ALBERT

Description: Human presence in space, whether permanent or temporary, is accompanied by the presence of microbes. However, the extent of microbial changes in response to spaceflight conditions and the corresponding changes to infectious disease risk is unclear. Previous studies have indicated that spaceflight weakens the immune system in humans and animals. In addition, preflight and in-flight monitoring of the International Space Station (ISS) and other spacecraft indicates the presence of opportunistic pathogens and the potential of obligate pathogens. Altered antibiotic resistance of microbes in flight has also been shown. As astronauts and cosmonauts live for longer periods in a closed environment, especially one using recycled water and air, there is an increased risk to crewmembers of infectious disease events occurring in-flight. Therefore, understanding how the space environment affects microorganisms and their disease potential is critically important for spaceflight missions and requires further study. The goal of this flight experiment, operationally called MICROBE, is to utilize three model microbial pathogens, Salmonella typhimurium, Pseudomonas aeruginosa, and Candida albicans to examine the global effects of spaceflight on microbial gene expression and virulence attributes. Specifically, the aims are (1) to perform microarray-mediated gene expression profiling of S. typhimurium, P. aeruginosa, and C. albicans, in response to spaceflight in comparison to ground controls and (2) to determine the effect of spaceflight on the virulence potential of these microorganisms immediately following their return from spaceflight using murine models. The model microorganisms were selected as they have been isolated from preflight or in-flight monitoring, represent different degrees of pathogenic behavior, are well characterized, and have sequenced genomes with available microarrays. In particular, extensive studies of S. typhimurium by the Principal Investigator, Dr. Nickerson, using ground-based analog systems demonstrate important changes in the genotypic, phenotypic, and virulence characteristics of this pathogen resulting from exposure to a flight-like environment (i.e. modeled microgravity).

Description: Testing of the HSCT Generation 2.0 nozzle model hardware was conducted at the Boeing Low Speed Aeroacoustic Facility, LSAF. Concurrent measurements of noise and thrust were made at critical takeoff design conditions for a variety of mixer/ejector model hardware. Design variables such as suppressor area ratio, mixer area ratio, liner type and thickness, ejector length, lobe penetration, and mixer chute shape were tested. Parallel testing was conducted at G.E.'s Cell 41 acoustic free jet facility to augment the LSAF test. The results from the Gen 2.0 testing are being used to help shape the current nozzle baseline configuration and guide the efforts in the upcoming Generation 2.5 and 3.0 nozzle tests. The Gen 2.0 results have been included in the total airplane system studies conducted at MDC and Boeing to provide updated noise and thrust performance estimates.

Description: As logistical access for in-flight space research becomes more limited, the use of ground based spaceflight analogs for life science studies will increase. These studies are particularly important as NASA progresses towards the Lunar and eventually Mars missions outlined in the 2005 Vision for Space Exploration. Countermeasures must be developed to mitigate the clinical risks associated with exploration class space missions. In an effort to coordinate studies across multiple disciplines, NASA has selected 90-day bed rest as the analog of choice, and initiated the Flight Analogs Project to implement research studies with or without the evaluation of countermeasures. Although bed rest is not the analog of choice to evaluate spaceflight-associated immune dysfunction, a standard Immune Assessment was developed for subjects participating in the 90-day bed best studies. The Immune Assessment consists of: leukocyte subset distribution, T cell functional responses, intracellular cytokine production profiles, latent viral reactivation, virus specific T cell levels, virus specific T cell function, stress hormone levels and a behavioral assessment using stress questionnaires. The purpose of the assessment during the initial studies (without countermeasure) is to establish control data against which future studies (with countermeasure) will be evaluated. It is believed that some of the countermeasures planned to be evaluated in future studies, such as exercise, pharmacologic intervention or nutritional supplementation, have the ability to impact immune function. Therefore immunity will likely be monitored during those studies. The data generated during the first three control studies showed that the subjects in general did not display altered peripheral leukocyte subsets, constitutive immune activation, significant latent viral reactivation (EBV, VZV) or altered T cell function. Interestingly, for some subjects the level of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) both decreased during the studies. This likely reflects the isolation of the subjects (from an immunological perspective) and absence of everyday subclinical challenges to the immune system. Cortisol levels (plasma and saliva) did not vary significantly during the studies. This probably reflects a lack of physiological stress during the study and the stress of readaptation to the 1xG environment at R+1. These data demonstrate the absence of significant immune alteration during 90-day bed rest, and establish control data against which future studies (including countermeasures) may be compared.

Description: A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

Description: Thermoregulation in the space environment is critical for survival, especially in off- nominal operations. In such cases, mathematical models of thermoregulation are frequently employed to evaluate safety-of-flight issues in various human mission scenarious. In this study, the 225-node Wissler model and the 41-Node Metabolic Man model are employed to evaluate the effects of such a scenario. Metabolic loads on astronauts wearing the advanced crew escape suit (ACES) and liquid cooled ventilation garment (LCVG) are imposed on astronauts exposed to elevated cabin temperatures resulting from a systems failure. The study indicates that the performance of the ACES/LCVG cooling system is marginal. Increases in workload and or cabin temperature above nominal will increase rectal temperature, stored heat load, heart rate, and sweating, which could lead to deficits in the performance of cognitive and motor tasks. This is of concern as the ACES/LCVG is employed during Shuttle decent when the likelihood of a safe landing may be compromised. The study indicates that the most effective mitigation strategy would be to decrease the LCVG inlet temperature.

Description: On April 19, 2008 the crew of Expedition 16 left the International Space Station and returned to earth via their Soyuz TMA-11 capsule after 192 days on orbit. Their capsule experienced the second consecutive and third ballistic reentry in the last 10 TMA recoveries and landed approximately 260 miles (420 km) from the prime landing site. Issues: The purpose of this presentation will be to describe, not only the typical medical operational challenges faced by Flight Surgeons recovering a long duration crew from space, but also address the unique challenges that existed with the Expedition 16 landing and crew recovery. Nominal Soyuz recovery challenges include remote recovery sites with crew exposures to sleep shifting and fatigue, dehydration, hypothermia and hyperthermia, and rotational, sustained, and impact g-forces. These environmental factors coupled with the patho-physiologic neuro-vestibular and orthostatic intolerance changes that occur secondary to the crews reintroduction into the earth s gravity field will be detailed. Additional challenges that were unique to this expedition included a ballistic reentry with higher g-loads, the presence of fire outside of the capsule on landing, a contingency medical event of a ground support personnel, and loss of communications with the crew just prior to landing and during recovery operations. Conclusions: In spite of these unique challenges the Russian Search and Rescue Forces and Medical Support personnel along with U.S. Medical Support performed well together. Possible improvements in training and coordination will be discussed.

Description: Promethazine (PMZ) is the drug of choice for the treatment of symptoms associated with space motion sickness in astronauts. Side effects of PMZ include sedation, dizziness and cognitive performance impairment. In this study, we examined pharmacodynamics (PD) in human subjects and validated methods for evaluating cognitive performance effects of medications in space. METHODS: PMZ (12.5,25, and 50 mg) or placebo was administered by IM injection to human subjects in a randomized double-blind treatment design. Samples and data were collected for 72 h post dose. PD evaluation was performed using a battery of performance tests administered using WinSCAT (Windows based Space Cognitive Assessment Test) on a laptop computer, and ARES (ANAM Readiness Evaluation System) on a PDA, plasma concentrations of PMZ were measured using a LC-MS method. RESULTS: Results indicate a linear correlation between PMZ concentration and cognitive performance parameters (p〈0.01). Test accuracy decreased and test completion time and response time increased significantly with increasing plasma PMZ concentration. CONCLUSIONS: These results suggest a concentration dependent decrement in cognitive performance associated with PMZ. WinSCAT and ARES are sensitive tools for the assessment PMZ PD and may be applicable for such evaluations with other neurocognitive drugs.

Description: NASA plans to build an outpost on the Moon for prolonged human habitation and research. The lunar surface is covered by a layer of soil, of which the finest portion is highly reactive dust. NASA has invited NIOSH to collaboratively investigate the toxicity of lunar dust. Dust samples of respirable sizes were aerodynamically isolated from two lunar soil samples of different maturities (cosmic exposure ages) collected during the Apollo 16 mission. The lunar dust samples, titanium dioxide, or quartz, suspended in normal saline or in Survanta (a bovine lung surfactant), were given to groups of 5 mice (C-57 male) by intrapharyngeal aspiration at 1, 0.3, or 0.1 mg/mouse. The mice were euthanized 7 or 30 days later, and their lungs were lavaged to assess the toxicity biomarkers in bronchioalveolar lavage fluids. The acellular fractions were assayed for total proteins, lactate dehydrogenase activities, and cytokines; the cellular portions were assessed for total cell counts and cell differentials. Results from the high-dose groups showed that lunar dust, suspended in saline, was more toxic than TiO 2, but less toxic than quartz. Lunar dust particles aggregate and settle out rapidly in water or saline, but not in Survanta. Lunar dust suspended in Survanta manifested greater toxicity than lunar dust in saline. The increase in toxicity presumably was due to that Survanta gave a better particle dispersion in the lungs. The two lunar dust samples showed similar toxicity. The overall results showed that lunar dust is more toxic than TiO 2 but less toxic than quartz.

Description: Back pain is frequently reported by astronauts during the early phase of space flight as they adapt to the microgravity environment. However, the epidemiology of space adaptation back pain has not been well defined. The purpose of this retrospective study was to develop a case definition of space adaptation back pain, determine the incidence of space adaptation back pain, and determine the effectiveness of available treatments. Medical records from the Mercury, Apollo, Apollo-Soyuz Test Project (ASTP), Skylab, Mir, International Space Station (ISS), and Shuttle programs were reviewed. All episodes of in-flight back pain that met the criteria for space adaptation back pain were recorded. Pain characteristics, including intensity, location, and duration of the pain were noted. The effectiveness of specific treatments also was recorded. The incidence of space adaptation back pain among astronauts was determined to be 53% (384/722). Most of the affected astronauts reported mild pain (85%). Moderate pain was reported by 11% of the affected astronauts and severe pain was reported by only 4% of the affected astronauts. The most effective treatments were fetal positioning (91% effective) and the use of analgesic medications (85% effective). This retrospective study aids in the development of a case definition of space adaptation back pain and examines the epidemiology of space adaptation back pain. Space adaptation back pain is usually mild and self-limited. However, there is a risk of functional impairment and mission impact in cases of moderate or severe pain that do not respond to currently available treatments. Therefore, the development of preventive measures and more effective treatments should be pursued.