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AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.

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STUDY OBJECTIVES: Prescription sleep aids are frequently used in the general population and even more frequently in spaceflight. To evaluate the risk to operational safety, a ground-based, double-blind, placebo-controlled study on the emergent awakening effects of zolpidem and zaleplon was conducted. METHODS: N = 34 participants (age M = 42.1 ± 9.7; 25 males; 9 Astronauts, 7 Astronaut candidates, and 18 Flight Controllers) were investigated for three nights separated by M = 10 days. They were randomized to ingestion of one of the following at lights out: placebo, 10 mg zaleplon, and either 5 mg (N = 20) or 10 mg (N = 14) zolpidem. They were awakened abruptly by alarm at the expected PK,max (1 hr after lights out for zaleplon; 1.5 hr for placebo/zolpidem). Participants were required to turn off the alarm and perform a cognitive test battery twice, separated by a 20-30 min reading break. They then returned to sleep and were awakened to perform the same cognitive tasks at an average of 6.7 hr after drug ingestion. RESULTS: Relative to placebo, the effects of 10 mg zaleplon and 5 mg zolpidem on cognitive performance were minor. In contrast, 10 mg zolpidem adversely affected cognitive throughput (p < 0.001), psychomotor vigilance (p < 0.001), working memory (p < 0.01), delayed word recall (p < 0.05), and subjective sleepiness (p < 0.01) at the first emergent awakening. At terminal awakening, neither cognitive performance nor subjective sleepiness was impaired after ingestion of zaleplon or zolpidem (5 mg and 10 mg) compared with placebo. CONCLUSIONS: Presleep ingestion of sleep medications, especially 10 mg zolpidem, poses a risk for performance errors after emergent awakenings near the expected PK,max. REGISTRATION: Optimize Astronaut Sleep Medication Efficacy and Individual Effects (clinicaltrials.gov ID NCT03526575).

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INTRODUCTION: The measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is the Medical Assessment Test used at the NASA Johnson Space Center to evaluate whether prolonged exposure to spaceflight increases the risk for premature osteoporosis in International Space Station (ISS) astronauts. The DXA scans of crewmembers' BMD during the first decade of the ISS existence showed precipitous declines in BMD for the hip and spine after the typical 6-mo missions. However, a concern exists that skeletal integrity cannot be sufficiently assessed solely by DXA measurement of BMD. Consequently, use of relatively new research technologies is being proposed to NASA for risk surveillance and to enhance long-term management of skeletal health in long-duration astronauts. Sibonga JD, Spector ER, Johnston SL, Tarver WJ. Evaluating bone loss in ISS astronauts.

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INTRODUCTION: U.S. astronauts undergo extensive job-related screening and medical examinations prior to selection in order to identify candidates optimally suited for careers in spaceflight. Screening medical standards evolved over many years and after extensive spaceflight experience. These standards assess health-related risks for each astronaut candidate, minimizing the potential for medical impact on future mission success. This document discusses the evolution of the Shuttle-era medical selection standards and the most common reasons for medical dis-qualification of applicants. METHODS: Data for astronaut candidate finalists were compiled from medical records and NASA archives from the period of 1978 to 2004 and were retrospectively reviewed for medically disqualifying conditions. RESULTS: During Shuttle selection cycles, a total of 372 applicants were disqualified due to 425 medical concerns. The most common disqualifying conditions included visual, cardiovascular, psychiatric, and behavioral disorders. During this time period, three major expert panel reviews resulted in refinements and alterations to selection standards for future cycles. DISCUSSION: Shuttle-era screening, testing, and specialist evaluations evolved through periodic expert reviews, evidence-based medicine, and astronaut medical care experience. The Shuttle medical program contributed to the development and implementation of NASA and international standards, longitudinal data collection, improved medical care, and occupational surveillance models. The lessons learned from the Shuttle program serve as the basis for medical selection for the ISS, exploration-class missions, and for those expected to participate in commercial spaceflight.

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UNLABELLED: This report documents the effects of photorefractive keratectomy (PRK) in an astronaut during a 12-day Russian Soyuz mission to the International Space Station in 2008. Changing environmental conditions of launch, microgravity exposure, and reentry create an extremely dynamic ocular environment. Although many normal eyes have repeatedly been subject to such stresses, the effect on an eye with a relatively thin cornea as a result of PRK has not been reported. This report suggests that PRK is a safe, effective, and well-tolerated procedure in astronauts during space flight. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

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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.

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Future long-duration spaceflights are now being planned to the Moon and Mars as a part of the "Vision for Space Exploration" program initiated by NASA in 2004. This report describes the design reference missions for the International Space Station, Lunar Base, and eventually a Mars Expedition. There is a need to develop more stringent preflight medical screening for crewmembers to minimize risk factors for diseases which cannot be effectively treated in flight. Since funding for space life sciences research and development has been eliminated to fund program development, these missions will be enabled by countermeasures much like those currently in use aboard the International Space Station. Artificial gravity using centrifugation in a rotating spacecraft has been suggested repeatedly as a "universal countermeasure" against deconditioning in microgravity and could be an option if other countermeasures are found to be ineffective. However, the greatest medical unknown in interplanetary flight may be the effects of radiation exposure. In addition, a Mars expedition would lead to a far greater level of isolation and psychological stress than any space mission attempted previously; because of this, psychiatric decompensation remains a risk. Historically, mortality and morbidity related to illness and injury have accounted for more failures and delays in new exploration than have defective transportation systems. The medical care system on a future Mars expedition will need to be autonomous and self-sufficient due to the extremely long separation from definitive medical care. This capability could be expanded by the presence of a physician in the crew and including simple, low-technology surgical capability.

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INTRODUCTION: The medical community of the International Space Station (ISS) has developed joint medical standards and evaluation requirements for Space Flight Participants ("space tourists") which are used by the ISS medical certification board to determine medical eligibility of individuals other than professional astronauts (cosmonauts) for short-duration space flight to the ISS. These individuals are generally fare-paying passengers without operational responsibilities. MATERIAL AND CONTEXT: By means of this publication, the medical standards and evaluation requirements for the ISS Space Flight Participants are offered to the aerospace medicine and commercial spaceflight communities for reference purposes. It is emphasized that the criteria applied to the ISS spaceflight participant candidates are substantially less stringent than those for professional astronauts and/or crewmembers of visiting and long-duration missions to the ISS. CONCLUSIONS: These medical standards are released by the government space agencies to facilitate the development of robust medical screening and medical risk assessment approaches in the context of the evolving commercial human spaceflight industry.

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Manned spaceflight is inherently risky and results in unique problems from a trauma and medical perspective. Emergency care under these special physiologic and environmental conditions calls for novel techniques for diagnosis and therapy.

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INTRODUCTION: The International Space Station will need to be as capable as possible in providing Advanced Cardiac Life Support (ACLS) and cardiopulmonary resuscitation (CPR). Previous studies with manikins in parabolic microgravity (0 G) have shown that delivering CPR in microgravity is difficult. End tidal carbon dioxide (PetCO2) has been previously shown to be an effective non-invasive tool for estimating cardiac output during cardiopulmonary resuscitation. Animal models have shown that this diagnostic adjunct can be used as a predictor of survival when PetCO2 values are maintained above 25% of pre-arrest values. METHODS: Eleven anesthetized Yorkshire swine were flown in microgravity during parabolic flight. Physiologic parameters, including PetCO2, were monitored. Standard ACLS protocols were used to resuscitate these models after chemical induction of cardiac arrest. Chest compressions were administered using conventional body positioning with waist restraint and unconventional vertical-inverted body positioning. RESULTS: PetCO2 values were maintained above 25% of both 1-G and O-G pre-arrest values in the microgravity environment (33% +/- 3 and 41 +/- 3). No significant difference between 1-G CPR and O-G CPR was found in these animal models. Effective CPR was delivered in both body positions although conventional body positioning was found to be quickly fatiguing as compared with the vertical-inverted. CONCLUSIONS: Cardiopulmonary resuscitation can be effectively administered in microgravity (0 G). Validation of this model has demonstrated that PetCO2 levels were maintained above a level previously reported to be predictive of survival. The unconventional vertical-inverted position provided effective CPR and was less fatiguing as compared with the conventional body position with waist restraints.

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BACKGROUND: Medical operations on the International Space Station will emphasize the stabilization and transport of critically injured personnel and so will need to be capable of advanced trauma life support (ATLS). METHODS: We evaluated the ATLS invasive procedures in the microgravity environment of parabolic flight using a porcine animal model. Included in the procedures evaluated were artificial ventilation, intravenous infusion, laceration closure, tracheostomy, Foley catheter drainage, chest tube insertion, peritoneal lavage, and the use of telemedicine methods for procedural direction. RESULTS: Artificial ventilation was performed and appeared to be unaltered from the 1-G environment. Intravenous infusion, laceration closure, percutaneous dilational tracheostomy, and Foley catheter drainage were achieved without difficulty. Chest tube insertion and drainage were performed with no more difficulty than in the 1-G environment due to the ability to restrain patient, operator and supplies. A Heimlich valve and Sorenson drainage system were both used to provide for chest tube drainage collection with minimal equipment, without the risk of atmospheric contamination, and with the capability to auto-transfuse blood drained from a hemothorax. The use of telemedicine in chest tube insertion was demonstrated to be useful and feasible. Peritoneal lavage using a percutaneous technique, although requiring less training to perform, was found to be dangerous in weightlessness due to the additional pressure of the bowel on the anterior abdominal wall creating a high risk of bowel perforation. CONCLUSIONS: The performance of ATLS procedures in microgravity appears to be feasible with the exception of diagnostic peritoneal lavage. Minor modifications to equipment and techniques are required in microgravity to effect surgical drainage in the presence of altered fluid dynamics, to prevent atmospheric contamination, and to provide for the restraint requirements. A parabolic simulation system was developed for equipment and procedure verification, physiological research, and possible crew medical officer training in the future.

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