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Orthostatic Hypotension After Long-Duration Space Flight: NASA's Experiences from the International Space Station

Our laboratory previously reported that the incidence of orthostatic hypotension (OH) was greater after long- than short-duration spaceflight in astronauts who participated in Mir Space Station and Space Shuttle missions. To confirm and extend these findings, we retrospectively examined tilt test data from International Space Station (ISS) and Shuttle astronauts. We anticipated that the proportion of ISS astronauts experiencing OH would be high on landing day and the number of days to recover greater after long- than short-duration missions. Methods: Twenty ISS and 66 Shuttle astronauts participated in 10-min 80? head-up tilt tests 10 d before launch (L-10), on landing day (R+0) or 1 d after landing (R+1). Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. Many astronauts repeated the test 3 d (R+3) after landing. Fisher?s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the tilt test on R+0. Cox regression was used to identify cardiovascular parameters that were associated with test completion across all tests, and mixed model analysis was used to compare the change and recovery rates between ISS and Shuttle astronauts. In these analyses, ISS data from R+0 and R+1 were pooled to provide sufficient statistical power. Results: The proportion of astronauts who completed the tilt test on R+0 without OH was less in ISS than in Shuttle astronauts (p=0.03). On R+0, only 2 of 6 ISS astronauts completed the test compared to 53 of 66 (80%) Shuttle astronauts. However, 8 of 9 ISS astronauts completed the test on R+1. On R+3, 13 of 15 (87%) of the ISS and 19 of 19 (100%) of the Shuttle astronauts completed the 10-min test. An index comprised of stroke volume and diastolic blood pressure provided a very good prediction of overall tilt survival. This index was altered by spaceflight similarly for both groups soon after landing (pooled R+0 and R+ 1), but ISS astronauts did not recover at the same rate as Shuttle astronauts (p=0.007). Conclusions: The proportion of ISS astronauts who could not complete the tilt test on R+0 due to OH (4 of 6) is similar to that reported in astronauts who flew on Mir (5 of 6). Further, cardiovascular parameters most closely associated with OH recover more slowly after long- compared to short-duration spaceflight.

Lee, Stuart M. C.↗

Long-Term Health Risk Quantification

Astronauts face hazards during spaceflight, including space radiation exposure, isolation and confinement, traveling far distances from Earth, reduced gravity levels, and closed and hostile environments. These hazards drive the definition of human health and performance risks associated with spaceflight. NASA’s Human System Risk Board maintains the human spaceflight risk posture for in-mission risks, as well as post-flight, Long-Term Health (LTH)risks potentially occurring later in the astronaut’s life. LTH risk encompasses the timeframe from immediately post-flight, through the rest of an astronaut’s career, through retirement, and until death. Possible LTH risk outcomes include the time and interventions needed for the astronaut to return to preflight physiological states after experiencing spaceflight hazards and recovery from any in-mission medical events that persist into the post-flight timeframe. It includes chronic complications that may arise due to experiencing in-flight medical conditions or injuries and medical conditions that occur later in life with a higher probability of occurrence or with more severity because of their spaceflight exposure. Finally, LTH risk outcomes can also include a reduction in life expectancy due to spaceflight exposures. There have been 144 medical conditions identified by NASA’s Lifetime Surveillance of Astronaut Health team to be associated with LTH risk. Epidemiological studies have been performed for some of these conditions to determine if astronauts suffer from an increased prevalence or severity of the condition due to their spaceflight experience compared to a comparable cohort .Differences in astronaut mortality or morbidity due to spaceflight experience were not detected in several of these studies. There were two cases where a modest increase in the incidence rate of astronaut LTH outcomes was detected. The first suggested an increase in the incidence of melanoma cases in astronauts, where the number of cases in astronauts were similar to the elevated number of cases observed in airplane pilots. The second provided some evidence of elevated numbers of cardiovascular disease events in astronauts compared to an appropriate healthy comparator cohort, which may warrant additional investigation. The lack of detection of LTH risk outcomes should not ease concerns about astronaut LTH. The studies highlighted here constitute only a small portion of the potential LTH conditions that could occur. Once epidemiological studies are performed on all conditions, significant findings may be detected. The analysis of astronaut LTH also suffers from limited numbers of data points because of the limited numbers of astronauts overall and the even fewer who have reached an age where LTH outcomes may begin to manifest. As shuttle and ISS astronauts begin to age and increase the feasibility of analysis, LTH outcomes may be detected. An application of risk quantification is the use of risk metrics within trade studies for resource prioritization and decision making. Trade studies regarding countermeasures to LTH risk outcomes would benefit from a quantification of LTH risk. NASA has ground-based processes in place such as astronaut screening and access to continuous medical monitoring and care during and after their astronaut career which are the main methods for mitigating LTH risk. In-mission countermeasures, such as acceptable levels of medical care and available countermeasures to counter spaceflight related physiological decrements, can mitigate a poor health and performance status immediately post-flight. Identifying appropriate risk metrics, obtaining valid quantities for them, and tying them to LTH countermeasures are necessary steps for realizing their use in trade studies. This presentation will highlight the challenges associated with the identification, quantification, and utilization of LTH risk metrics

Beth Lewandowski↗

Spheres of Earth: An Introduction to Making Observations of Earth Using an Earth System's Science Approach. Student Guide

Scientists from the Image Science and Analysis Laboratory (ISAL) at NASA's Johnson Space Center (JSC) work with astronauts onboard the International Space Station (ISS) who take images of Earth. Astronaut photographs, sometimes referred to as Crew Earth Observations, are taken using hand-held digital cameras onboard the ISS. These digital images allow scientists to study our Earth from the unique perspective of space. Astronauts have taken images of Earth since the 1960s. There is a database of over 900,000 astronaut photographs available at http://eol.jsc.nasa.gov . Images are requested by ISAL scientists at JSC and astronauts in space personally frame and acquire them from the Destiny Laboratory or other windows in the ISS. By having astronauts take images, they can specifically frame them according to a given request and need. For example, they can choose to use different lenses to vary the amount of area (field of view) an image will cover. Images can be taken at different times of the day which allows different lighting conditions to bring out or highlight certain features. The viewing angle at which an image is acquired can also be varied to show the same area from different perspectives. Pointing the camera straight down gives you a nadir shot. Pointing the camera at an angle to get a view across an area would be considered an oblique shot. Being able to change these variables makes astronaut photographs a unique and useful data set. Astronaut photographs are taken from the ISS from altitudes of 300 - 400 km (~185 to 250 miles). One of the current cameras being used, the Nikon D3X digital camera, can take images using a 50, 100, 250, 400 or 800mm lens. These different lenses allow for a wider or narrower field of view. The higher the focal length (800mm for example) the narrower the field of view (less area will be covered). Higher focal lengths also show greater detail of the area on the surface being imaged. Scientists from the Image Science and Analysis Laboratory (ISAL) at NASA s Johnson Space Center (JSC) work with astronauts onboard the International Space Station (ISS) who take images of Earth. Astronaut photographs, sometimes referred to as Crew Earth Observations, are taken using hand-held digital cameras onboard the ISS. These digital images allow scientists to study our Earth from the unique perspective of space. Astronauts have taken images of Earth since the 1960s. There is a database of over 900,000 astronaut photographs available at http://eol.jsc.nasa.gov . Images are requested by ISAL scientists at JSC and astronauts in space personally frame and acquire them from the Destiny Laboratory or other windows in the ISS. By having astronauts take images, they can specifically frame them according to a given request and need. For example, they can choose to use different lenses to vary the amount of area (field of view) an image will cover. Images can be taken at different times of the day which allows different lighting conditions to bring out or highlight certain features. The viewing angle at which an image is acquired can also be varied to show the same area from different perspectives. Pointing the camera straight down gives you a nadir shot. Pointing the camera at an angle to get a view across an area would be considered an oblique shot. Being able to change these variables makes astronaut photographs a unique and useful data set. Astronaut photographs are taken from the ISS from altitudes of 300 - 400 km (approx.185 to 250 miles). One of the current cameras being used, the Nikon D3X digital camera, can take images using a 50, 100, 250, 400 or 800mm lens. These different lenses allow for a wider or narrower field of view. The higher the focal length (800mm for example) the narrower the field of view (less area will be covered). Higher focal lengths also show greater detail of the area on the surface being imaged. There are four major systems or spheres of Earth. They are: Atmosphere, Biosphere, Hydrosphe, and Litho/Geosphere.

Graff, Paige Valderrama↗

Career Excess Mortality Risk from Diagnostic Radiological Exams Required for Crewmembers Participating in Long Duration Space Flight

NASA requires astronauts to undergo diagnostic x-ray examinations as a condition for their employment. The purpose of these procedures is to assess the astronaut s overall health and to diagnose conditions that could jeopardize the success of long duration space missions. These include exams for acceptance into the astronaut corps, routine periodic exams, as well as evaluations taken pre and post missions. Issues: According to NASA policy these medical examinations are considered occupational radiological exposures, and thus, are included when computing the astronaut s overall radiation dose and associated excess cancer mortality risk. As such, astronauts and administrators are concerned about the amount of radiation received from these procedures due to the possibility that these additional doses may cause astronauts to exceed NASA s administrative limits, thus disqualifying them from future flights. Methods: Radiation doses and cancer mortality risks following required medical radiation exposures are presented herein for representative male and female astronaut careers. Calculation of the excess cancer mortality risk was performed by adapting NASA s operational risk assessment model. Averages for astronaut height, weight, number of space missions and age at selection into the astronaut corps were used as inputs to the NASA risk model. Conclusion: The results show that the level of excess cancer mortality imposed by all required medical procedures over an entire astronaut s career is approximately the same as that resulting from a single short duration space flight (i.e. space shuttle mission). In short the summation of all medical procedures involving ionizing radiation should have no impact on the number of missions an astronaut can fly over their career. Learning Objectives: 1. The types of diagnostic medical exams which astronauts are subjected to will be presented. 2. The level of radiation dose and excess mortality risk to the average male and female astronaut will be presented.

Dodge, C. W.↗

Effects of Long Duration Spaceflight on Venous and Arterial Compliance

The visual impairment and intracranial pressure syndrome (VIIP) is a newly described space flight-associated medical condition made up of a constellation of symptoms affecting at least 34% of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures, and is thought to be related to elevated intracranial pressure secondary to space flightinduced cephalad fluid shifts. Loss of visual acuity could be a significant threat to crew health and performance and may be suggestive of other adaptations with implications for years post-flight. Our primary objective is to determine whether vascular compliance is altered by space flight and whether such adaptations are related to the incidence of VIIP. In particular, we will measure ocular parameters and vascular compliance in vessels of the head and neck in astronauts who have no space flight experience, in astronauts before, during, and after space flight, and in bed rest subjects with conditions similar to space flight. Additionally, we will analyze astronaut data from the Lifetime Surveillance of Astronaut Health (LSAH) archive to determine which factors might be predictive of the development of VIIP. The project will be conducted in four separate but related parts. To understand the baseline condition of astronauts without any prior space flight experience, we will study 10 astronauts who have never flown in space by performing a comprehensive evaluation of the vasculature of the head, neck and eyes. Hemodynamic data (stroke volume and blood pressure), ocular (tonometry and ocular ultrasound), venous and arterial parameters will be acquired across a range of tilt angles (20, 10, 0, -10, -20 degrees). Vessels to be studied include the temporal, jugular, and vertebral veins and the cerebral, carotid and vertebral arteries. Ophthalmic data from the annual physical will be obtained through data sharing. To examine the relation between vascular compliance in the head and neck and the development of VIIP after a long duration space flight, we will study 10 astronauts before, during, and after long-duration ISS missions. Pre- and post-flight testing will be identical to that described above. During flight, images of the same vessels of interest will be obtained for later analysis. Ophthalmic data including VIIP scores will be obtained through data sharing from medically-required tests. To investigate the effects of age and elevated sodium intake, two potential contributors to VIIP, we will study 24 men (in two age groups: 25-35 and 45-55) during a 14 day 6deg head-down bed rest, a well-accepted analog of space flight. Standard NASA bed rest conditions will be maintained except for dietary sodium. Sodium intake will be similar to that of ISS astronauts, which is higher than consumed in previous bed rest studies. Pre- and post-bed rest testing procedures will be identical to the testing protocol described above for astronauts. Ophthalmic testing (optical coherence tomography, fundoscopy, and tonometry) will be conducted on the same day that vascular compliance measures are obtained. To identify parameters that may relate to an increase in an astronaut's susceptibility to developing VIIP, we will use data mining techniques to evaluate astronaut data obtained from the LSAH. Medical history, family history, space flight history and its related exposures, and history of high performance jet aircraft exposure will be examined for their potential relationship to ocular data. We hypothesize that the cephalad fluid shift induced by space flight will result in structural and functional adaptations in head and neck vessels leading to decreased vascular compliance and related to the development of VIIP symptoms. Further, although VIIP has not been observed in previous bed rest studies, we hypothesize that an elevated sodium intake will increase the incidence of VIIP symptoms in this space flight analog. Finally, we hypothesize that data mining analyses will reveal relationships between health history, previous exposures (including space flight and high performance aircraft), and the development of VIIP in the astronaut population.

Ribeiro, L. C.↗

Effects of Long Duration Spaceflight on Venous and Arterial Compliance in Astronants

1. Project Overview Visual impairment and intracranial pressure (VIIP) is a spaceflight-associated medical condition affecting at least a third of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures. In some astronauts, eye-related changes do not revert back to the preflight state upon return to Earth. Our team will study some of the possible causes for this syndrome. This will be achieved by reviewing previous astronaut data for factors that may predispose astronauts to higher rates of developing this syndrome or greater severity of symptoms. Additionally, we will conduct 3 separate experiments that will characterize vessels in the head and neck and measure the effects of the experimental conditions on ocular structures and function. 2. Technical Summary The primary objective of this study is to determine whether vascular compliance is altered by spaceflight and whether such adaptations are related to the incidence of the VIIP. In particular, we will measure ocular parameters and vascular compliance in vessels of the head and neck in astronauts who have no spaceflight experience (Ground), in astronauts before, during, and after spaceflight (Flight), and in bed rest subjects with conditions similar to spaceflight (Bed Rest). Additionally, we will analyze astronaut data from the Lifetime Surveillance of Astronaut Health (LSAH) archives to determine which factors might be predictive of the development of VIIP (Data Mining). The project will be conducted in four separate, but related parts. Hypothesis The central hypothesis of this proposal is that exposure to the spaceflight environment aboard the ISS may lead to development of the VIIP syndrome (increased intracranial pressure and impaired visual acuity) and that this may be related to alterations in venous and/or arterial compliance in the head and neck. Specific Aims 1. To determine whether noninvasive measures of venous and arterial compliance are altered by long-duration spaceflight exposure in ISS astronauts and whether these changes are related to the development of the VIIP syndrome. (Flight) 2. To determine whether previous spaceflight experience predispose astronauts to lower venous compliance and/or the development of the VIIP syndrome. (Ground + Flight) 3. To use a 14-day, 6deg head-down-tilt bed rest as a model of spaceflight, to evaluate the effect of aging on vascular compliance using a subject population similar to younger (25-35 yr) and older (45-55 yr) astronaut cohorts. (Bed Rest) 4. To determine what factors contribute to lower venous compliance and/or the development of the VIIP syndrome in astronauts. (Data Mining) 3. Earth Applications This research may inform the mechanisms that regulate blood/fluid flow in and out of the brain in the head and neck. This information may help with understanding of the mechanisms behind idiopathic intracranial hypertension. 4. Link to NASA Taskbook Entry Not Yet Available

Platts, Steven↗

Space Flight-Induced Intracranial Hypertension: An Ophthalmic Review

Background: Although physiologic and pathologic changes associated with microgravity exposure have been studied extensively, the effect of this environment on the eye is largely unknown. Over the last several years, NASA s Space Medicine Division has documented astronauts presenting with varying degrees of disc edema, globe flattening, choroidal folds, cotton wool spots, and hyperopic shifts after long-duration space flight. Methods: Before and after long-duration space flight, six astronauts underwent complete eye examinations to include cycloplegic and/or manifest refraction and fundus photography. Five of these astronauts had Optical Coherence Tomography (OCT) and Magnetic Resonance Imaging (MRI) performed following their missions. Results: Following exposure to space flight of approximately 6-months duration, six astronauts had neuro-ophthalmic findings. These consisted of disc edema in four astronauts, globe flattening in four astronauts, choroidal folds in four astronauts, cotton wool spots in three astronauts, nerve fiber layer thickening by OCT in five astronauts, and decreased near vision in five astronauts. Four of the astronauts with near vision complaints had a hyperopic shift equal to or greater than + 0.50D between pre- and post-mission spherical equivalent refraction in one or both eyes (range +0.50D to +1.50D). These same four had globe flattening by MRI. Conclusions: The findings we describe may have resulted from a rise in intracranial pressure caused by microgravity fluid shifts, and could represent parts of a spectrum of ocular and cerebral responses to extended microgravity.

Gibson, Charles Robert↗

Evaluation of an Anthropometric Human Body Model for Simulated EVA Task Assessment

One of the more mission-critical tasks performed in space is extravehicular activity (EVA) which requires the astronaut to be external to the station or spacecraft, and subsequently at risk from the many threats posed by space. These threats include, but are not limited to: no significant atmosphere, harmful electromagnetic radiation, micrometeoroids, and space debris. To protect the astronaut from this environment, a special EVA suit is worn which is designed to maintain a sustainable atmosphere (at 1/3 atmosphere) and provide protection against the hazards of space. While the EVA suit serves these functions well, it does impose limitations on the astronaut as a consequence of the safety it provides. Since the astronaut is in a virtual vacuum, any atmospheric pressure inside the suit serves to pressurize the suit and restricts mobility of flexible joints (such as fabric). Although some of the EVA suit joints are fixed, rotary-style joints, most of the mobility is achieved by the simple flexibility of the fabric. There are multiple layers of fabric, each of which serves a special purpose in the safety of the astronaut. These multiple layers add to the restriction of motion the astronaut experiences in the space environment. Ground-based testing is implemented to evaluate the capability of EVA-suited astronauts to perform the various tasks in space. In addition to the restriction of motion imposed by the EVA suit, most EVA activity is performed in a micro-gravity (weight less) environment. To simulate weightlessness EVA-suited testing is performed in a neutral buoyancy simulator (NBS). The NBS is composed of a large container of water (pool) in which a weightless environment can be simulated. A subject is normally buoyant in the pressurized suit; however he/she can be made neutrally buoyant with the addition of weights. In addition, most objects the astronaut must interface with in the NBS sink in water and flotation must be added to render them "weightless". The implementation of NBS testing has proven to invaluable in the assessment of EVA activities performed with the Orbiter and is considered to be a key step in the construction of the International Space Station (ISS). While the NBS testing is extremely valuable, it does require considerable overhead to maintain and operate. It has been estimated that the cost of utilizing the facility is approximately $10,000 per day. Therefore it is important to maximize the utility of NBS testing for optimal results. One important aspect to consider in any human/worksite interface is the considerable wealth of anthropometric and ergonomic data available. A subset of this information specific to EVA activity is available in NASA standard 3000. The difficulty in implementing this data is that most of the anthropometric information is represented in a two-dimensional format. This poses some limitations in complete evaluation of the astronaut's capabilities in a three-dimensional environment. Advances in computer hardware and software have provided for three-dimensional design and implementation of hardware with the advance of computer aided design (CAD) software. There are a number of CAD products available and most companies and agencies have adopted CAD as a fundamental aspect of the design process. Another factor which supports the use of CAD is the implementation of computer aided manufacturing (CAM) software and hardware which provides for rapid prototyping and decreases the time to product in the design process. It is probable that most hardware to be accessed by astronauts in EVA or IVA (intravehicular activity) has been designed by a CAD system, and is therefore represented in three-dimensional space for evaluation. Because of the implementation of CAD systems and the movement towards early prototyping, a need has arisen in industry and government for tools which facilitate the evaluation of ergonomic consideration in a three-dimensional environment where the hardware has been designed by the CAD tools. One such product is Jack which was developed by the University of Pennsylvania with funding from several government agencies, including NASA. While the primary purpose of Jack is to model human figures in a ground-based (gravity) environment, it can be utilized to evaluate EVA-suited activities as well. The effects of simulated gravity must be turned off by turning off "behaviors". Although Jack provides human figures for manipulation, the primary instrument to be evaluated for EVA mobility is the work envelope provided by the EVA suit. An EVA Jack suit model has been developed by NASA-JSC and was utilized in this study. This suit model provided a more restrictive motion environment as expected for an EVA suited subject. As part of this study, the anthropometric dimensions for a 50th percentile male were compared with basic anthropometric data and were found to be representative for the population group expected in the NASA flight program. The joints for the suit were created in a manner which provided consistent performance with EVA reach envelopes published in NASA standard #3000.

Etter, Brad↗

Post-Flight Back Pain Following International Space Station Missions: Evaluation of Spaceflight Risk Factors

INTRODUCTION Back pain during spaceflight has often been attributed to the lengthening of the spinal column due to the absence of gravity during both short and long-duration missions. Upon landing and re-adaptation to gravity, the spinal column reverts back to its original length thereby causing some individuals to experience pain and muscular spasms, while others experience no ill effects. With International Space Station (ISS) missions, cases of back pain and injury are more common post-flight, but little is known about the potential risk factors. Thus, the purpose of this project was to perform an initial evaluation of reported post-flight back pain and injury cases to relevant spaceflight risk factors in United States astronauts that have completed an ISS mission. METHODS All US astronauts who completed an ISS mission between Expeditions (EXP) 1 and 41 (2000-2015) were included in this evaluation. Forty-five astronauts (36 males and 9 females) completed 50 ISS missions during the study time period, as 5 astronauts completed 2 ISS missions. Researchers queried medical records of the 45 astronauts for occurrences of back pain and injury. A case was defined as any reported event of back pain or injury to the cervical, thoracic, lumbar, sacral, or coccyx spine regions. Data sources for the cases included the Flight Medicine Clinic's electronic medical record; Astronaut Strength, Conditioning and Rehabilitation electronic documentation; the Private Medical Conference tool; and the Space Medicine Operations Team records. Post-flight cases were classified as an early case if reported within 45 days of landing (R + 45) or a late case if reported from R + 46 to R + 365 days after landing (R + 1y). Risk factors in the astronaut population for back pain include age, sex, prior military service, and prior history of back pain. Additionally, spaceflight specific risk factors such as type of landing vehicle and onboard exercise countermeasures were included to evaluate their contribution to post-flight cases. Prior history of back pain included back pain recorded in the medical record within 3 years prior to launch. Landing vehicle was included in the model to discern if more astronauts experienced back pain or injury following a Shuttle or Soyuz landing. Onboard exercise countermeasures were noted for those astronauts who had a mission following 2009 deployment of the Advanced Resistive Exercise Device (aRED) (EXP 19 to 41). T-test and chi-squared tests were performed to evaluate the association between each individual risk factor and post-flight case. Logistic regression was used to evaluate the combined contribution of all the risk factors on post-flight cases. Separate models were calculated for cases reported by R + 45 and R + 1y. RESULTS During the study time period, there were 13 post-flight cases reported by R + 45 and an additional 5 reported by R + 1y. Most of these cases have been reported since EXP 19 with 10 cases by R + 45 and 4 by R + 1y. Individual risk factors of age, sex, landing vehicle, and prior military service were not significantly associated with post-flight cases identified at R + 45 or R + 1y (p greater than 0.05). Having back pain or injury within 3 years prior to launch significantly increased the likelihood of becoming a case by R + 1y (p = 0.041), but not at R+45 (p=0.204). Additionally, astronauts who experienced onboard exercise countermeasures that included aRED had a significantly increased risk of becoming a case at R + 45 (p = 0.024) and R + 1y (p=0.003). Multiple logistic regression evaluating all the risk factors for cases identified no significant risk factors at either the R + 45 or R + 1y time period (p greater than 0.05). Overall model fit was poor for both the R + 45 (R(exp 2) = 0.132) and R + 1y (R(exp 2) = 0.186) cases showing that there are risk factors not represented in our model. CONCLUSIONS Regardless of cause, post-flight cases are reported more often since aRED was deployed in 2009. This may reflect improved documentation or unidentified risk factors. No spaceflight risk factor explains the data fully. Post-flight cases are probably due to multi-faceted factors that are not easily elucidated in the medical data.

Laughlin, M. S.↗

Risk of Bone Fracture due to Spaceflight-induced Changes to Bone

The Human Research Program (HRP) is taking a biomechanical approach to assessing subsequent fracture risk in active astronauts as a consequence of spaceflight exposure. Triennial testing of active and retired astronauts continues as Space Medicine monitors for a premature diagnosis of primary osteoporosis, which is associated with age-related bone loss and skeletal fragility. This updated 2023 Fracture Evidence Report has expanded the description of skeletal changes to capture the full effects of spaceflight on bone: • Recent analysis of fractures from health records of the full astronaut cohort, suggests an increased incidence rate of hip and spine fractures in astronauts following longer spaceflight duration flights compared to incident rates found in shorter duration flights. • Routine preflight-to-postflight surveillance by DXA (dual-energy x-ray absorptiometry) does not provide the full detection of loss and recovery in the long-duration (LD) astronaut nor the full recovery of hip trabecular bone. • The inclusion of hip quantitative computed tomography (QCT) in flight studies delineates effects of spaceflight, of countermeasures, and of post-flight recovery on cortical and trabecular bone parameters—some of which are verified predictors of hip fracture in the aged. • QCT detects and compares the distinct countermeasure effects of the pharmaceutical alendronate and of resistive exercise (on the Advanced Resistive Exercise Device, ARED) in specific cortical and trabecular bone sub-regions during spaceflight. • A published comparison of QCT-determined loss rates of hip trabecular bone in LD astronauts compared to terrestrial cohorts suggest that accelerated loss rates in trabecular volumetric BMD (vBMD) during spaceflight might be analogous to skeletal effects of accelerated loss rates in females due to menopause, potentially leading to disruptions in trabecular microarchitecture. • A dataset of finite element (FE) estimates of hip bone strength in aging terrestrial cohorts (spanning astronaut age-range) provides comparative context for changes in the FE of hip bone strength in LD astronauts, including comparison (force unit of newton) to percentiles (50th, 75th, and 100th) of sex-matched aged humans with hip fractures. • Risk of fracture, due to the mechanical overloading of bones, is being updated with IMPACT, the next-generation tool suite for probabilistic risk assessment (PRA) for exploration missions being created by the Exploration and Medical Capability Element (ExMC) at NASA. IMPACT is currently in development and will not be included in this 2024 update. The risk for fracture necessitates understanding the relationship between applied loads to bone and the biomechanical competence of bone. The Risk for Early Onset Osteoporosis focuses on the weakened condition of bone (including development of new technologies, measurements of novel skeletal attributes, translation of multiple measures to an index of bone fragility, and interpretations of data used to reflect a weakened bone), while the Risk for Fracture assesses factors that influence the probability an astronaut would encounter applied loads exceeding the biomechanical competence of bones, resulting in fracture. This Evidence Report combines the research gaps and tasks associated with both risks.

Fracture↗

Microgravity Investigation of Crew Reactions in 0-G (MICRO-G)

There is a need for a human factors, technology-based bioastronautics research effort to develop an integrated system that reduces risk and provides scientific knowledge of astronaut-induced loads and motions during long-duration missions on the International Space Station (ISS), which will lead to appropriate countermeasures. The primary objectives of the Microgravity Investigation of Crew Reactions in 0-G (MICRO-GI research effort are to quantify astronaut adaptation and movement as well as to model motor strategies for differing gravity environments. The overall goal of this research program is to improve astronaut performance and efficiency through the use of rigorous quantitative dynamic analysis, simulation and experimentation. The MICRO-G research effort provides a modular, kinetic and kinematic capability for the ISS. The collection and evaluation of kinematics (whole-body motion) and dynamics (reacting forces and torques) of astronauts within the ISS will allow for quantification of human motion and performance in weightlessness, gathering fundamental human factors information for design, scientific investigation in the field of dynamics and motor control, technological assessment of microgravity disturbances, and the design of miniaturized, real-time space systems. The proposed research effort builds on a strong foundation of successful microgravity experiments, namely, the EDLS (Enhanced Dynamics Load Sensors) flown aboard the Russian Mir space station (19961998) and the DLS (Dynamic Load Sensors) flown on Space Shuttle Mission STS-62. In addition, previously funded NASA ground-based research into sensor technology development and development of algorithms to produce three-dimensional (3-0) kinematics from video images have come to fruition and these efforts culminate in the proposed collaborative MICRO-G flight experiment. The required technology and hardware capitalize on previous sensor design, fabrication, and testing and can be flight qualified for a fraction of the cost of an initial spaceflight experiment. Four dynamic load sensors/restraints are envisioned for measurement of astronaut forces and torques. Two standard ISS video cameras record typical astronaut operations and prescribed IVA motions for 3-D kinematics. Forces and kinematics are combined for dynamic analysis of astronaut motion, exploiting the results of the detailed dynamic modeling effort for the quantitative verification of astronaut IVA performance, induced-loads, and adaptive control strategies for crewmember whole-body motion in microgravity. This comprehensive effort, provides an enhanced human factors approach based on physics-based modeling to identify adaptive performance during long-duration spaceflight, which is critically important for astronaut training as well as providing a spaceflight database to drive countermeasure design.

Newman, Dava↗

Latent Virus Reactivation: From Space to Earth

Reactivation of latent viruses is a recognized consequence of decreased immunity. More recently viral reactivation has been identified as an important in vivo indicator of clinically relevant immune changes. Viral reactivation can be determined quickly and easily by the presence of virus in saliva and other body fluids. Real-time polymerase chain reaction (PCR) is a highly sensitive and specific molecular method to detect the presence of specific viral DNA. Studies in astronauts demonstrated that herpes simplex virus type 1(HSV-1), Epstein-Barr Virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate at rates above normal during and after spaceflight in response to moderately decreased T-cell immunity. This technology was expanded to patients on Earth beginning with human immune deficiency virus (HIV) immuno-compromised patients. The HIV patients shed EBV in saliva at rates 9-fold higher than observed in astronauts demonstrating that the level of EBV shedding reflects the severity of impaired immunity. Whereas EBV reactivation is not expected to produce serious effects in astronauts on missions of 6 months or less, VZV reactivation in astronauts could produce shingles. Reactivation of live, infectious VZV in astronauts with no symptoms was demonstrated in astronauts during and after spaceflight. We applied our technology to study VZV-induced shingles in patients. In a study of 54 shingles patients, we showed salivary VZV was present in every patient on the day antiviral (acyclovir) treatment was initiated. Pain and skin lesions decreased with antiviral treatment. Corresponding decreases in levels of VZV were also observed and accompanied recovery. Although the level of VZV in shingles patients before the treatment was generally higher than those found in astronauts, lower range of VZV numbers in shingles patients overlapped with astronaut s levels. This suggests a potential risk of shingles to astronauts resulting from reactivation of VZV. In another clinical study of 25 shingles patients, PCR technology detected VZV in the serum and peripheral blood mononuclear cells of all 25 patients demonstrating for the first time that viremia is a common manifestation of herpes shingles.

Mehta, Satish K.↗

Validation of A Sensorimotor Disorientation Ground Analog

INTRODUCTION Simulating the sensorimotor disorientation effects of gravity transitions after prolonged stays in microgravity is exceedingly challenging on Earth. In a previous study [1], a Sensorimotor Disorientation Analog (SDA) was developed based on subjective feedback from previously flown astronauts. The purpose of this study was to validate this SDA by comparing performance in movement tasks that have a wealth of spaceflight data against task performance while using the SDA. METHODS Thirty healthy non-astronaut subjects (17 males, 13 females; Mean ± SD, Age: 33.5 ± 7.2 years, Height: 68.0 ± 3.4 in, Weight: 164 ± 26 lbs.) volunteered to participate in this study. Subjects performed three movement tasks: computerized dynamic posturography (CDP), obstacle walk, and tandem walk. For CDP, subjects maintained an upright stance for 20s with eyes closed on an unstable pitch sway-referenced platform with head erect (sensory organization test (SOT)-5) and with head pitch ±20° to an auditory cue(SOT-5M). The obstacle walk involved a sit-to-stand with 10s of quiet stance followed by walking to and around a cone placed 4m away while navigating a 30cm obstacle to the cone and back. The tandem walk involved walking heel-to-toe for approximately 10-12 steps with eyes open and eyes closed. Subjects performed the three movement tasks under three levels of the SDA replicating different time points of recovery: none (preflight), low (Return (R)+24- 48hours), and high (R+0- 24hours). The SDA included galvanic vestibular stimulation (GVS) to disorient the vestibular system and a weighted suit (trunk, wrists, and ankles) to alter proprioceptive feedback and replicate subjective heaviness. RESULTS As the SDA magnitude increased, overall performance outcomes decreased. However, the ability of the SDA to replicate the range of astronaut postflight performance was task dependent. CDP SOT-5 performance across SDA levels closely replicated astronaut performance at all time points. SOT-5M, however, had minimal performance changes across SDA levels and was unable to replicate astronaut performance. The obstacle walk showed performance changes across SDA levels and matched astronaut performance preflight and at R+24-48hrs (low). Obstacle walk performance at the high SDA level was reduced in comparison to the low level; however, it was not replicative of astronaut performance immediately after landing. Last, tandem walk had distinct groupings of performance across SDA levels and was able to elicit a high level of disorientation consistent with R+0-24 hours (high) postflight performance for eyes open and eyes closed. The low SDA level for both eyes open and eyes closed was more disruptive than previous crewmember performance at the R+24-48 hours timepoint. CONCLUSION The SDA was developed to replicate postflight sensorimotor disruptions. However, it is well-known that immediately post-landing, astronauts can experience motion sickness, dehydration, fatigue, orthostatic intolerance, illusory sensations, lumbar pain, etc. This multi-system response to return to 1G varies widely across astronauts and, as such, it was not unexpected that the extreme ends of responses in the R+0-24hrs time period were the most difficult to replicate. These results suggest that the SDA levels are able to elicit distinct performance groupings and, although not able to perfectly replicate R+0-24hrs, the SDA did replicate a large range of performance after return to Earth.

S C Moudy↗