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Spatz J.M.,Beth Israel Deaconess Medical Center | Spatz J.M.,Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology | Spatz J.M.,Massachusetts General Hospital | Fields E.E.,Enterprise Advisory Services | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Objective: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest. Design, Setting, and Participants: Seven healthy adult men (31 ± 3 yr old) underwent 90 d of 6° head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center. Outcomes: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption we reevaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean ± SD. Results: Consistent with prior reports, bone mineral density declined significantly (1-2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 ±20%; P = 0.003) and BR-60 (+42 ± 31%; P < 0.001), with a lesser increase at BR-90 (+22 ± 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (-17 ± 16%; P = 0.02) and BR-60 (-24 ± 14%; P = 0.03) and remained lower than BL at BR-90 (-21 ± 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01). Conclusions: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased. Copyright © 2012 by The Endocrine Society.


Mehta S.K.,Enterprise Advisory Services Inc. | Crucian B.E.,NASA | Stowe R.P.,Microgen Laboratories | Simpson R.J.,University of Houston | And 3 more authors.
Cytokine | Year: 2013

Success of long duration space missions will depend upon robust immunity. Decreased immunity has been observed in astronauts during short duration missions, as evident by the reactivation of latent herpes viruses. Seventeen astronauts were studied for reactivation and shedding of latent herpes viruses before, during, and after 9-14. days of 8 spaceflights. Blood, urine, and saliva samples were collected 10. days before the flight (L-10), during the flight (saliva only), 2-3. h after landing (R. +. 0), 3. days after landing (R. +. 3), and 120. days after landing (R. +. 120). Values at R. +. 120 were used as baseline levels. No shedding of viruses occurred before flight, but 9 of the 17 (designated " virus shedders" ) shed at least one or more viruses during and after flight. The remaining 8 astronauts did not shed any of the 3 target viruses (non-virus shedders). Virus-shedders showed elevations in 10 plasma cytokines (IL-1α, IL-6, IL-8, IFNγ, IL-4, IL-10, IL-12, IL-13, eotaxin, and IP-10) at R. +. 0 over baseline values. Only IL-4 and IP-10 were elevated in plasma of non-virus shedders. In virus shedders, plasma IL-4 (a Th2 cytokine) was elevated 21-fold at R. +. 0, whereas IFNγ (a Th1 cytokine) was elevated only 2-fold indicating a Th2 shift. The inflammatory cytokine IL-6 was elevated 33-fold at R. +. 0. In non-shedding astronauts at R. +. 0, only IL-4 and IP-10 levels were elevated over baseline values. Elevated cytokines began returning to normal by R. +. 3, and by R. +. 120 all except IL-4 had returned to baseline values. These data show an association between elevated plasma cytokines and increased viral reactivation in astronauts. © 2012.


Mehta S.K.,Enterprise Advisory Services Inc. | Laudenslager M.L.,University of Colorado at Denver | Stowe R.P.,Microgen Laboratories | Crucian B.E.,NASA | And 2 more authors.
Brain, Behavior, and Immunity | Year: 2014

Latent virus reactivation and diurnal salivary cortisol and dehydroepiandrosterone were measured prospectively in 17 astronauts (16 male and 1 female) before, during, and after short-duration (12-16. days) Space Shuttle missions. Blood, urine, and saliva samples were collected during each of these phases. Antiviral antibodies and viral load (DNA) were measured for Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). Three astronauts did not shed any virus in any of their samples collected before, during, or after flight. EBV was shed in the saliva in all of the remaining 14 astronauts during all 3 phases of flight. Seven of the 14 EBV-shedding subjects also shed VZV during and after the flight in their saliva samples, and 8 of 14 EBV-shedders also shed CMV in their urine samples before, during, and after flight. In 6 of 14 crewmembers, all 3 target viruses were shed during one or more flight phases. Both EBV and VZV DNA copies were elevated during the flight phase relative to preflight or post-flight levels. EBV DNA in peripheral blood was increased preflight relative to post-flight. Eighteen healthy controls were also included in the study. Approximately 2-5% of controls shed EBV while none shed VZV or CMV. Salivary cortisol measured preflight and during flight were elevated relative to post-flight. In contrast DHEA decreased during the flight phase relative to both preflight and post-flight. As a consequence, the molar ratio of the area under the diurnal curve of cortisol to DHEA with respect to ground (AUCg) increased significantly during flight. This ratio was unrelated to viral shedding. In summary, three herpes viruses can reactivate individually or in combination during spaceflight. © 2014 Elsevier Inc..


Smith S.M.,Johnson Space Center | Heer M.,University of Bonn | Heer M.,Profil Institute for Metabolic Research GmbH | Wang Z.,Enterprise Advisory Services | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss. Objective: The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle. Design: Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies. Setting: Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented. Participants: All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects. Main Outcome Measures: Serum total, free, and bioavailable testosterone were measured along with serumandurinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG. Results: Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P < 0.01) on landing day after these flights and after short-duration space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone. Conclusions: There was no evidence for decrements in testosterone during long-duration space flight or bed rest. Copyright © 2012 by The Endocrine Society.


Zwart S.R.,Universities Space Research Association | Booth S.L.,Tufts University | Peterson J.W.,Tufts University | Wang Z.,Enterprise Advisory Services Inc. | Smith S.M.,NASA
Journal of Bone and Mineral Research | Year: 2011

Bone loss is a well-documented change during and after long-duration spaceflight. Many types of countermeasures to bone loss have been proposed, including vitamin K supplementation. The objective of this series of studies was to measure change in vitamin K status in response to microgravity under a variety of spaceflight and spaceflight analog (model) conditions, including long-duration spaceflight studies (n = 15), three bed rest studies (n = 15, 49, and 24), and a 14-day saturation dive (n = 6). In crew members who flew 2-6 months on the International Space Station, in-flight and postflight plasma phylloquinone concentrations were unchanged from the preflight mean. Consistent with this finding, urinary Î-carboxyglutamic acid (GLA), a measure of vitamin K-dependent protein turnover, did not change in response to flight. Serum undercarboxylated osteocalcin (%ucOC), a measure of vitamin K function, was generally unchanged in response to flight. Spaceflight findings were corroborated by findings of no changes in phylloquinone, urinary GLA, or %ucOC during or after bed rest in three separate bed rest studies (21-90 days in duration) or after a 14-day saturation dive. The data presented here do not support either a need for vitamin K supplementation during spaceflight or the suggestion of using vitamin K as a bone loss countermeasure in spaceflight. © 2011 American Society for Bone and Mineral Research.


Birlea M.,Aurora University | Cohrs R.J.,Aurora University | Bos N.,Aurora University | Mehta S.K.,Enterprise Advisory Services | And 2 more authors.
Journal of Medical Virology | Year: 2014

All neurological and ocular complications of varicella zoster virus (VZV) reactivation can occur without rash. Virological verification requires detection of VZV DNA or anti-VZV IgG antibody in cerebrospinal fluid (CSF), or anti-VZV IgM antibody in serum or CSF. If VZV were readily detected in other tissue in patients with neurological disease without rash and found to correlate with tests listed above, more invasive tests such as lumbar puncture might be obviated. Saliva is a potential source of VZV DNA. To study the potential diagnostic value of detecting VZV DNA in saliva from patients with neurological disease, saliva of healthy adults was searched for VZV DNA. A single saliva sample obtained by passive drool was centrifuged at 16,000g for 20min. DNA was extracted from the supernatant and cell pellet and examined in triplicate for VZV DNA by real time PCR. A single random saliva sample from 80 healthy men and women aged 20-59 years revealed no VZV DNA (Table), but was uniformly positive for cell (GAPdH) DNA. Because VZV DNA was not found in a random saliva sample from 80 individuals 20-59-year-old, a VZV-positive sample during neurologic disease may have potential significance. Further studies will determine whether VZV DNA in saliva correlates with VZV DNA or anti-VZV antibody in CSF in patients with neurological disease. © 2013 Wiley Periodicals, Inc.


Zwart S.R.,Universities Space Research Association | Mehta S.K.,Enterprise Advisory Services | Ploutz-Snyder R.,Universities Space Research Association | Bourbeau Y.,Enterprise Advisory Services | And 3 more authors.
Journal of Nutrition | Year: 2011

Maintaining vitamin D status without sunlight exposure is difficult without supplementation. This study was designed to better understand interrelationships between periodic vitamin D supplementation and immune function in Antarctic workers. The effect of 2 oral dosing regimens of vitamin D supplementation on vitamin D status and markers of immune function was evaluated in people in Antarctica with no UV light exposure for 6 mo. Participants were given a 2000-IU (50 μg) daily (n = 15) or 10,000-IU (250 μg) weekly (n = 14) vitamin D supplement for 6 mo during a winter in Antarctica. Biological samples were collected at baseline and at 3 and 6 mo. Vitamin D intake, markers of vitamin D and bone metabolism, and latent virus reactivation were determined. After 6 mo, the serum 25-hydroxyvitamin D concentration (mean ± SD) increased from 56 ± 17 to 79 ± 16 nmol/L and from 52 ± 10 to 69 ± 9 nmol/L in the 2000-IU/d and 10,000-IU/wk groups, respectively (main effect over time, P <0.001). Participants with a greater BMI (participant BMI range = 19-43 g/m2) had a smaller increase in 25-hydroxyvitamin D after 6-mo supplementation (P < 0.05). Participants with high serum cortisol and higher serum 25-hydroxyvitamin D were less likely to shed Epstein-Barr virus in saliva (P < 0.05). The doses given raised vitamin D status in participants not exposed to sunlight for 6 mo, and the efficacy was influenced by baseline vitamin D status and BMI. The data also provide evidence that vitamin D, interacting with stress, can reduce risk of latent virus reactivation during the winter in Antarctica. © 2011 American Society for Nutrition.


Zwart S.R.,Universities Space Research Association | Pierson D.,NASA | Mehta S.,Enterprise Advisory Services | Gonda S.,NASA | Smith S.M.,NASA
Journal of Bone and Mineral Research | Year: 2010

NF-κB is a transcriptional activator of many genes, including some that lead to muscle atrophy and bone resorption - significant concerns for astronauts. NF-κB activation is inhibited by eicosapentaenoic acid (EPA), but the influence of this omega-3 fatty acid on the effects of weightlessness are unknown. We report here cellular, ground analogue, and spaceflight findings. We investigated the effects of EPA on differentiation of RAW264.7 monocyte/macrophage cells induced by receptor activator of NF-κB ligand (RANKL) and on activation of NF-κB by tumor necrosis factor α (TNF-α) or exposure to modeled weightlessness. EPA (50 μM for 24 hours) inhibited RANKL-induced differentiation and decreased activation of NF-κB induced by 0.2 μg/mL of TNF-α for 30 minutes or by modeled weightlessness for 24 hours (p<.05). In human studies, we evaluated whether NF-κB activation was altered after short-duration spaceflight and determined the relationship between intake of omega-3 fatty acids and markers of bone resorption during bed rest and the relationship between fish intake and bone mineral density after long-duration spaceflight. NF-κB was elevated in crew members after short-duration spaceflight, and higher consumption of fish (a rich source of omega-3 fatty acids) was associated with reduced loss of bone mineral density after flight (p<.05). Also supporting the cell study findings, a higher intake of omega-3 fatty acids was associated with less N-telopeptide excretion during bed rest (Pearson r=-0.62, p<.05). Together these data provide mechanistic cellular and preliminary human evidence of the potential for EPA to counteract bone loss associated with spaceflight. © 2010 American Society for Bone and Mineral Research. 2010 ASBMR.


Wong W.C.,Enterprise Advisory Services Incorporated
Biofouling | Year: 2010

As the provision of potable water is critical for successful habitation of the International Space Station (ISS), life support systems were installed in December 2008 to recycle both humidity from the atmosphere and urine to conserve available water in the Station. In-flight pre-consumption testing from the dispensing needle at the Potable Water Dispenser (PWD) indicated that bacterial concentrations exceeded the current ISS specifications of 50 colony-forming units (CFU) ml(-1). Subsequent investigations revealed that a corrugated stainless steel flex hose upstream of the dispensing needle in the PWD was filled with nonsterile water and left at room temperature for more than 1 month before launch. To simulate biofilm formation that was suspected in the flight system, sterile flex hoses were seeded with a consortium of bacterial isolates previously recovered from other ISS water systems, including Ralstonia pickettii, Burkholderia multivorans, Caulobacter vibrioides, and Cupriavidus pauculus. After incubation for 5 days, the hoses were challenged with various chemical disinfectants including hydrogen peroxide (H2O2), colloidal silver, and buffered pH solutions to determine the ability of the disinfectants to decrease and maintain bacterial concentrations below ISS specifications. The disinfection efficacy over time was measured by collecting daily heterotrophic plate counts after exposure to the disinfectants. A single flush with either 6% H2O2 solution or a mixture of 3% H2O2 and 400 ppb colloidal silver effectively reduced the bacterial concentrations to <1 CFU ml(-1) for a period of up to 3 months.


Grant
Agency: National Aeronautics and Space Administration | Branch: | Program: STTR | Phase: Phase I | Award Amount: 123.02K | Year: 2016

The multi-months duration and energy constraints of the Earth?Mars journey are forcing an evolution toward the self-sufficiency of human crews in their readiness to adapt to changing circumstances and survive emergencies so far from Earth. The situation is akin to the one faced by the first waves of people brave enough to explore new continents during the course of human history. Limited by the capabilities of their ship or caravan on a long journey, their fate was inevitably tied to their ability to learn, adapt, and use their new environment and its resources as quickly as possible. The planned In Situ Resource Utilization (ISRU) can yield tangible benefits for NASA pioneering missions currently studied under the Evolvable Mars Campaign. Robotic explorations have now established the wide distribution of water in the Martian subsurface with large variations in concentrations and geological contexts (ice-rock mixtures, polyhydrated minerals). Mining and processing Martian water-bearing minerals may prove key to the ultimate success of long stays on Mars via life support and chemical synthesis of methane ascent fuel and oxygen. The prospect of exploring, developing, and exploiting mineral reserves on another planetary body evokes many technical and economic challenges, which often lead to decision paralysis in strategic planners willing to consider ISRU in deep-space missions. This Phase I work will provide NASA with a comprehensive modeling tool built to describe the processes of Off-Earth mining and materials processing in their geological context and deliver comparative technical and economic results on the optimized operations and technologies. It is a unique innovative tool built on the expertise and best practices of the terrestrial mining industry in synergy with expert space technologists in ISRU. It will provide NASA decision-makers with a means to identify and correlate major gaps in knowledge to plan technology investments and knowledge-gathering missions

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