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Clinical Core Competency Training for NASA Flight Surgeons

Introduction: The cohort of NASA flight surgeons (FS) is a very accomplished group with varied clinical backgrounds; however, the NASA Flight Surgeon Office has identified that the extremely demanding schedule of this cohort prevents many of these physicians from practicing clinical medicine on a regular basis. In an effort to improve clinical competency, the NASA FS Office has dedicated one day a week for the FS to receive clinical training. Each week, an FS is assigned to one of five clinical settings, one being medical patient simulation. The Medical Operations Support Team (MOST) was tasked to develop curricula using medical patient simulation that would meet the clinical and operational needs of the NASA FS Office. Methods: The MOST met with the Lead FS and Training Lead FS to identify those core competencies most important to the FS cohort. The MOST presented core competency standards from the American Colleges of Emergency Medicine and Internal Medicine as a basis for developing the training. Results: The MOST identified those clinical areas that could be best demonstrated and taught using medical patient simulation, in particular, using high fidelity human patient simulators. Curricula are currently being developed and additional classes will be implemented to instruct the FS cohort. The curricula will incorporate several environments for instruction, including lab-based and simulated microgravity-based environments. Discussion: The response from the NASA FS cohort to the initial introductory class has been positive. As a result of this effort, the MOST has identified three types of training to meet the clinical needs of the FS Office; clinical core competency training, individual clinical refresher training, and just-in-time training (specific for post-ISS Expedition landings). The MOST is continuing to work with the FS Office to augment the clinical training for the FS cohort, including the integration of Web-based learning.

Polk, J. D.↗

Smart Ultrasound Remote Guidance Experiment (SURGE)- Concept of Operations Evaluation for Using Remote Guidance Ultrasound for Planetary Space Flight

Introduction Use of remote guidance (RG) techniques aboard the International Space Station (ISS) has enabled astronauts to collect diagnostic-level ultrasound images. Exploration class missions will require this cohort of (typically) non-formally trained sonographers to operate with greater autonomy given the longer communication delays (2 seconds for ISS vs. >6 seconds for missions beyond the Moon) and communication blackouts. To determine the feasibility and training requirements for autonomous ultrasound image collection by non-expert ultrasound operators, ultrasound images were collected from a similar cohort using three different image collection protocols: RG only, RG with a computer-based learning tool (LT), and autonomous image collection with LT. The groups were assessed for both image quality and time to collect the images. Methods Subjects were randomized into three groups: RG only, RG with LT, and autonomous with LT. Each subject received 10 minutes of standardized training before the experiment. The subjects were tasked with making the following ultrasound assessments: 1) bone fracture and 2) focused assessment with sonography in trauma (FAST) to assess a patient s abdomen. Human factors-related questionnaire data were collected immediately after the assessments. Results The autonomous group did not out-perform the two groups that received RG. The mean time for the autonomous group to collect images was less than the RG groups, however the mean image quality for the autonomous group was less compared to both RG groups. Discussion Remote guidance continues to produce higher quality ultrasound images than autonomous ultrasound operation. This is likely due to near-instant feedback on image quality from the remote guider. Expansion in communication time delays, however, diminishes the capability to provide this feedback, thus requiring more autonomous ultrasound operation. The LT has the potential to be an excellent training and coaching component for autonomous ultrasound image collection during exploration missions.

Hurst, Victor, IV↗

RadBREAD: Radiation Biology Research at an Elevated Altitude through Dosimetry – A student-designed payload

NASA uses extreme environment platforms (ground testing facilities, high-altitude balloons and aircraft, and CubeSats) to provide greater understanding of the conditions and limitations of extra-terrestrial environments. As part of a two-week flight planned for summer 2021, RadBREAD (Radiation Biology Research at an Elevated Altitude through Dosimetry) will fly as a secondary payload consisting of a M-42C (German Aerospace Center, DLR) ionizing radiation dosimeter, UV micro-logger, and multiple desiccated yeast samples. The platform is a novel high-altitude solar-powered aircraft: the Swift Engineering High-Altitude samples. The platform is a novel high-altitude solar-powered aircraft: the Swift Engineering High-Altitude Long-Endurance Unmanned Aircraft System (HALE UAS), which offers significantly longer flight durations than other high-altitude platforms. The yeast Saccharomyces cerevisiae will provide meaningful biological correlation for the sensor readings, due to its resistance to extremely low temperature and pressure when desiccated, ease of genetic manipulation, and homology to human genes. The RadBREAD team comprises the 2020 cohort of NASA’s Space Life Sciences Training Program (SLSTP) research associates as well as NASA scientists, engineers and radiation experts from NASA and the DLR. Yeast survival, metabolic, and transcriptomic changes will be correlated with environmental data collected during long-term exposure to the upper atmosphere. Additionally, the team will evaluate the upper atmospheric environment (radiation, pressure, and temperature) provided by the HALE UAS platform as a Mars surface analog for biological payloads. We hypothesize that exposure to upper atmospheric conditions during the HALE UAS flight will alter the survival, metabolism, and transcriptome of desiccated wild-type S. cerevisiae upon rehydration compared to sensitive and tolerant yeast strains exposed to the same conditions, and between the flight samples compared to asynchronous ground controls.

radiation exposure↗

Manual Crew Override of Vehicle Landings Following G-Transitions

BACKGROUND Manual control during exploration spaceflight consists of both planned automated supervisory control and unplanned crew override. This crew override capability is critical to enable overall mission success during landing contingencies. However, the introduction of manual override capabilities must be implemented to enable crews to mitigate risks introduced by human error. Adaptive changes in the sensorimotor system can manifest during g-transitions as spatial disorientation. While training and landing aids enable successful landing through disorientation, these adaptive changes may increase cognitive demand that needs to be accounted for in the manual control strategy. It is important to characterize these effects as soon as possible following the G-transition to develop appropriate countermeasures. METHODS The following study seeks to inform the risk associated with altered sensorimotor and vestibular function impacting critical mission tasks. We aim to characterize the effects of short and long-duration weightlessness on manual control following G-transitions using simulated lunar landing on a six-degree-of-freedom (6DOF) motion base, a fixed base simulation, and a supervisory control tablet task. The primary goal is to understand the impact of spaceflight on crew ability to perform manual crew override and supervisory control. This aim will be assessed by comparing pre- versus postflight simulation performance in crewmembers assigned to either short duration (< 30 day) or long duration (~6- month) missions to the International Space Station (ISS). We hypothesize there will be postflight increases in the percent time that pilots are outside of the acceptable range for recommended vehicle state parameters and the reaction time for secondary cognitive tasks. Ground-based control subjects, who are demographically matched to the crew considering age (± 5 years) and gender, will undergo the same testing schedule as the crew to examine the effects of flight phase independent of microgravity exposure. The second aim is to examine how adaptive changes in vestibular and cognitive function relate to changes in manual crew override proficiency. Crew performance for a sensorimotor perceptual test battery will evaluate motion perception tracking, roll nulling, and/or vection sensitivity using the 6DOF motion base. We hypothesize that a higher severity of vestibular alterations will be associated with increased percent time outside of guidance limits. Motion sickness severity and sleepiness will also be evaluated. To determine the impact of “just-in-time” training, the third aim seeks to compare performance during on-board lunar landing tasks conducted late in-flight to early postflight. We hypothesize that proficiency on the “just-in-time” laptop trainer late in mission will be positively correlated with early postflight proficiency on the same task. The final aim will establish assessments of performance, training protocols, and the learning progression in a ground-control cohort of first-time users. RESULTS The assessment of the learning progression associated with the piloting task on the motion base system with thirty ground subjects will be reported. Learning curves will be established across four distinct sessions and within session considering trial difficulty. The difficulty of the landing task can be modulated with the landing divert distance and cross or downrange difficulty. Results may include changes in performance across multiple trials of a multi-attribute lunar tablet supervisory control task. Preliminary investigations of eighteen subjects who completed vestibular threshold and motion perception tasks offer expected performance ranges for upcoming preflight crew evaluations. The results yielded an average roll threshold of 0.46 ± 0.30 deg/s and an average roll nulling root mean square error performance of 2.52 ± 0.52 deg/s. RELEVANCE This project will deliver an operational demonstration of crew monitoring capability following spaceflight and identify potential deficits that may require remediation. Comparison of individual vestibular and cognitive changes with crew performance will help better characterize the manual control risks associated with sensorimotor alterations. Ground testing will evaluate learning progression, refine training protocols, and serve as a control cohort for comparisons to crew performance. ACKNOWLEDGEMENTS: The authors acknowledge contributions from Draper, the Dynamic Skills Trainer (DST) Lab, and the Software, Robotics, and Simulation Division toward the development of the lunar landing simulation platforms. This project is funded by the Human Health Countermeasures Element.

Hannah M. Weiss↗

Contrasting Perspectives Of Junior versus Senior NASA ISS Flight Controllers On Leadership And Cultural Issues

NASA flight controllers have always worked in a very demanding environment, but the International Space Station (ISS) poses even more challenges than prior missions. A recent NASA/Ames survey by Parke and Orasanu of NASA/Johnson flight controllers uncovered concerns about communications problems between American personnel and their international counterparts. To better understand these problems, we interviewed 14 senior and 12 junior ISS flight controllers at NASA/Johnson about leadership and cultural challenges they face and strategies for addressing these challenges. The qualitative interview data were coded and tabulated. Here we present quantitative analyses testing for differences between junior and senior controllers. Based on nonparametric statistical tests comparing responses across groups, the senior controllers were significantly more aware of the impact of working in dispersed teams, the context of constant change, and the upcoming multilateral challenges, while junior controllers were more aware of language and cultural issues. We consider our findings in light of other studies of controllers and other known differences between senior and junior controllers. For example, the fact that senior controllers had their formative early experience controlling pre-ISS short-duration Shuttle missions seems to have both positive and negative aspects, which are supported by our data. Our findings may also reflect gender differences, but we cannot unconfound this effect in our data because all the senior respondents were males. Many of the junior-senior differences are not only due to elapsed time on the job, but also due to a cohort effect. The findings of this study should be used for training curricula tailored differently for junior and senior controllers.

Clement, James L.↗

Do Astronauts Havbe a Higher Rate of Orthopedic Shoulder Conditions Than a Cohort of Working Professionals

Occupational surveillance of astronaut shoulder injuries began with operational concerns at the Neutral Buoyancy Laboratory (NBL) during Extra Vehicular Activity (EVA) training. Orthopedic shoulder injury and surgery rates were calculated [1], but classifying the rates as normal, high or low was highly dependent on the comparison group. Thus, the purpose of this study was to identify a population of working professionals and compare orthopedic shoulder consultation and surgery rates.

Laughlin, M. S.↗

Do Astronauts have a Higher Rate of Orthopedic Shoulder Conditions than a Cohort of Working Professionals?

Occupational surveillance of astronaut shoulder injuries began with operational concerns at the Neutral Buoyancy Laboratory (NBL) during Extra Vehicular Activity (EVA) training. NASA has implemented several occupational health initiatives during the past 20 years to decrease the number and severity of injuries, but the individual success rate is unknown. Orthopedic shoulder injury and surgery rates were calculated, but classifying the rates as normal, high or low was highly dependent on the comparison group. The purpose of this study was to identify a population of working professionals and compare orthopedic shoulder consultation and surgery rates.

Laughlin, Mitzi S.↗

A Community for Polar Early Career Researchers Engaging With the Interagency Arctic Research Policy Committee

The Interagency Arctic Research Policy Committee (IARPC) is tasked with implementation of the Arctic Research Plan (ARP) by coordinating representatives from federal and state agencies, academic, industry, and Indigenous partners with interests in Arctic research. IARPC is organized into several collaboration teams and discipline-specific communities of practice that interface on the IARPC Collaborations website. The Early Career Community of Practice (ECCoP) is one such community that was established to promote the research of early career researchers (ECR) and increase ECR engagement with the ARP, program managers, collaboration teams, and communities of practice. The ECCoP has grown to develop regular newsletters promoting recent ECR research publications ad sharing training, job, funding, and collaboration opportunities relevant to community members at all life stages that self-identify as ECRs. Within IARPC, the ECCoP continues to promote ECR participation in monthly community of practice meetings and webinars and to report on ECR efforts that contribute to deliverables of the ARP Biennial Implementation Plan. Recent activity of the ECCoP includes developing an annual survey of the ECR cohort on IARPC to follow change in demographics over time and to identify community needs to improve diversity and inclusion in the polar research space and to address gaps in training needs for ECRs.

Katy Smith↗

Improved pulmonary function in working divers breathing nitrox at shallow depths

INTRODUCTION: There is limited data about the long-term pulmonary effects of nitrox use in divers at shallow depths. This study examined changes in pulmonary function in a cohort of working divers breathing a 46% oxygen enriched mixture while diving at depths less than 12 m. METHODS: A total of 43 working divers from the Neutral Buoyancy Laboratory (NBL), NASA-Johnson Space Center completed a questionnaire providing information on diving history prior to NBL employment, diving history outside the NBL since employment, and smoking history. Cumulative dive hours were obtained from the NBL dive-time database. Medical records were reviewed to obtain the diver's height, weight, and pulmonary function measurements from initial pre-dive, first year and third year annual medical examinations. RESULTS: The initial forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were greater than predicted, 104% and 102%, respectively. After 3 yr of diving at the NBL, both the FVC and FEV1 showed a significant (p < 0.01) increase of 6.3% and 5.5%, respectively. There were no significant changes in peak expiratory flow (PEF), forced mid-expiratory flow rate (FEF(25-75%)), and forced expiratory flow rates at 25%, 50%, and 75% of FVC expired (FEF25%, FEF50%, FEF75%). Cumulative NBL dive hours was the only contributing variable found to be significantly associated with both FVC and FEV1 at 1 and 3 yr. CONCLUSIONS: NBL divers initially belong to a select group with larger than predicted lung volumes. Regular diving with nitrox at shallow depths over a 3-yr period did not impair pulmonary function. Improvements in FVC and FEV1 were primarily due to a training effect.

Non-programmatic↗

Results of a Prospective Echocardiography Trial in International Space Station Crew

In the framework of an operationally oriented investigation, we conducted a prospective trial of a standard clinical echocardiography protocol in a cohort of long-duration crewmembers. The resulting primary and processed data appear to have no precedents. Our tele-echocardiography paradigm, including just-in-time e-training methods, was also assessed. A critical review of the imaging technique, equipment and setting limitations, and quality assurance is provided, as well as the analysis of "space normal" data.

Hamilton, Douglas R.↗

Integrated Clinical Training for Space Flight Using a High-Fidelity Patient Simulator in a Simulated Microgravity Environment

This viewgraph presentation reviews the use of telemedicine in a simulated microgravity environment using a patient simulator. For decades, telemedicine techniques have been used in terrestrial environments by many cohorts with varied clinical experience. The success of these techniques has been recently expanded to include microgravity environments aboard the International Space Station (ISS). In order to investigate how an astronaut crew medical officer will execute medical tasks in a microgravity environment, while being remotely guided by a flight surgeon, the Medical Operation Support Team (MOST) used the simulated microgravity environment provided aboard DC-9 aircraft teams of crew medical officers, and remote flight surgeons performed several tasks on a patient simulator.

Hurst, Victor↗

Clinical Outcome Metrics for Optimization of Robust Training

Introduction: The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capability's (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-Flight Medical Capabilities." Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes. Methods: Medical simulations will systematically compare success of individual diagnostic and therapeutic procedure simulations performed by physician and non-physician crew medical officer (CMO) analogs using clearly defined short-term (individual procedure) outcome metrics. In the subsequent step of the project, the procedure simulation outcomes will be used as input to a modified version of the NASA Integrated Medical Model (IMM) to analyze the effect of the outcome (degree of success) of individual procedures (including successful, imperfectly performed, and failed procedures) on overall long-term clinical outcomes and the consequent mission impacts. The procedures to be simulated are endotracheal intubation, fundoscopic examination, kidney/urinary ultrasound, ultrasound-guided intravenous catheter insertion, and a differential diagnosis exercise. Multiple assessment techniques will be used, centered on medical procedure simulation studies occurring at 3, 6, and 12 months after initial training (as depicted in the following flow diagram of the experiment design). Discussion: Analysis of procedure outcomes in the physician and non-physician groups and their subsets (tested at different elapsed times post training) will allow the team to 1) define differences between physician and non-physician CMOs in terms of both procedure performance (pre-IMM analysis) and overall mitigation of the mission medical impact (IMM analysis); 2) refine the procedure outcome and clinical outcome metrics themselves; 3) refine or develop innovative medical training products and solutions to maximize CMO performance; and 4) validate the methods and products of this experiment for operational use in the planning, execution, and quality assurance of the CMO training process The team has finalized training protocols and developed a software training/testing tool in collaboration with Butler Graphics (Detroit, MI). In addition to the "hands on" medical procedure modules, the software includes a differential diagnosis exercise (limited clinical decision support tool) to evaluate the diagnostic skills of participants. Human subject testing will occur over the next year.

Ebert, D.↗

Clinical Outcome Metrics for Optimization of Robust Training

The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capabilities (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities". Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes.

Ebert, D.↗

NASA's Space Health Impacts for the NASA Experience (SHINE) Training Program – Space Radiation Curriculum

In February 2023, the Space Radiation Element of the NASA Human Research Program initiated a virtual, annual space radiation curriculum. The Space Health Impacts for the NASA Experience (SHINE) Space Radiation Didactic Curriculum aims to educate participants not only in the scientific aspects of space radiation but also in the agency’s risk management strategies. SHINE Space Radiation Didactic Curriculum combined weekly seminars by speakers from NASA, other government agencies, academia, and industry, with networking sessions designed to foster collaboration between the competitively selected participants as well as interactions with NASA scientists and HRP funded investigators. The inaugural course ran weekly from February 2023 to August 2023 and was comprised of lectures, less formal coffee hours, and office hours. Each two-hour seminar sessions hosted 1-3 presentations on topics which ranged from the space radiation environment to health effects and countermeasure to granting opportunities. All lectures were recorded and will be published on the THREE (The Health Risks of Extraterrestrial Environments) website for public access (https://three.jsc.nasa.gov/). As a course requirement, participants developed individual or collaborative beam time proposals for real, proposed, or potential experiments at the NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory. For the 2023 course, 25 participants were selected from a total of 59 applicants. Selected participants were citizens from 8 countries and comprised 5 graduate students, 4 postdocs, 11 scientists and 5 professors/medical doctors. Participants had a wide range of expertise including molecular and cellular biology, microbiology, botany, physiology, engineering, physics, aerospace medicine, planetary science, biostatistics, and modeling. The second annual SHINE training program is scheduled from February to August 2024. In addition, a separate SHINE Space Radiation Practicum session will be held in Fall 2024 at the NSRL. The SHINE Space Radiation Practicum is a unique opportunity that has not been available to the public since the closure of the NASA Space Radiation Summer School in 2017 and will allow a small cohort of participants competitively selected in Fall 2023 to gain hands-on radiation experience.

SHINE↗

Neuro-Vestibular Examination During and Following Spaceflight (Vestibular Health)

BACKGROUND Adaptation to microgravity during spaceflight causes neurological disturbances that are either directly or indirectly mediated by the vestibular system. These disturbances could include space motion sickness, spatial disorientation, and cognitive impairment, as well as changes in head-eye coordination, vestibulo-ocular reflexes, and control of posture and locomotion. Otolith-mediated reflex gains appear to adapt rapidly during spaceflight and after landing. However, animal studies have shown that structural modifications of the vestibular sensory apparatus develop during long-duration spaceflight. To date, no studies have characterized the severity of vestibular syndromes experienced by astronauts as a function of the duration of spaceflight or whether the effects are caused by changes at the peripheral end organs, midbrain, cerebellum, or vestibular cortex. OBJECTIVES We will investigate temporal vestibular changes in crewmembers of short, 6-month, and one-year missions to identify trends in adaptation of vestibular health and performance in orbit and after landing. We will also determine whether the vestibular organs and/or the central vestibular system undergo structural changes during long-duration exposure to microgravity, which could cause vestibular disorders when transitioning to a different gravitational environment. METHODS Recordings of eye, head, and body movements, as well as subjective reports of perception of motion, will be used to determine the presence of abnormal eye movements, dysmetria, motion sickness symptoms, and illusions of motion during head or body movements. This includes characterization of temporal trends in central compensation for vestibular (otolith) asymmetry. Pre-flight data will be collected 90 days before the flight. In-flight tests will be performed early in the mission and once every one or two months thereafter. Post-flight examinations will be performed on the following days after return (R) from the mission: R+0, R+4, R+9, and R+30. Ground-based control tests will be performed on healthy volunteers in the laboratory to estimate mean normative responses. CONTROL RESULTS Thirty-two healthy (non-astronaut) control subjects performed the same ground test procedures as planned for crewmembers. In addition to establishing a normative database, these data were used to calculate vestibular asymmetries from perceptual reports during unilateral centrifugation, oculomotor responses during visual-alignment tasks, vestibulo-ocular reflex gain during head-impulse tests, and body rotation during stepping tests. A significant correlation was observed between asymmetries of subjective visual vertical and verbal report during unilateral centrifugation. Another significant correlation was observed between the asymmetries of ocular alignment, vestibulo-ocular reflex gain, and body rotation. These findings in a healthy cohort may help us better understand changes in vestibular asymmetries in crewmembers during and following spaceflight. RELEVANCE If the observed symptoms in crewmembers are more deleterious after the year-long missions than those documented after 6-month missions, then relevant countermeasures will be required to maintain the health and operational performance of astronauts during longer missions. Depending on the etiology of the vestibular syndrome revealed by these tests, countermeasures will be proposed based on vestibular rehabilitation therapies currently used in patients with vestibular disorders, such as habituation, gaze stabilization, and/or balance training exercises. ACKNOWLEDGEMENT This work is supported by the NASA’s Human Research Program Human Health Countermeasures Element.

T R Macaulay↗

Psychosocial correlates of immune responsiveness and illness episodes in US Air Force Academy cadets undergoing basic cadet training

This study examined psychosocial correlates of immune function and illness in 89 male first-year US Air Force Academy cadets. A psychosocial questionnaire was administered to cadets prior to their arrival at the academy and was readministered during cadet orientation and during the stressful environment of Basic Cadet Training (BCT). Immune responsiveness was analyzed by PHA-, PMA-, or anti-CD3-stimulated thymidine uptake in mononuclear leucocytes. Illness episodes were assessed via medical chart review and self-reported symptoms. There were significant increases in distress levels as cadets entered BCT. No psychosocial measure assessed prior to arrival at the academy predicted level of PHA-, PMA-, and anti-CD3-stimulated thymidine uptake or risk of illness. However, hostility levels reported during BCT predicted risk of illness in the four weeks following psychosocial assessment (odds ratio = 7.1; 95% confidence interval: 1.4-36.1). Elevated response to environmental stressors and lower well-being levels also predicted impending illness, but only in the cohort of cadets who had not contracted food poisoning prior to assessment during BCT (OR = 9.3, CI = 1.9-46.7; OR = 0.09, CI = 0.02-0.53). These results suggest that self-report measures of hostility, response to environmental stressors and well-being may be useful predictors of impending illness episodes in males encountering high stress environments.

NASA Discipline Regulatory Physiology↗

Zoledronate Prevents Simulated Weightlessness-Induced Bone Loss in the Cancellous Compartment While Blunting the Efficacy of a Mechanical Loading Countermeasure

Astronauts using high-force resistance training while weightless show a high-turnover remodeling state within the skeletal system, with resorption and formation biomarkers being elevated. One countermeasure for the skeletal health of astronauts includes an antiresorptive of the bisphosphonate (BP) drug class. We asked, does the combination of an anti-resorptive and high-force exercise during weightlessness have negative effects on bone remodeling and strength? In this study, we developed an integrated model to mimic the mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hind limb unloading (HU) to simulate weightlessness. We hypothesized that ZOL prevents structural degradation from simulated weightlessness and that CL and ZOL interact to render CL less effective. Thirty-two C57BL/6 mice (male, 16 weeks old, n=8/group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45μg/kg), or saline vehicle (VEH), prior to the start of HU. The right tibia was axially compressed in vivo 60x/day to 9N (+1200μstrain on the periosteal surface) and repeated 3x/week during HU. Left tibiae served as a within subject, non-compressed control. Ex vivo μCT was performed on all subjects to determine cancellous and cortical architectural parameters. Static and dynamic histomorphometry were carried out for the left and right tibiae to determine osteoclast- and osteoblast relevant surfaces. Further, micro damage was assessed in select groups by basic-fuchsin staining to test whether CL had an effect. For all assays, a multivariate (2x2x2) ANCOVA model was used to account for body weight changes. Additionally, for the tibiae, we incorporated a random effect for the subject (hence, a mixed model) to account for observations of both left and right tibiae within each subject. P < 0.05 was considered significant. In the cancellous compartment of the proximal tibial metaphysis, we observed a main effect from each independent variable, as determined by structural and histomorphometric assays. Specifically, as expected, ZOL showed an increase in the cancellous bone volume to total volume fraction (BV/TV, +32%) and trabecular number (+18%) compared to the VEH. As expected, ZOL decreased osteoclast surface (OC/BS) by -45% compared to VEH. Surprisingly, ZOL reduced mineralizing surface (MS/BS) and bone formation rate (BFR), indicators of osteoblast activity, by -40% and -54%, respectively, compared to VEH. Altogether, ZOL-treated mice displayed a low turnover state of remodeling in the metaphysis. In the context of skeletal aging, we speculate that ZOL prevented age-related cancellous strut loss during the experiment. As a main effect, as expected, HU decreased BV/TV by - 31% via reductions in both trabecular thickness (-11%) and number (-22%) compared to NA controls. Additionally, HU decreased MS/BS by -38% and bone formation rate (BFR) by -50% compared to NA controls. Altogether, these data are consistent with structural degradation resulting from imbalanced remodeling that favors resorption. As a main effect, CL increased BV/TV by +15% via increased trabecular thickness (+12%) compared to the noncompressed limb. As expected, CL increased MS/BS (+20%) and BFR (+24%), indicating osteoblast mineralization contributed to bone gains. These data show that CL provided an anabolic stimulus to the cancellous tissue. We observed unique interactions in ZOL*CL and HU*CL. First, ZOL prevented CL-induced increases in BV/TV and trabecular number, as compared to VEH. In the context of skeletal aging, these data suggest no added benefit from CL in the ZOL-treated mice. Interestingly, no microdamage was observed in mice that were unloaded and treated with ZOL (independent of CL). Secondly, HU prevented CL-induced increases in BFR, as compared to NA controls. These data suggest that either exercise is less effective or the kinetics of formation are slower during simulated weightlessness. Osteoclast surface was unchanged by either treatment. Thus, in contrast to exercising astronauts, these data do not suggest a high-turnover state in the metaphysis. To assess mechanical properties as a function of HU or ZOL, we tested the left femur in three-point bending ex vivo. As expected, HU decreased stiffness (-30%) compared to NA, and ZOL increased stiffness compared to VEH (+28%). Interestingly, HU increased the post-yield displacement, related to collagenous tensile loading, compared to NA (+20%). ZOL increased yield force (+11%) and ultimate force (+17%), which seems to explain the significant effect of ZOL increasing total energy (work-to-fracture, +15%), while not affecting the post yield displacement. Taken together, ZOL did not have detrimental affect on mechanical properties. Our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. We conclude that Zoledronate was an effective countermeasure against weightlessness-induced bone loss, though zoledronate, as well as weightlessness, rendered exercise-related mechanical loading less effective.

bone↗

Spaceflight Associated Neuro-Ocular Syndrome: A Brief for Astronaut Candidates

INTRODUCTION: Spaceflight Associated Neuro-ocular Syndrome (SANS) was first described in 2011 as a clinical process involving degradation of visual acuity and structural changes of the eye when exposed to microgravity. This syndrome poses a risk to astronaut vision, safety, and mission performance, especially during extended-duration missions. The modern astronaut cohort is a diverse group of men and women including scientists, engineers, teachers, pilots, business professionals, and artists. Given their diverse backgrounds, it is imperative all crews are educated on SANS risks and potential countermeasures. This education must be comprehensive and easily understood, regardless of academic background or specific expertise. TOPIC: A PowerPoint was created to serve as a presentation and stand-alone educational aid for all astronaut candidates (ASCANS). This medium was chosen as it can be updated dynamically as new information emerges. The brief was split into sections to facilitate organized delivery of complex content in easy-to-understand components. Sections included descriptive statistics, signs and symptoms, outcomes, myths and ongoing research, countermeasures, ongoing surveillance, and unknown and future directions. More research is necessary in order to understand this syndrome, and without continued ASCAN participation in research, acquisition of data will not be possible. These efforts will become increasingly critical with deep space and exploration missions. APPLICATION: We recommend regular use of this brief for all ASCANS, and potentially veteran crewmembers, given the high risks and potentially poor outcomes associated with SANS. For ASCANS, recommendations include that this brief be provided at the start of their training, with a bi-annual refresher course for all astronauts. This ensures they are current on SANS information, given the dynamic nature of this syndrome. Additionally, this brief will be made available to all as a self-study aid, utilized as a refresher immediately prior to launch. It is anticipated that this brief will promote the health, safety, and wellbeing of professional and private crews alike, during and after long-duration spaceflight. RESOURCES: Brunstetter, T., Tarver, B., & Tsung, A. (2022, October). Spaceflight Associated Neuro-ocular Syndrome (Sans) and its Risk to Nasa Astronauts. JSC Aerospace Medicine Clerkship. Houston, TX; Lyndon B. Johnson Space Center. Laurie, S. S., Macias, B. R., Pardon, L. P., Brunstetter, T., Tarver, W. J., Gibson, C. R., Greenwald, S. H., Jasien, K. V., Mason, S., & Tsung, A. (2022). (rep.). Evidence Report: Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS). Houston, TX: National Aeronautics and Space Administration. Mader, T. H., Gibson, C. R., Pass, A. F., Kramer, L. A., Lee, A. G., Fogarty, J., ... & Polk, J. D. (2011). Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology, 118(10), 2058-2069. LEARNING OBJECTIVES: • The audience will be able to describe current Spaceflight Associated Neuro-ocular Syndrome (SANS) findings, significance, and countermeasures. • The audience will understand the importance of astronauts’ familiarity with SANS prior to flying and the large risks associated with this syndrome. CME QUESTIONS (3 QUESTIONS, MULTIPLE CHOICE A-D): 1. What is the approximate prevalence rate of SANS in astronauts? A. 22% B. 50% C. 66% D. 80% Answer: C. 2. Which of the ocular findings are NOT associated with SANS? A. Optic disc edema B. Retinal detachment C. Globe flattening D. Chorioretinal folds Answer: B. 3. Which of the following diagnostic technologies are NOT available in-flight? A. Ocular ultrasound B. Retinal photography C. MRI Orbit D. Optical Coherence Tomography (OCT) Answer: C.

Sara Stroble Mason↗