormones or reactive oxygen species (ROS) are known to induce cellular damage including damage to the DNA. In view of the growing evidence of chronic stress-induced DNA damage, we conducted an explorative study and measured DNA strand breaks in 20 healthy adults. The participants were grouped into five teams (missions). Each team was composed of four participants, who spent 45 days in isolation and confinement in NASA's Human Exploration Research Analog (HERA). Endogenous DNA integrity, ex-vivo radiation-induced DNA damage and the rates of DNA repair were assessed every week. Our results show a high inter-individual variability as well as differences between the missions, which cannot be explained by inter-individual variability alone. The ages and sex of the participants did not appear to influence the results.

One of the major concerns for long-term exploration missions beyond the Earth's magnetosphere is consequences from exposures to solar particle event (SPE) protons and galactic cosmic rays (GCR). For long-term crewed Lunar and Mars explorations, the production of fresh food in space will provide both nutritional supplements and psychological benefits to the astronauts. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of two different compositions of charged particles-simulated GCR, and simulated SPE protons on dry and hydrated seeds of the model plant Arabidopsis thaliana and the crop plant Mizuna mustard [ Brassica rapa var. japonica ]. Exposures to charged particles, simulated GCRs (up to 80 cGy) or SPEs (up to 200 cGy), were performed either acutely or at a low dose rate using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Control and irradiated seeds were planted in a solid phytogel and grown in a controlled environment. Five to seven days after planting, morphological parameters were measured to evaluate radiation-induced damage in the seedlings. After exposure to single types of charged particles, as well as to simulated GCR, the hydrated Arabidopsis seeds showed dose- and quality-dependent responses, with heavier ions causing more severe defects. Seeds exposed to simulated GCR (dry seeds) and SPE (hydrated seeds) had significant, although much less damage than seeds exposed to heavier and higher linear energy transfer (LET) particles. In general, the extent of damage depends on the seed type.

The incidence of presyncopal events is high soon after a long-duration spaceflight;>60% of returning astronauts could not complete a 10-min 80° head-up tilt test on landing day (R+0) after ~6 months of spaceflight. The objective of this study was to demonstrate the ability of a lower body gradient compression garment (GCG) to protect against an excessive increase in heart rate and a decrease in blood pressure during standing after long-duration spaceflight. Methods : Eleven astronauts (9 M, 2 F) volunteered to participate. The stand test protocol consisted of 2 min of prone rest followed by 3.5 min of standing. Subjects completed one familiarization session, two preflight data collection sessions in standard clothing, and three tests on landing day while wearing GCG. Postflight tests were conducted 1-4 h (R+0A), ~12 h (R+0B), and ~28 h after landing (R+0C). Results : All astronauts completed the stand test preflight. Three astronauts were unable to attempt the stand test at R+0A, and one of these was unable to start the test at R+0B. One astronaut was unable to complete 3.5 min of standing at R+0B (test ended at 3.3 min). Review of the individual's blood pressure data revealed no hypotension but the astronaut reported significant motion sickness. Of the astronauts who participated in testing on landing day, the heart rate and mean arterial pressure responses to standing (stand-prone) were not different than preflight at any of the postflight sessions. Conclusion : Wearing the GCG after spaceflight prevented the tachycardia that normally occurs while standing after spaceflight without compression garments and protected against a decrease in blood pressure during a short stand test., (Copyright © 2020 Lee, Ribeiro, Laurie, Feiveson, Kitov, Kofman, Macias, Rosenberg, Rukavishnikov, Tomilovskaya, Bloomberg, Kozlovskaya, Reschke and Stenger.)

Spaceflight missions expose astronauts to increased risk of oxidative stress and inflammatory damage that might accelerate the development of asymptomatic cardiovascular disease. The purpose of this investigation was to determine whether long-duration spaceflight (>4 mo) results in structural and functional changes in the carotid and brachial arteries. Common carotid artery (CCA) intima-media thickness (cIMT), CCA distensibility and stiffness, and brachial artery endothelium-dependent and -independent vasodilation were measured in 13 astronauts (10 men, 3 women) ~180 and 60 days before launch, during the mission on ~15, 60, and 160 days of spaceflight, and within 1 wk after landing. Biomarkers of oxidative stress and inflammation were measured at corresponding times in fasting blood samples and urine samples from 24- or 48-h pools. Biomarkers of oxidative stress and inflammation increased during spaceflight, but most returned to preflight levels within 1 wk of landing. Mean cIMT, CCA stiffness, and distensibility were not significantly different from preflight at any time. As a group, neither mean endothelium-dependent nor -independent vasodilation changed from preflight to postflight, but changes within individuals in endothelial function related to some biomarkers of oxidative stress. Whereas biomarkers of oxidative stress and inflammation are elevated during spaceflight, CCA and brachial artery structure and function were not changed by spaceflight. It is unclear whether future exploration missions, with an extended duration in altered gravity fields and higher radiation exposure, may be problematic. NEW & NOTEWORTHY Carotid artery structure and stiffness did not change on average in astronauts during long-duration spaceflight (<12 mo), despite increased oxidative stress and inflammation. Most oxidative stress and inflammation biomarkers returned to preflight levels soon after landing. Brachial artery structure and function also were unchanged by spaceflight. In this group of healthy middle-aged male and female astronauts, spaceflight in low Earth orbit does not appear to increase long-term cardiovascular health risk.

The implementation of rotating-wall vessels (RWVs) for studying the effect of lack of gravity has attracted attention, especially in the fields of stem cells, tissue regeneration, and cancer research. Immune cells incubated in RWVs exhibit several features of immunosuppression including impaired leukocyte proliferation, cytokine responses, and antibody production. Interestingly, stress hormones influence cellular immune pathways affected by microgravity, such as cell proliferation, apoptosis, DNA repair, and T cell activation. These pathways are crucial defense mechanisms that protect the cell from toxins, pathogens, and radiation. Despite the importance of the adrenergic receptor in regulating the immune system, the effect of microgravity on the adrenergic system has been poorly studied. Thus, we elected to investigate the synergistic effects of isoproterenol (a sympathomimetic drug), radiation, and microgravity in nonstimulated immune cells. Peripheral blood mononuclear cells were treated with the sympathomimetic drug isoproterenol, exposed to 0.8 or 2 Gy γ-radiation, and incubated in RWVs. Mixed model regression analyses showed significant synergistic effects on the expression of the β2-adrenergic receptor gene (ADRB2). Radiation alone increased ADRB2 expression, and cells incubated in microgravity had more DNA strand breaks than cells incubated in normal gravity. We observed radiation-induced cytokine production only in microgravity. Prior treatment with isoproterenol clearly prevents most of the microgravity-mediated effects. RWVs may be a useful tool to provide insight into novel regulatory pathways, providing benefit not only to astronauts but also to patients suffering from immune disorders or undergoing radiotherapy.

Among the many stressors astronauts are exposed to during spaceflight, cosmic radiation may lead to various serious health effects. Specifically, space radiation may contribute to decreased immunity, which has been documented in astronauts during short- and long-duration missions, as evidenced by several changes in cellular immunity and plasma cytokine levels. Reactivation of latent herpes viruses, either directly from radiation of latently infected cells and/or from perturbation of the immune system, may result in disease in astronauts. Epstein‒Barr virus (EBV) is one of the eight human herpes viruses known to infect more than 90% of human adults and persists for the life of the host without normally causing adverse effects. Reactivation of several latent viruses in astronauts is well documented, although the mechanism of reactivation is not well understood. We studied the effect of four different types of radiation, (1) 137 Cs gamma rays, (2) 150-MeV protons, (3) 600 MeV/n carbon ions, and (4) 600 MeV/n iron ions on the activation of lytic gene transcription and of reactivation of EBV in a latently infected cell line (Akata) at doses of 0.1, 0.5, 1.0, and 2.0 Gy. The data showed that for all doses used in this study, lytic gene transcription was induced and median viral loads were significantly higher for all types of radiation than in corresponding control samples, with the increases detected as early as four days post-exposure and generally tapering off at later time points. The viability and size of EBV-infected Akata cells were highly variable and exhibited approximately the same trend in time for all radiation types at 0.1, 0.5, 1.0, and 2.0 Gy. This work shows that reactivation of viruses can occur due to the effect of different types of radiation on latently infected cells in the absence of changes or cytokines produced in the immune system. In general, gamma rays are more effective than protons, carbon ions, and iron ions in inducing latent virus reactivation, though these high-energy particles did induce more sustained and later reactivation of EBV lytic gene transcription. These findings also challenge the common relative biological effectiveness concept that is often used in radiobiology for other end points.

Introduction: Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits., Methods: A test battery comprised of seven functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular, and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 d of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included control and exercise groups to examine the effects of exercise during bed rest., Results: Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased HR to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function; however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects., Conclusion: Bed rest data indicate that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular functions, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance.

Introduction: The purpose of this study was to determine how short- and long-duration spaceflight affects astronauts' performance on functional tests that challenge the balance control system (Seated Egress and Walk; Object Translation; Recovery from Fall/Stand; and Jump Down) and on clinical tests of balance function (Computerized Dynamic Posturography and Tandem Walk). In addition, we examined how exercise affects functional performance after long-term axial body unloading during 70 d of bed rest at 6° head-down tilt., Methods: Data were collected twice during the 2-mo period before spaceflight or during the 2-wk period before bed rest, and four times after flight or bed rest: on the day of landing or the day bed rest ended, 1 d and 6 d later, and a final session 12 d after bed rest or 30 d after spaceflight., Results: For bed rest subjects, long-term axial unloading alone caused functional performance deficits immediately after bed rest. However, the addition of an exercise regimen did not significantly improve median functional performance immediately after this axial unloading. For spaceflight subjects, the length of the space mission was directly related to the severity of functional performance deficits within 1 d of landing and during the subsequent recovery period after flight., Discussion: The performance data suggest that an additional sensorimotor-based countermeasure may be necessary to maintain functional performance at preflight levels immediately after spaceflight.Miller CA, Kofman IS, Brady RR, May-Phillips TR, Batson CD, Lawrence EL, Taylor LC, Peters BT, Mulavara AP, Feiveson AH, Reschke MF, Bloomberg JJ. Functional task and balance performance in bed rest subjects and astronauts. Aerosp Med Hum Perform. 2018; 89(9):805-815.

Introduction: The effects of repeated centrifugation in association with head-down tilt (HDT) bed rest (BR) on the mediation of basic reflexes associated with the major postural muscles was investigated as a potential countermeasure for maintaining balance control and neuromotor reflex function., Methods: There were 15 male volunteers who were exposed to 21 d of 6° HDT-BR. Eight were treated with daily 1-h artificial gravity (AG) exposures aboard a short radius centrifuge that provided 1-g footward loading at heart level. The other seven served as HDT-BR control subjects. Balance control was assessed using a standard computerized dynamic posturography (CDP) protocol that was modified by adding low-frequency pitch-plane head movements. Neuromotor reflex function was assessed using tendon stretch reflexes (MSR) and functional stretch reflex (FSR) data collected from the triceps surae muscle group., Results: CDP performance was degraded by HDT-BR in both groups (ranging from 24 to 26%), but was unaffected by AG. BR also degraded MSR and FSR functions in both groups, with increased peak reflex latencies between 1.5 and 1.95 ms, but AG maintained pre-BR latencies for the MSR subjects., Discussion: AG exposure did not modify balance control from pre-BR responses, but did help prevent decrements in FSR latencies post-BR.Paloski WH, Reschke MF, Feiveson AH. Bed rest and intermittent centrifugation effects on human balance and neuromotor reflexes. Aerosp Med Hum Perform. 2017; 88(9):812-818.

Reactivation of latent herpes viruses was measured in 23 astronauts (18 male and 5 female) before, during, and after long-duration (up to 180 days) spaceflight onboard the international space station . Twenty age-matched and sex-matched healthy ground-based subjects were included as a control group. Blood, urine, and saliva samples were collected before, during, and after spaceflight. Saliva was analyzed for Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus type 1. Urine was analyzed for cytomegalovirus. One astronaut did not shed any targeted virus in samples collected during the three mission phases. Shedding of Epstein-Barr virus, varicella-zoster virus, and cytomegalovirus was detected in 8 of the 23 astronauts. These viruses reactivated independently of each other. Reactivation of Epstein-Barr virus, varicella-zoster virus, and cytomegalovirus increased in frequency, duration, and amplitude (viral copy numbers) when compared to short duration (10 to 16 days) space shuttle missions. No evidence of reactivation of herpes simplex virus type 1, herpes simplex virus type 2, or human herpes virus 6 was found. The mean diurnal trajectory of salivary cortisol changed significantly during flight as compared to before flight ( P  = 0.010). There was no statistically significant difference in levels of plasma cortisol or dehydoepiandosterone concentrations among time points before, during, and after flight for these international space station crew members, although observed cortisol levels were lower at the mid and late-flight time points. The data confirm that astronauts undertaking long-duration spaceflight experience both increased latent viral reactivation and changes in diurnal trajectory of salivary cortisol concentrations.

Leg muscle mass and strength are decreased during reduced activity and non-weight-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., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Introduction: Cardiovascular deconditioning apparently progresses with flight duration, resulting in a greater incidence of orthostatic intolerance following long-duration missions. Therefore, we anticipated that the proportion of astronauts who could not complete an orthostatic tilt test (OTT) would be higher on landing day and the number of days to recover greater after International Space Station (ISS) than after Space Shuttle missions., Methods: There were 20 ISS and 65 Shuttle astronauts who participated in 10-min 80° head-up tilt tests 10 d before launch, on landing day (R+0), and 3 d after landing (R+3). Fisher's Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the OTT. Cox regression was used to identify cardiovascular parameters associated with OTT completion and mixed model analysis was used to compare the change and recovery rates between groups., Results: The proportion of astronauts who completed the OTT on R+0 (2 of 6) was less in ISS than in Shuttle astronauts (52 of 65). On R+3, 13 of 15 and 19 of 19 of the ISS and Shuttle astronauts, respectively, completed the OTT. An index comprised of stroke volume and diastolic blood pressure provided a good prediction of OTT completion and was altered by spaceflight similarly for both astronaut groups, but recovery was slower in ISS than in Shuttle astronauts., Conclusions: The proportion of ISS astronauts who could not complete the OTT on R+0 was greater and the recovery rate slower after ISS compared to Shuttle missions. Thus, mission planners and crew surgeons should anticipate the need to tailor scheduled activities and level of medical support to accommodate protracted recovery after long-duration microgravity exposures.

Introduction: Aerobic deconditioning may occur during International Space Station (ISS) flights. This paper documents findings from exercise testing conducted before, during, and after ISS expeditions., Methods: There were 30 male and 7 female astronauts on ISS missions (48 to 219 d, mean 163 d) who performed cycle exercise protocols consisting of 5-min stages eliciting 25%, 50%, and 75% peak oxygen uptake (Vo(2peak)). Tests were conducted 30 to 90 d before missions, on flight day 15 and every 30 flight days thereafter, and on recovery (R) days +5 and +30. During pre- and postflight tests, heart rate (HR) and metabolic gas exchange were measured. During flight, extrapolation of the HR and Vo2 relationship to preflight-measured peak HR provided an estimate of Vo(2peak), referred to as the aerobic capacity index (ACI)., Results: HR during each exercise stage was elevated (P < 0.05) and oxygen pulse was reduced (P < 0.05) on R+5 compared to preflight; however, no other metabolic gas analysis values significantly changed. Compared to preflight, the ACI declined (P < 0.001) on R+5, but recovered to levels greater than preflight by R+30 (P = 0.008). During flight, ACI decreased below preflight values, but increased with mission duration (P < 0.001)., Conclusions: Aerobic deconditioning likely occurs initially during flight, but ACI recovers toward preflight levels as flight duration increases, presumably due to performance of exercise countermeasures. Elevated HR and lowered oxygen pulse on R+5 likely results from some combination of relative hypovolemia, lowered cardiac stroke volume, reduced cardiac distensibility, and anemia, but recovery occurs by R+30.

Introduction: The Hypobaric Decompression Sickness (DCS) Treatment Model links a decrease in computed bubble volume from increased pressure (ΔP), increased oxygen (O2) partial pressure, and passage of time during treatment to the probability of symptom resolution [P(SR)]. The decrease in offending volume is realized in two stages: 1) during compression via Boyles law; and 2) during subsequent dissolution of the gas phase via the oxygen window., Methods: We established an empirical model for the P(SR) while accounting for multiple symptoms within subjects. The data consisted of 154 cases of hypobaric DCS symptoms with ancillary information from tests on 56 men and 18 women., Results: Our best estimated model is P(SR)=1/(1+exp(-(ln(ΔP)-1.510+0.795×AMB-0.00308×Ts)/0.478)), where ΔP is pressure difference (psid); AMB=1 if ambulation took place during part of the altitude exposure, otherwise AMB=0; and Ts is the elapsed time in minutes from the start of altitude exposure to recognition of a DCS symptom., Discussion: Values of ΔP as inputs to the model would be calculated from the Tissue Bubble Dynamics Model based on the effective treatment pressure: ΔP=P2-P1|=P1×V1/V2-P1, where V1 is the computed volume of a bubble at low pressure P1 and V2 is computed volume after a change to a higher pressure P2. If 100% ground-level oxygen was breathed in place of air, then V2 continues to decrease through time at P2 at a faster rate.

This investigation was designed to measure aerobic capacity (V̇o2peak) during and after long-duration International Space Station (ISS) missions. Astronauts (9 males, 5 females: 49 ± 5 yr, 77.2 ± 15.1 kg, 40.6 ± 6.4 ml·kg(-1)·min(-1) [mean ± SD]) performed peak cycle tests ∼90 days before flight, 15 days after launch, every ∼30 days in-flight, and on recovery days 1 (R + 1), R + 10, and R + 30. Expired metabolic gas fractions, ventilation, and heart rate (HR) were measured. Data were analyzed using mixed-model linear regression. The main findings of this study were that V̇o2peak decreased early in-flight (∼17%) then gradually increased during flight but never returned to preflight levels. V̇o2peak was lower on R + 1 and R + 10 than preflight but recovered by R + 30. Peak HR was not different from preflight at any time during or following flight. A sustained decrease in V̇o2peak during and/or early postflight was not a universal finding in this study, since seven astronauts were able to attain their preflight V̇o2peak levels either at some time during flight or on R + 1. Four of these astronauts performed in-flight exercise at higher intensities compared with those who experienced a decline in V̇o2peak, and three had low aerobic capacities before flight. These data indicate that, while V̇o2peak may be difficult to maintain during long-duration ISS missions, aerobic deconditioning is not an inevitable consequence of long-duration spaceflight., (Copyright © 2014 the American Physiological Society.)

The objectives of this study were to evaluate the efficacy of two separate countermeasures, exercise and protein supplementation, to prevent muscle strength and lean tissue mass losses during 60 days of bed rest (BR) in women and whether countermeasure efficacy was influenced by pre-BR muscular fitness (strength, endurance, tissue mass). Twenty-four women were assigned to an exercise (EX, n = 8), a no-exercise control (CON, n = 8), or a no-exercise protein supplementation group (PROT, n = 8). EX performed supine treadmill exercise within lower body negative pressure 3-4 days/wk and maximal concentric and eccentric supine leg- and calf-press exercises 2-4 days/wk. PROT consumed a diet with elevated protein content compared with CON and EX (1.6 vs. 1.0 g·kg(-1)·day(-1)). Knee and calf isokinetic strength and endurance, isotonic leg-press strength, and leg lean mass were measured before and after BR. Post-BR knee extensor strength and endurance, ankle strength, and leg lean mass were significantly greater and leg-press strength tended to be higher in EX than in CON and PROT. Post-BR measures in PROT were not different than those in CON. Exercise countermeasure efficacy was less, and strength, endurance, and leg lean mass losses in CON and PROT were greater, in subjects who were more fit pre-BR. An exercise protocol combining resistive and aerobic exercise training protects against losses in strength, endurance, and leg lean mass in women during BR, while a nutritional countermeasure without exercise was not effective. Exercise countermeasures may require individualization to protect higher levels of strength and endurance.

Knowledge of a patient's cardiac age, or "heart age", could prove useful to both patients and physicians for better encouraging lifestyle changes potentially beneficial for cardiovascular health. This may be particularly true for patients who exhibit symptoms but who test negative for cardiac pathology. We developed a statistical model, using a Bayesian approach, that predicts an individual's heart age based on his/her electrocardiogram (ECG). The model is tailored to healthy individuals, with no known risk factors, who are at least 20 years old and for whom a resting ~5 min 12-lead ECG has been obtained. We evaluated the model using a database of ECGs from 776 such individuals. Secondarily, we also applied the model to other groups of individuals who had received 5-min ECGs, including 221 with risk factors for cardiac disease, 441 with overt cardiac disease diagnosed by clinical imaging tests, and a smaller group of highly endurance-trained athletes. Model-related heart age predictions in healthy non-athletes tended to center around body age, whereas about three-fourths of the subjects with risk factors and nearly all patients with proven heart diseases had higher predicted heart ages than true body ages. The model also predicted somewhat higher heart ages than body ages in a majority of highly endurance-trained athletes, potentially consistent with possible fibrotic or other anomalies recently noted in such individuals.

VZV reactivation produces zoster (shingles) which may be further complicated by meningoencephalitis, myelopathy, vasculopathy and multiple ocular disorders. Importantly, these neurological and ocular complications of VZV reactivation can occur without rash. In such instances, virological verification relies on detection of VZV DNA or anti-VZV IgG antibody in cerebrospinal fluid (CSF), or less often, the presence of VZV DNA in blood mononuclear cells or anti-VZV IgM antibody in serum or CSF. If VZV were readily detected in other tissue samples (e.g., saliva or tears) in patients with neurological disease in the absence of rash and shown to correlate with the standard tests listed above, more invasive tests such as lumbar puncture might be obviated. In patients with acute herpes zoster, the yield of cell DNA was greater in saliva collected by passive drool or synthetic swab than by cotton swab. The time to process saliva from collection to obtaining DNA was 1h. VZV DNA was present exclusively in the pelleted fraction of saliva and was found in 100% of patients before antiviral treatment. This rapid sensitive method can be applied readily to saliva from humans with neurologic and other disease that might be caused by VZV in the absence of rash., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: The fitting of probabilistic decompression sickness (DCS) models is more effective when data encompass a wide range of DCS incidence. We obtained such data from the Air Force Research Laboratory Altitude Decompression Sickness Research Database. The data are results from 29 tests comprising 708 human altitude chamber exposures (536 men and 172 women). There were 340 DCS outcomes with per-test DCS incidence ranging from 0 to 88%. The tests were characterized by direct ascent at a rate of 5000 ft x min(-1) (1524 m x min(-1)) to a range of altitudes (226 to 378 mmHg) for 4 h after prebreathe times of varying length and with varying degrees of physical activity while at altitude., Methods: Logistic regression was used to develop an expression for the probability of DCS [P(DCS)] using the Hill equation with decompression dose as the main predictor. Here, decompression dose is defined in terms of either the tissue ratio (TR) or a bubble growth index (BGI). Other predictors in the model were gender and peak exercise intensity at altitude., Results: All three predictors (decompression dose, gender, and exercise intensity) were important contributions to the model for P(DCS)., Discussion: Higher TR or BGI, male gender, and higher exercise intensity at altitude all increased the modeled decompression dose. Using either TR or BGI to define decompression dose provided comparable results, suggesting that a simple TR is adequate for simple altitude exposures as an abstraction of the true decompression dose. The model is primarily heuristic and limits estimates of P(DCS) to only a 4-h exposure.

The NASA Study of Cataract in Astronauts (NASCA) was designed to measure the impact of exposure to space radiation on progression rates of cortical, nuclear, and posterior subcapsular cataract in U.S. astronauts who have flown in space and comparison groups of astronauts who had not flown in space, and subjects with a history of military aviation. We present our analyses of 5 years of data with an average of 3.8 exams per subject. All subjects had digital lens images with the Nidek EAS 1000 Lens Imaging System. Because of high variability and skewness of opacity measures, nonparametric methods were used to test for association between rates of opacification and space radiation exposure. First, median regression was used to collapse longitudinal data into robust estimates of progression rates (opacity severity compare to time for each eye of each subject). To quantify and test for a radiation effect, median regression with the dependent variable being the maximum of the two slopes (OD and OS) per subject was then used, adjusting for the confounding variables of age, nutritional, and sun-exposure histories. Median regression showed evidence of an association between the rate of cortical progression in the worse eye with radiation dose and age. The estimated median progression rate from space radiation being 0.25 ± 0.13% lens area/Sv/year (P = 0.062). We found no relationship between radiation exposure and progression of aggregate area of posterior subcapsular cataract or nuclear progression rates. However, longer follow-up may be needed to further understand any impact of space radiation on progression rates for posterior subcapsular cataracts and nuclear cataracts, and to characterize changes to visual acuity.

Background: The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, nasal congestion, and headache. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and under the influence of thigh occlusion cuffs available as a countermeasure device (Braslet cuffs)., Methods: Nine International Space Station crewmember subjects (expeditions 16-20) were examined in 15 experiment sessions 101 ± 46 days after launch (mean ± SD; 33-185). Twenty-seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs (162 parameter states/session). Quality of cardiac and vascular ultrasound examinations was assured through remote monitoring and guidance by investigators from the NASA Telescience Center in Houston, TX, and the Mission Control Center in Korolyov, Moscow region, Russia., Results: 14 of 81 conditions (27 parameters measured at baseline, Valsalva, and Mueller maneuver) were significantly different when the Braslet was applied. Seven of 27 parameters were found to respond differently to respiratory maneuvers depending on the presence or absence of thigh compression., Conclusions: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an effective tool in determining the volume status of a cardiac or hemodynamically compromised patient at the "microgravity bedside."

Objectives: This study investigated whether it is feasible to use sonography to monitor changes in the optic nerve sheath diameter in a porcine model., Methods: A fiber-optic intracranial pressure transducer was surgically placed through the frontal sinus directly into the brain parenchyma of adult Yorkshire pigs (n = 5). A second bolt was placed on the contralateral side for intraparenchymal fluid infusion. Optic nerve sheath diameter measurements were acquired by each of 2 ultrasound operators around the leading edge of the nerve, 3 to 5 mm distal from the origin of the optic nerve. To induce a change in diameter, intracranial pressure was manipulated by injecting normal saline into the intraparenchymal infusion catheter located in the symmetric contralateral position as the pressure-monitoring probe., Results: Data from 1 pig were unusable because of a cerebrospinal fluid leak into the sinus and orbital fissure. Saline aliquots of 1 to 10 mL were able to generate intracranial pressures typically starting from 10 to 15 mm Hg and increasing to 75 to 90 mm Hg, which eventually evoked a Cushing response. Fluid injection was controlled to increase pressures by 60 mm Hg over a 15- to 20-minute period. Regression analysis of all animals showed that the optic nerve sheath diameter increased by 0.0034 mm/mm Hg of intracranial pressure; however, this slope ranged from 0.0025 to 0.0046, depending on the animal measured. There was no discernible effect of the ultrasound operator on the slope; however, measurements made by 1 operator were consistently higher than the others by about 8% of the overall diameter range., Conclusions: These results suggest that the use of the optic nerve sheath diameter to noninvasively confirm acute changes in intracranial pressure over 1 hour is feasible in a porcine model. We recommend that this method be validated in humans using direct intracranial pressure measurement where possible to confirm it as a screening tool for acute and chronically increased diameters secondary to elevated pressure in clinical settings.

In an NASA ground study, two forms of cognitive tests were evaluated in terms of their sensitivity to sleepiness induced by the drug promethazine (PMZ). Performance for the two test modes (Y(1) and Y(2)), PMZ concentration, and a self-reported sleepiness using the Karolinska Sleepiness Scale (KSS) were monitored for 12 h post dose. A problem arises when using KSS to establish an association between true sleepiness and performance because KSS scores are discrete and also because they tend to concentrate on certain values. Therefore, we define a latent sleepiness measure X as an unobserved continuous random variable describing a subject's actual state of sleepiness. Under the assumption that drug concentration affects X, which then affects Y(1), Y(2), and KSS, we use Bayesian methods to estimate joint equations that permit unbiased comparison of the performance measures' sensitivity to X. The equations incorporate subject random effects and include a negativity constraint on subject-specific slopes of performance with respect to sleepiness.

Introduction: Astronauts face transient disruptions of sensorimotor functions after spaceflight. Computerized dynamic posturography (CDP) testing has been used to document functional recovery; however, its objective value in return-to-duty decision-making has not been established. Therefore, we studied the diagnostic accuracy of CDP to determine the most effective test components for probing post-spaceflight sensorimotor deficits., Methods: There were 11 first-time astronauts and 11 matched controls who were evaluated by CDP before and after spaceflight (controls did not fly). All CDP testing was conducted with eyes closed while standing on a computer-controlled force plate. Somatosensory influences were either unperturbed (stationary force plate) or altered (unstable force plate), and vestibular influences were either unperturbed (head erect) or altered by static (head pitched forward or back by 200) or dynamic (head pitched voluntarily in cadence with an auditory signal: +/- 20 degrees at 0.33 Hz) challenges. Using equilibrium (EQ) scores derived from peak A-P sway as the dependent measure, we determined the sensitivity and specificity of each test condition and then constructed receiver operator characteristic (ROC) curves to determine their diagnostic accuracies., Results: The greatest diagnostic accuracy was obtained from the test requiring the subject to make dynamic head movements while standing on an unstable force plate (94.9% sensitivity 96.6% specificity, area under ROC curve = 0.991). By contrast, the estimated ROC area for the standard clinical Romberg test (fixed support, head erect), which is often used to make postflight return-to-duty decisions, was 0.718., Conclusion: We recommend that results from this test paradigm be considered during postflight return-to-duty decision-making.

Background: Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a approximately 5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG., Methods: Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals., Results: Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84%) to 92% (88-96%) (P < 0.0001) while also increasing specificity from 85% (77-91%) to 94% (88-98%) (P < 0.05). In diseased patients, another 5-parameter A-ECG score increased the PPV of ECG for LVSD from 53% (41-65%) to 92% (78-98%) (P < 0.0001) without compromising related negative predictive value., Conclusion: Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.

Introduction: Astronauts have complained of back pain occurring during spaceflight, presumably due to the elongation of the spine from the lack of gravity. Herniated nucleus pulposus (HNP) is known to occur in aviators exposed to high Gz and has been diagnosed in several astronauts in the immediate post-spaceflight period. It is unknown whether astronauts exposed to microgravity are at added risk for developing HNP in the post-spaceflight period due to possible in-flight intervertebral disc changes., Methods: For a preset study period, incidence rates of HNP were compared between the U.S. astronaut population and a matched control population not involved in spaceflight using the Longitudinal Study of Astronaut Health database. Using a Weibull survival model, time trends of the risk of HNP prior to and after spaceflight were compared within the astronaut group. HNP incidences in other populations that have previously been reported in the literature were also compared with results in this study., Results: The incidence of HNP was 4.3 times higher in the U.S. astronaut population (N=321) compared to matched controls (N=983) not involved in spaceflight. For astronauts, there was relatively more HNP in the cervical region of the spine (18 of 44) than for controls (3 of 35); however, there was no clear increase of HNP incidence in those astronauts who were high performance jet aircraft pilots. There was evidence suggesting that the risk is increased immediately after spaceflight., Conclusions: Astronauts are at higher risk of incurring HNP, especially immediately following spaceflight.

Astronauts returning from space flight and performing Earth-bound activities must rapidly transition from the microgravity-adapted sensorimotor state to that of Earth's gravity. The goal of the current study was to assess locomotor dysfunction and recovery of function after long-duration space flight using a test of functional mobility. Eighteen International Space Station crewmembers experiencing an average flight duration of 185 days performed the functional mobility test (FMT) pre-flight and post-flight. To perform the FMT, subjects walked at a self selected pace through an obstacle course consisting of several pylons and obstacles set up on a base of 10-cm-thick, medium-density foam for a total of six trials per test session. The primary outcome measure was the time to complete the course (TCC, in seconds). To assess the long-term recovery trend of locomotor function after return from space flight, a multilevel exponential recovery model was fitted to the log-transformed TCC data. All crewmembers exhibited altered locomotor function after space flight, with a median 48% increase in the TCC. From the fitted model we calculated that a typical subject would recover to 95% of his/her pre-flight level at approximately 15 days post-flight. In addition, to assess the early motor learning responses after returning from space flight, we modeled performance over the six trials during the first post-flight session by a similar multilevel exponential relation. We found a significant positive correlation between measures of long-term recovery and early motor learning (P < 0.001) obtained from the respective models. We concluded that two types of recovery processes influence an astronaut's ability to re-adapt to Earth's gravity environment. Early motor learning helps astronauts make rapid modifications in their motor control strategies during the first hours after landing. Further, this early motor learning appears to reinforce the adaptive realignment, facilitating re-adaptation to Earth's 1-g environment on return from space flight.

The NASA Study of Cataract in Astronauts (NASCA) is a 5-year longitudinal study of the effect of space radiation exposure on the severity/progression of nuclear, cortical and posterior subcapsular (PSC) lens opacities. Here we report on baseline data that will be used over the course of the longitudinal study. Participants include 171 consenting astronauts who flew at least one mission in space and a comparison group made up of three components: (a) 53 astronauts who had not flown in space, (b) 95 military aircrew personnel, and (c) 99 non-aircrew ground-based comparison subjects. Continuous measures of nuclear, cortical and PSC lens opacities were derived from Nidek EAS 1000 digitized images. Age, demographics, general health, nutritional intake and solar ocular exposure were measured at baseline. Astronauts who flew at least one mission were matched to comparison subjects using propensity scores based on demographic characteristics and medical history stratified by gender and smoking (ever/never). The cross-sectional data for matched subjects were analyzed by fitting customized non-normal regression models to examine the effect of space radiation on each measure of opacity. The variability and median of cortical cataracts were significantly higher for exposed astronauts than for nonexposed astronauts and comparison subjects with similar ages (P=0.015). Galactic cosmic space radiation (GCR) may be linked to increased PSC area (P=0.056) and the number of PSC centers (P=0.095). Within the astronaut group, PSC size was greater in subjects with higher space radiation doses (P=0.016). No association was found between space radiation and nuclear cataracts. Cross-sectional data analysis revealed a small deleterious effect of space radiation for cortical cataracts and possibly for PSC cataracts. These results suggest increased cataract risks at smaller radiation doses than have been reported previously.

We report results from a study designed to explore the utility of artificial gravity (AG) as a countermeasure to bone loss induced by microgravity simulation. After baseline testing, 15 male subjects underwent 21 days of 6 degrees head-down bed rest to simulate the deconditioning associated with spaceflight. Eight of the subjects underwent 1 h of centrifugation (AG; 1 G(z) at the heart, 2.5 G(z) at the feet) each day for 21 days, whereas seven of the subjects served as untreated controls (Con). Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density (BMD) and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry and peripheral quantitative computerized tomography before and after bed rest. Urinary excretion of bone resorption markers increased during bed rest, but the AG and Con groups did not differ significantly. The same was true for serum C-telopeptide. During bed rest, bone alkaline phosphatase (ALP) and total ALP tended to be lower in the AG group (P = 0.08, P = 0.09). Neither BMC nor BMD changed significantly from the pre-bed rest period in AG or Con groups, and the two groups were not significantly different. However, when AG and Con data were combined, there was a significant (P < 0.05) effect of time for whole body total BMC and total hip and trochanter BMD. These data failed to demonstrate efficacy of this AG prescription to prevent the changes in bone metabolism observed during 3 wk of bed rest.

For future space missions outside of the Earth's magnetic field, the risk of radiation exposure from solar particle events (SPEs) during extra-vehicular activities (EVAs) or in lightly shielded vehicles is a major concern when designing radiation protection including determining sufficient shielding requirements for astronauts and hardware. While the expected frequency of SPEs is strongly influenced by solar modulation, SPE occurrences themselves are chaotic in nature. We report on a probabilistic modeling approach, where a cumulative expected occurrence curve of SPEs for a typical solar cycle was formed from a non-homogeneous Poisson process model fitted to a database of proton fluence measurements of SPEs that occurred during the past 5 solar cycles (19-23) and those of large SPEs identified from impulsive nitrate enhancements in polar ice. From the fitted model, we then estimated the expected frequency of SPEs at any given proton fluence threshold with energy >30 MeV (Phi(30)) during a defined space mission period. Analytic energy spectra of 34 large SPEs observed in the space era were fitted over broad energy ranges extending to GeV, and subsequently used to calculate the distribution of mGy equivalent (mGy-Eq) dose for a typical blood-forming organ (BFO) inside a spacecraft as a function of total Phi(30) fluence. This distribution was combined with a simulation of SPE events using the Poisson model to estimate the probability of the BFO dose exceeding the NASA 30-d limit of 250 mGy-Eq per 30 d. These results will be useful in implementing probabilistic risk assessment approaches at NASA and guidelines for protection systems for astronauts on future space exploration missions.

Introduction: Spaceflight has functionally significant effects on sensorimotor behavior, but it is difficult to separate the effects of ascending somatosensory changes caused by postural muscle and plantar surface unloading from descending visual-vestibular neural changes. To differentiate somatosensory changes from graviceptor changes in post-spaceflight sensorimotor behavior, bed rest may serve as an exclusionary analog to spaceflight., Methods: Four separate tests were used to measure changes in sensorimotor performance: 1) the monosynaptic stretch reflex (MSR); 2) the functional stretch reflex (FSR); 3) balance control parameters associated with computerized dynamic posturography (CDP); and 4) a functional mobility test (FMT)., Results: A mixed model regression analysis showed significant increases in median MSR start and peak latencies, while the median FSR latency showed no significant increase. Median MSR peak magnitude showed a significant increase during the middle bed rest period (19-60 d). There were no significant effects of bed rest on balance control, but some indication that dynamic head movements may affect posture after bed rest. Time to complete the course for the FMT increased significantly with bed rest., Discussion: The four primary tests indicate that long-duration head-down bed rest, through unloading and modification of the body's support surface, serves as an exclusionary analog for sensorimotor responses to spaceflight. Furthermore, the data suggest that procedures designed to alleviate modifications to the sensory substrate serving the soles of the feet may provide a countermeasure to help maintain support afferentation of the postural muscles.

Gait kinematics have been shown to vary with speed and visual-target fixation distance, but their combined effects on toe trajectory during treadmill walking are not known. The purpose of this investigation was to determine the role of walking speed and target distance on vertical toe trajectory during treadmill walking. Subjects walked on a treadmill at five speeds while performing a dynamic visual-acuity task at both "far" and "near" target distances (ten trials total). The analysis concentrated on three specific toe trajectory events during swing: the first peak toe height just after toe-off; the minimum toe height (toe clearance), and the second peak toe height just before heel strike. With increasing speed, toe clearance decreased and the peak toe height just before heel strike increased. Only the peak toe height just after toe-off was significantly changed between the near-target and far-target tasks, though the difference was small. Therefore, walking speed and visual-fixation distance cannot be neglected in the analysis of toe trajectory. Otherwise, differences observed between populations may be attributed to age- or clinically related factors, instead of disparities of speed or target-fixation distance.

Objective: To identify electrocardiographic predictors of mortality in patients with familial dysautonomia (FD)., Methods: Ten-minute resting high-fidelity 12-lead electrocardiograms (ECGs) were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict mortality over a subsequent 4.5-year period, including representative parameters of heart rate variability (HRV), QT variability (QTV), T-wave complexity, signal averaged ECG, and 3-dimensional ECG., Results: Four of the 14 FD patients died during the follow-up period, three with concomitant pulmonary disorder. Of the ECG parameters studied, increased non-HRV-correlated QTV and decreased HRV were the most predictive of death. Compared to controls as a group, FD patients also had significantly increased ECG voltages, JTc intervals and waveform complexity, suggestive of structural heart disease., Conclusion: Increased QTV and decreased HRV are markers for increased risk of death in FD patients. When present, both markers may reflect concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea.

Fifty-four patients with herpes zoster were treated with valacyclovir. On treatment days 1, 8, and 15, pain was scored and saliva examined for varicella-zoster virus (VZV) DNA. VZV DNA was found in every patient the day treatment was started and later disappeared in 82%. There was a positive correlation between the presence of VZV DNA and pain and between VZV DNA copy number and pain (P <.0005). VZV DNA was present in 1 patient before rash and in 4 after pain resolved and was not present in any of 6 subjects with chronic pain or in 14 healthy subjects. Analysis of human saliva has potential usefulness in the diagnosis of neurological disease produced by VZV without rash.

Background: Prospective testing of denitrogenation protocols to reduce the risk of decompression sickness (DCS) in astronauts requires pre-defined accept and reject criteria. We assume that the end-point of a test, the presence or absence of signs and symptoms attributable to DCS, is unequivocal. However, diagnosis of DCS is not perfect, nor is there is a gold standard to assess diagnosis error rates. These error rates could cause consistent bias in the decision to accept or reject proposed protocols. We used a Latent Class Model (LCM) incorporating inter-rater agreement to estimate false-positive and negative rates of DCS diagnosis for each of six symptomatic (covariate) strata., Methods: Case descriptions from 135 reports collected since 1982 were available with 103 diagnosed as DCS (73.1%). There were 3 subsets of 45 descriptions that were randomly selected, information about the original diagnosis omitted, and were sent to 15 physicians (raters), all experts in altitude DCS. Subsets were diagnosed for DCS by either four, five, or six raters. We then used a LCM to estimate false-positive and false-negative error rates for the original NASA test diagnosis, even though a gold standard was not available., Results: Estimates of false-positive rates in the NASA diagnoses ranged from 13% to 83% and from 1% to 32% for false-negative rates over the six strata of symptomatic response variables., Conclusions: Our findings suggest that use of current DCS diagnostic outcomes as if they were error free would likely produce an inflated rejection rate of acceptable protocols in future testing if adjustments are not made.

Electrocardiographic repolarization abnormalities characterized by T-wave morphology parameters such as the principal component analysis ratio and the relative and the absolute T-wave residuum (TWR(rel) and TWR(abs)) are predictive of cardiovascular and/or all-cause mortality. However, when using a "10-second median beat" for analysis, the reported mean values for TWR(rel) vary widely and parameter reproducibility is somewhat suspect. In repeated electrocardiographic recordings conducted 1 month and 1 year apart on 15 and 27 healthy individuals, respectively, we studied the said T-wave morphology parameters in single complexes and in reduced noise signal averages containing 10 and 200 complexes. Considering all subjects, the mean (+/-SD) TWR(rel) was highest in a single complex (0.0345% +/- 0.0183%), intermediate in the 10-beat signal-averaged complexes (0.0125% +/- 0.0051%), and lowest in the 200-beat signal-averaged complexes (0.0078% +/- 0.0036%) (P < .0001), with the same trend also observed in the TWR(abs) but not in the principal component analysis ratio. Reproducibility as quantified by within-subject variance and reliability as quantified by the intraclass (intrasubject) correlation coefficient also improved as the number of T-wave complexes analyzed increased. We conclude that signal averages consisting of more than 10 complexes (or more than 10 seconds worth of complexes) are required to produce reproducible and reliable values for TWR(rel) and TWR(abs).

Because changes in the 12-lead high-frequency QRS electrocardiogram (HF QRS ECG) more sensitively identify myocardial ischemia than do changes in the ST segments of the conventional ECG, it is important that changes in HF QRS signals that are merely physiological be distinguishable from those that are potentially pathological. We therefore studied the temporal variation of HF QRS measures such as root mean square (RMS) voltage and the presence vs absence of reduced amplitude zones (RAZs) in 107 asymptomatic individuals in the supine position during a brief period of ECG monitoring. In addition, to ascertain the effects of posture on the 12-lead HF QRS ECG, we collected additional seated data from 25 of these individuals and estimated the fifth and 95th percentile of the percent relative change between the supine and seated measurements. In all cases, variation of HF QRS parameters decreased as the number of beats in the signal average increased. For example, in the supine position, the 95th percentile of the percent relative change between consecutive within-lead measurements of RMS voltage for a 50-beat signal average was 12.3% but decreased to 11.7%, 11.2%, and 10.7% for 75, 100, and 150 beat signal averages, respectively (P < .01). After transition from the supine to the seated upright position, changes in some measures of HF QRS were statistically significant, with RMS voltage decreasing significantly in lead V3 and with the number of RAZs lost in the 12-lead HF QRS ECG significantly exceeding the number of RAZs gained. We conclude that most measures of HF QRS ECG are sufficiently stable for routine continuous monitoring.

To better understand the effects of varying head movement frequencies on human balance control, 12 healthy adult humans were studied during static and dynamic (0.14, 0.33, 0.6 Hz) head tilts of +/- 30 degrees in the pitch and roll planes. Postural sway was measured during upright stance with eyes closed and altered somatosensory inputs provided by a computerized dynamic posturography (CDP) system. Subjects were able to maintain upright stance with static head tilts, although postural sway was increased during neck extension. Postural stability was decreased during dynamic head tilts, and the degree of destabilization varied directly with increasing frequency of head tilt. In the absence of vision and accurate foot support surface inputs, postural stability may be compromised during dynamic head tilts due to a decreased ability of the vestibular system to discern the orientation of gravity. This instability may compound the risk of falling following recovery from balance disorders or adaptation to altered gravity conditions such as space flight. Thus, dynamic head tilts may improve the diagnostic sensitivity of computerized dynamic posturography, particularly for healthy subjects recovering from temporary balance control deficits.

Background: Astronaut spacewalk training can result in a variety of symptom complaints and possible injuries. This study quantified and characterized signs, symptoms, and injuries resulting from extravehicular activity spacesuit training at NASA's Neutral Buoyancy Laboratory, Johnson Space Center, Houston, TX, immersion facility., Methods: We identified the frequency and incidence of symptoms by location, mechanisms of injury, and effective countermeasures. Recommendations were made to improve injury prevention, astronaut training, test preparation, and training hardware. At the end of each test, a questionnaire was completed documenting signs and symptoms, mechanisms of injury, and countermeasures., Results: Of the 770 tests, there were 190 in which suit symptoms were reported (24.6%). There were a total of 352 reported suit symptom comments. Of those symptoms, 166 were in the hands (47.16%), 73 were in the shoulders (20.7%), and 40 were in the feet (11.4%). Others ranged from 6.0% to 0.28%, respectively, from the legs, arms, neck, trunk, groin, and head. Causal mechanisms for the hands included moisture and hard glove contacts resulting in fingernail injuries; in the shoulders, hard contact with suit components and strain mechanisms; and in the feet, hard boot contact. The severity of symptoms was highest in the shoulders, hands, and feet., Conclusions: Most signs and symptoms were mild, self-limited, of brief duration, and were well controlled by available countermeasures. Some represented the potential for significant injury with consequences affecting astronaut health and performance. Correction of extravehicular activity training-related injuries requires a multidisciplinary approach to improve prevention, medical intervention, astronaut training, test planning, and suit engineering.

High frequency electrocardiography analyzing the entire QRS complex in the frequency range of 150 to 250 Hz may prove useful in the detection of coronary artery disease, yet the long-term stability of these waveforms has not been fully characterized. Therefore, we prospectively investigated the reproducibility of the root mean squared voltage, kurtosis, and the presence versus absence of reduced amplitude zones in signal averaged 12-lead high frequency QRS recordings acquired in the supine position one month apart in 16 subjects and one year apart in 27 subjects. Reproducibility of root mean squared voltage and kurtosis was excellent over these time intervals in the limb leads, and acceptable in the precordial leads using both the V-lead and CR-lead derivations. The relative error of root mean squared voltage was 12% month-to-month and 16% year-to-year in the serial recordings when averaged over all 12 leads. Reduced amplitude zones were also reproducible up to a rate of 87% and 81%, respectively, for the month-to-month and year-to-year recordings. We conclude that 12-lead high frequency QRS electrocardiograms are sufficiently reproducible for clinical use.

Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

Computerized dynamic posturography (CDP) is widely used for assessment of altered balance control. CDP trials are quantified using the equilibrium score (ES), which ranges from zero to 100, as a decreasing function of peak sway angle. The problem of how best to model and analyze ESs from a controlled study is considered. The ES often exhibits a skewed distribution in repeated trials, which can lead to incorrect inference when applying standard regression or analysis of variance models. Furthermore, CDP trials are terminated when a patient loses balance. In these situations, the ES is not observable, but is assigned the lowest possible score--zero. As a result, the response variable has a mixed discrete-continuous distribution, further compromising inference obtained by standard statistical methods. Here, we develop alternative methodology for analyzing ESs under a stochastic model extending the ES to a continuous latent random variable that always exists, but is unobserved in the event of a fall. Loss of balance occurs conditionally, with probability depending on the realized latent ES. After fitting the model by a form of quasi-maximum-likelihood, one may perform statistical inference to assess the effects of explanatory variables. An example is provided, using data from the NIH/NIA Baltimore Longitudinal Study on Aging.

In response to exercise performed before or after altitude decompression, physiological changes are suspected to affect the formation and growth of decompression bubbles. We hypothesized that the work to change the size of a bubble is done by gas pressure gradients in a macro- and microsystem of thermodynamic forces and that the number of bubbles formed through time follows a Poisson process. We modeled the influence of tissue O(2) consumption on bubble dynamics in the O(2) transport system in series against resistances, from the alveolus to the microsystem containing the bubble and its surrounding tissue shell. Realistic simulations of experimental decompression procedures typical of actual extravehicular activities were obtained. Results suggest that exercise-induced elevation of O(2) consumption at altitude leads to bubble persistence in tissues. At the same time, exercise-enhanced perfusion leads to an overall suppression of bubble growth. The total volume of bubbles would be reduced unless increased tissue motion simultaneously raises the rate of bubble formation through cavitation processes, thus maintaining or increasing total bubble volume, despite the exercise.

For altitude decompressions, we hypothesized that reported onset times of limb decompression illness (DCI) pain symptoms follow a probability distribution related to total bubble volume [V(b.)(t)] as a function of time. Furthermore, we hypothesized that the probability of ever experiencing DCI during a decompression is associated with the cumulative volume of bubbles formed. To test these hypotheses, we first used our previously developed formation-and-growth model (Am J Physiol Regulatory Integrative Comp Physiol 279: R2304-R2316, 2000) to simulate Vb.(t) for 20 decompression profiles in which 334 human subjects performed moderate repetitive skeletal muscle exercise (827 kJ/h) in an altitude chamber. Using survival analysis, we determined that, for a controlled condition of exercise, the fraction of the subject population susceptible to DCI can be approximately expressed as a power function of the formation-and-growth model-predicted cumulative volume of bubbles throughout the altitude exposure. Furthermore, for this fraction, the probability density distribution of DCI onset times is approximately equal to the ratio of the time course of formation-and growth-modeled total bubble volume to the predicted cumulative volume.

The reactivation of cytomegalovirus (CMV) in 71 astronauts was investigated, using polymerase chain reaction. A significantly greater (P<.0001) shedding frequency was found in urine samples from astronauts before spaceflight (10.6%) than in urine from the healthy control subject group (1.2%). Two of 4 astronauts studied during spaceflight shed CMV in urine. A significant increase (P<.0001) in CMV antibody titer, compared with baseline values, was also found 10 days before spaceflight. CMV antibody titer was further increased (P<.001) 3 days after landing, compared with 10 days before the mission. Significant increases in stress hormones were also found after landing. These results demonstrate that CMV reactivation occurred in astronauts before spaceflight and indicate that CMV may further reactivate during spaceflight.