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At least 433 records · Page 24

Improvement in diastolic intraventricular pressure gradients in patients with HOCM after ethanol septal reduction

We sought to validate measurement of intraventricular pressure gradients (IVPG) and analyze their change in patients with hypertrophic obstructive cardiomyopathy (HOCM) after ethanol septal reduction (ESR). Quantitative analysis of color M-mode Doppler (CMM) images may be used to estimate diastolic IVPG noninvasively. Noninvasive IVPG measurement was validated in 10 patients undergoing surgical myectomy. Echocardiograms were then analyzed in 19 patients at baseline and after ESR. Pulsed Doppler data through the mitral valve and pulmonary venous flow were obtained. CMM was used to obtain the flow propagation velocity (Vp) and to calculate IVPG off-line. Left atrial pressure was estimated with the use of previously validated Doppler equations. Data were compared before and after ESR. CMM-derived IVPG correlated well with invasive measurements obtained before and after surgical myectomy [r = 0.8, P < 0.01, Delta(CMM - invasive IVPG) = 0.09 +/- 0.45 mmHg]. ESR resulted in a decrease of resting LVOT systolic gradient from 62 +/- 10 to 29 +/- 5 mmHg (P < 0.001). There was a significant increase in the Vp and IVPG (from 48 +/- 5to 74 +/- 7 cm/s and from 1.5 +/- 0.2 to 2.6 +/- 0.3 mmHg, respectively, P < 0.001 for both). Estimated left atrial pressure decreased from 16.2 +/- 1.1 to 11.5 +/- 0.9 mmHg (P < 0.001). The increase in IVPG correlated with the reduction in the LVOT gradient (r = 0.6, P < 0.01). Reduction of LVOT obstruction after ESR is associated with an improvement in diastolic suction force. Noninvasive measurements of IVPG may be used as an indicator of diastolic function improvement in HOCM.

NASA Program Biomedical Research and Countermeasur↗

Circadian rhythms in healthy aging--effects downstream from the pacemaker

Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

Non-NASA Center↗

Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions

We have developed a model of cardiac thin filament activation using an Ising model approach from equilibrium statistical physics. This model explicitly represents nearest-neighbor interactions between 26 troponin/tropomyosin units along a one-dimensional array that represents the cardiac thin filament. With transition rates chosen to match experimental data, the results show that the resulting force-pCa (F-pCa) relations are similar to Hill functions with asymmetries, as seen in experimental data. Specifically, Hill plots showing (log(F/(1-F)) vs. log [Ca]) reveal a steeper slope below the half activation point (Ca(50)) compared with above. Parameter variation studies show interplay of parameters that affect the apparent cooperativity and asymmetry in the F-pCa relations. The model also predicts that Ca binding is uncooperative for low [Ca], becomes steeper near Ca(50), and becomes uncooperative again at higher [Ca]. The steepness near Ca(50) mirrors the steep F-pCa as a result of thermodynamic considerations. The model also predicts that the correlation between troponin/tropomyosin units along the one-dimensional array quickly decays at high and low [Ca], but near Ca(50), high correlation occurs across the whole array. This work provides a simple model that can account for the steepness and shape of F-pCa relations that other models fail to reproduce.

Evaluation Studies↗

Space motion sickness medications: interference with biomedical parameters

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.

manned↗

Cryo2StructData: A Large Labeled Cryo-EM Density Map Dataset for AI-based Modeling of Protein Structures

The advent of single-particle cryo-electron microscopy (cryo-EM) has brought forth a new era of structural biology, enabling the routine determination of large biological molecules and their complexes at atomic resolution. The high-resolution structures of biological macromolecules and their complexes significantly expedite biomedical research and drug discovery. However, automatically and accurately building atomic models from high-resolution cryo-EM density maps is still time-consuming and challenging when template-based models are unavailable. Artificial intelligence (AI) methods such as deep learning trained on limited amount of labeled cryo-EM density maps generate inaccurate atomic models. To address this issue, we created a dataset called Cryo2StructData consisting of 7,600 preprocessed cryo-EM density maps whose voxels are labelled according to their corresponding known atomic structures for training and testing AI methods to build atomic models from cryo-EM density maps. Cryo2StructData is larger than existing, publicly available datasets for training AI methods to build atomic protein structures from cryo-EM density maps. We trained and tested deep learning models on Cryo2StructData to validate its quality showing that it is ready for being used to train and test AI methods for building atomic models.

59 BASIC BIOLOGICAL SCIENCES↗

Biomedical Results of the Space Shuttle Program

The Space Shuttle Program (SSP), which was triumphantly completed by the flight of STS-135 on July 21, 2011, holds a special place in the history of Human Space Exploration. For the first time, a vehicle was built that could perform multiple flights in space and return to Earth. Many important questions regarding the ability of humans to adapt and function in space have been answered during the 30 years since the SSP was launched and many lessons have been learned. The multidisciplinary studies conducted during this program allowed NASA to define the normal responses and potential pathologic changes of the major physiological systems to short-duration space flights. The program significantly contributed to the development of in-flight medical care capabilities and multiple countermeasures. A comprehensive system of preflight, in-flight, and post-flight monitoring of the astronauts was built. It is important to emphasize that the SSP was essential for building the International Space Station (ISS) that significantly expanded the boundaries of space research, allowing for planning of long-term near-terrestrial and extraterrestrial missions. As the program was coming to completion, a decision was made by the NASA Lyndon B. Johnson Space Center Human Research Program senior management to summarize the medico-biological results of the SSP in one comprehensive edition. This was quite an ambitious goal. It required selection of a group of experts in different areas to become the chapters lead authors. These experts were charged with the task of reviewing what was learned in the consequent fields to make the chapters a comprehensive source of information for planning of research, operational activities, and medical care for future missions. We hope that we were able to accomplish this goal and the book will serve as a reliable reference edition for the international space biomedicine community, for new generation of space researchers and Flight Surgeons, as well as for all those interested in space exploration. As space exploration continues, the major question of whether humans are capable of adapting to long-term presence and adequately functioning in space habitats will remain open for a long time. we expect that the comprehensive review of the medico-biological results of the SSP along with the data collected during the missions on the space stations (the Russian space station _Mir_ and ISS) provides a good starting point in seeking the answer to this question.

Diana Risin↗

Assessments of Physiology and Cognition in Hybrid-Reality Environments (APACHE)

NASA is planning to return to the Moon in the mid-2020s as a stepping stone to Mars missions in the 2030s. Spacewalks, or extravehicular activities (EVAs), performed on the Moon and Mars will differ in a variety of ways from those that have been performed in decades past. NASA has identified multiple risks to human health and performance associated with a crewed mission to Mars, especially those associated with exploration EVAs which are expected to be a primary mission activity. Crew may be expected to conduct up to 24 hours of EVA per person per week, where the likelihood of injury and/or mental mistakes are increased compared to ground-based training or current microgravity EVAs and the consequences of which can be catastrophic. Current test environments for exploration EVA research and technology development are large, costly facilities that are limited in their availability or capabilities. Spacesuit testing in a reduced gravity environment such as NASA’s Neutral Buoyancy Laboratory, while a good representation of the crew’s physical workload during exploration EVAs, typically has small datasets and is difficult to integrate physiological sensors or other types of crew performance measures. Meanwhile, scientific field-based testing such as NASA’s Desert Research and Technology Studies offers an operationally relevant environment for exploration EVAs, particularly for cognitive workload, but is also limited by small datasets, lack of a pressurized spacesuit, and obtrusive measures. The limitations of current analogs for exploration EVAs identify a need for a new test environment that can approximate both the physical and cognitive demands associated with exploration EVAs to enable rapid, controlled, and repeatable evaluations of human health and performance risks of exploration missions. In response, the Human Physiology, Performance, Protection, and Operations Laboratory (H-3PO) at NASA Johnson Space Center has developed a hybrid reality exploration EVA analog named the Assessments of Physiology And Cognition in Hybrid-reality Environments (APACHE) to address these limitations using a combination of virtual, physical, and hybrid reality techniques. The APACHE facility resides at NASA Johnson Space Center and serves as a large “sandbox” for EVA research and simulation. At its center is a roughly 15x20ft space surrounded by a 14” tall sandbox partially filled with lunar regolith simulant to emulate the physical feeling of walking on a planetary surface and to allow for simulated geology operations. Nearby, a curved passive treadmill (Skillmill Connect, Technogym, Fairfield, NJ) and an omnidirectional treadmill (Infinadeck, Infinadeck, Rocklin, CA) are included to enable exploration of these large virtual environments while also imposing the physical demands, representative timelines, and cognitive burdens required to navigate and traverse these distances during exploration EVA. A 6DOF motion platform is used to simulate rover operations and supports various human performance evaluations and associated risks. Lastly, APACHE can support two extravehicular (EV) crewmembers working in tandem. A computer workstation is located nearby and also supports an intravehicular (IV) crewmember as part of a full mission simulation. The IV crewmember has direct video and audio communication with the EV crew in VR to provide operational and procedural support. The software used in APACHE was created by the JSC Engineering Directorate, in partnership with Buendea, powered by a custom Unreal Engine 5 (UE5.3, Epic Games) project. APACHE currently utilizes the HTC Vive Pro Eye in a wireless configuration for VR simulations. There are two virtual environments that subjects can explore within APACHE, a Lunar and Martian surface. The virtual Lunar surface was created from LIDAR data of the Lunar South Pole to create roughly 16 sq km of explorable terrain. The virtual Martian surface contains roughly 400 sq km of explorable terrain derived from Mars Reconnaissance Orbiter LIDAR data of the Jezero Crater. The immersion and related cognitive burdens of conducting a planetary EVA is simulated through a series of EVA-relevant tasks performed in the VR environment, using these high-fidelity visual representations. Additionally, APACHE includes biosensor driven informatics, such as real-time heart rate monitoring and/or derived values from model simulations, for active monitoring by the EV crew and added cognitive demand. A “Wizard of Oz” control panel enables test operators to activate contingency events such as simulated spacesuit malfunctions, loss of communications, and/or limited visibility. Embedded performance measures such as accuracy, completeness, and execution time have been developed for various exploration tasks to objectively quantify crew performance during an EVA and compare impacts to performance when different environmental stressors, both physical and cognitive, are added to or removed from the simulation. Additionally, validated cognitive and operational performance measures such as the Digit Symbol Substitution Task have been recreated and embedded in VR for direct and relatively unobtrusive measurement of motor perception. The APACHE environment currently supports multiple research studies at NASA. Examples include the CHAPEA project, a series of simulated year-long missions on Mars by a 4-person crew; and the CO2 Contingency Walk Back Study, an investigation of elevated CO2 exposure on crew performance during a contingency EVA scenario. APACHE also provides a test environment to support the development of the Crew State and Risk Model, which is a collection of individualized, mathematical models of crew physical and cognitive state; and the Personalized EVA Informatics and Decision Support system, an operational tool for flight controllers, and eventually a self-reliant Martian crew, to make biomedically-informed decisions in real-time to optimize the EVA planning and execution with respect to crew health and performance. Some technical challenges associated with developing the APACHE environment, as well as current limitations, include VR limitless natural walking with a hybrid spacesuit simulator, optimizing performance for wireless PC VR streaming while maintaining a high degree of visual fidelity, and the integration of various physiological (metabolic masks) and psychometric (eye tracking) sensors with the VR headset.

Human Performance↗

Core Body Temperature Predictions Using Metabolic Energy Expenditure and Heart Rate During Simulated Extravehicular Activity

Long duration spaceflight missions will require crew to become more autonomous in conducting extravehicular activities (EVA) without direct communication with Mission Control for biomedical support. To enable such autonomy, we are developing a Crew State and Risk Model (CSRM) as a collection of key physiology domains that drive EVA crew capabilities and workloads. One model component of CSRM is human thermal regulation. In this paper, customized development of a baseline model to predict core body temperature is presented using physiology inputs of heart rate and metabolic rate. The model development dataset included a baseline study where participants (n=6, equal male and female) performed a 5-hour EVA in a two-part session while wearing a hybrid space suit simulator (HS3). The first session included an end-to-end EVA traversing 1500 meters to a geology site and traversing back to a habitat conducting geology, payload relocation, and maintenance operations every 500 meters. The second session included standalone tasks of a 2000-meter traverse followed by geology tasks. Thermal measures of core body temperature, local skin temperature, liquid cooling garment temperature, heart rate, and metabolic rate were collected through the test duration. Multiple regression was used to build a linear equation to predict core body temperature from inputs of heart rate and metabolic rate. Heat storage was calculated via predicted core body temperature plus LCG and skin temperatures. The model was tested against a dataset from a pressurized suited test (n=6, equal male and female) in the NASA Active Response Gravity Offload System (ARGOS) conducting similar end-to-end EVA and standalone tasks. Predicted error of the model against the raw test cases was 0.2±0.15 °C. The baseline prediction of core body temperature using heart rates and metabolic rates allows for simple real-time tracking from data collected in-flight to monitor crew consumables and thermal flight limits during EVA.

Bradley Hoffmann↗

Calcaneal loading during walking and running

PURPOSE: This study of the foot uses experimentally measured kinematic and kinetic data with a numerical model to evaluate in vivo calcaneal stresses during walking and running. METHODS: External ground reaction forces (GRF) and kinematic data were measured during walking and running using cineradiography and force plate measurements. A contact-coupled finite element model of the foot was developed to assess the forces acting on the calcaneus during gait. RESULTS: We found that the calculated force-time profiles of the joint contact, ligament, and Achilles tendon forces varied with the time-history curve of the moment about the ankle joint. The model predicted peak talocalcaneal and calcaneocuboid joint loads of 5.4 and 4.2 body weights (BW) during walking and 11.1 and 7.9 BW during running. The maximum predicted Achilles tendon forces were 3.9 and 7.7 BW for walking and running. CONCLUSIONS: Large magnitude forces and calcaneal stresses are generated late in the stance phase, with maximum loads occurring at approximately 70% of the stance phase during walking and at approximately 60% of the stance phase during running, for the gait velocities analyzed. The trajectories of the principal stresses, during both walking and running, corresponded to each other and qualitatively to the calcaneal trabecular architecture.

NASA Center ARC↗

Hypergravity-induced immunomodulation in a rodent model: lymphocytes and lymphoid organs

The major goal of this study was to quantify changes in lymphoid organs and cells over time due to centrifugation-induced hypergravity. C57BL/6 mice were exposed to 1, 2 and 3 G and the following assays were performed on days 1, 4, 7, 10, and 21: spleen, thymus, lung, and liver masses; total leukocyte, lymphocyte, monocyte/macrophage, and granulocyte counts; level of splenocyte apoptosis; enumeration of CD3+ T, CD3+/CD4+ T helper, CD3+/CD8+ T cytotoxic, B220+ B, and NK1.1+ natural killer cells; and quantification of cells expressing CD25, CD69, and CD71 activation markers. The data show that increased gravity resulted in decreased body, spleen, thymus, and liver, but not lung, mass. Significant reductions were noted in all three major leukocyte populations (lymphocytes, granulocytes, monocyte/macrophages) [correction of macrphages] with increased gravity; persistent depletion was noted in blood but not spleen. Among the various lymphocyte populations, the CD3+/CD8+ T cells and B220+ B cells were the most affected and NK1.1+ NK cells the least affected. Overall, the changes were most evident during the first week, with a greater influence noted for cells in the spleen. A linear relationship was found between some of the measurements and the level of gravity, especially on day 4. These findings indicate that hypergravity profoundly alters leukocyte number and distribution in a mammalian model and that some aberrations persisted throughout the three weeks of the study. In certain cases, the detected changes were similar to those observed after whole-body irradiation. In future investigations we hope to combine hypergravity with low-dose rate irradiation and immune challenge.

Non-NASA Center↗

Space Discovery: Teaching with Space. Evaluation: Summer, Fall 1998 Programs

This is the final report of the 1998 NASA-sponsored evaluation of the effectiveness of the United States Space Foundation's five-day Space Discovery Standard Graduate Course (Living and Working in Space), the five-day Space Discovery Advanced Graduate Course (Advanced Technology and Biomedical Research), the five-day introductory course Aviation and Space Basics all conducted during the summer of 1998, and the Teaching with Space two-day Inservice program. The purpose of the program is to motivate and equip K- 12 teachers to use proven student-attracting space and technology concepts to support standard curriculum. These programs support the America 2000 National Educational Goals, encouraging more students to stay in school, increase in competence, and have a better opportunity to be attracted to math and science. The 1998 research program continues the comprehensive evaluation begun in 1992, this year studying five summer five-day sessions and five Inservice programs offered during the Fall of 1998 in California, Colorado, New York, and Virginia. A comprehensive research design by Dr. Robert Ewell of Creative Solutions and Dr. Darwyn Linder of Arizona State University evaluated the effectiveness of various areas of the program and its applicability on diverse groups. Preliminary research methodology was a set of survey instruments administered after the courses, and another to be sent in April-4-5 months following the last inservice involved in this study. This year, we have departed from this evaluation design in two ways. First, the five-day programs used NASA's new EDCATS on-line system and associated survey rather than the Linder/Ewell instruments. The Inservice programs were evaluated using the previously developed survey adapted for Inservice programs. Second, we did not do a follow-on survey of the teachers after they had been in the field as we have done in the past. Therefore, this evaluation captures only the reactions of the teachers to the programs immediately after the instruction. Although EDCATS is designed for teachers to enter their data logged onto the appropriate internet web site, most surveys were completed on a printed copy and entered into the EDCATS system by USSF personnel. The Aviation and Space Basics class were taken to a computer lab where they responded to the survey on-line. Data from the Inservice surveys were manually entered into a computer spreadsheet program by US Space Foundation personnel and processed using the statistical program SPSS for Windows. The raw data and copy of the EDCATS survey for the five-day programs are in Appendix 1. The raw data and copy of the Inservice survey are in Appendix 2. Comments from both programs are in Appendices 3 and 4, respectively.

Ewell, Bob↗

A Route to Design Novel Functional Peptides by Applying a Denoising Diffusional Model to mRNA Display Libraries

In vitro directed evolution techniques, such as mRNA display, enable peptide ligand discovery and optimization. However, physical libraries that rely on a genetic code can only search a small fraction of sequence space due to inherent biases in the genetic code and experimental limitations. To address this challenge, denoising diffusion implicit models (DDIMs) are applied to generate novel peptide ligands against B‐cell lymphoma extra‐large (Bcl‐x L ), a key cancer target. Starting with high‐throughput sequencing data from previous selections, a DDIM is trained to produce novel sequences with high affinity binding. Experimental validation confirms that most generated sequences are functionally equivalent to the original library members for Bcl‐x L binding and demonstrated comparable binding kinetics and affinity relative to the wildtype and nearest original neighbors. Importantly, this approach generated rare sequences not easily accessible via mutation and directed evolution. These results indicate that DDIMs can complement and expand directed evolution data, efficiently exploring underrepresented regions of sequence space. This approach provides a broadly applicable framework for accelerating ligand discovery and optimizing molecular properties across diverse targets.

Qi, Pearl [Mork Family Department of Chemical Engi↗

2014 Space Radiation Standing Review Panel

The 2014 Space Radiation Standing Review Panel (from here on referred to as the SRP) participated in a WebEx/teleconference with members of the Space Radiation Program Element, representatives from the Human Research Program (HRP), the National Space Biomedical Research Institute (NSBRI), and NASA Headquarters on November 21, 2014 (list of participants is in Section XI of this report). The SRP reviewed the updated Research Plan for the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure (Degen Risk). The SRP also received a status update on the Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS Risk), the Risk of Acute Radiation Syndromes Due to Solar Particle Events (ARS Risk), and the Risk of Radiation Carcinogenesis (Cancer Risk). The SRP thought the teleconference was very informative and that the Space Radiation Program Element did a great job of outlining where the Element is with respect to our state of knowledge on the risks of carcinogenesis, central nervous system effects, and the risk of cardiovascular disease and other degenerative tissue effects from exposure to space radiation. The SRP was impressed with the quality of research that is being conducted and the progress the Space Radiation Program Element has made in the past year. While much work has been done, the SRP had a few remaining questions regarding the broad applicability of these findings to a manned deep space mission (in terms of cognitive function, the paradigms were still hippocampal based and also using Alzheimer disease models). The SRP believes that NASA should consider developing an approach to follow astronauts long-term (beyond retirement) for potential side-effects/risks of space exposure that may be unknown. Radiation toxicities often occur decades after exposure, and potential consequences would be missed if intensified exams stop after retirement of the astronauts. In addition, while cancer is one consequence of radiation exposure that is monitored, potential other side effects (CNS, Alzheimer Disease, loss of cognitive function, etc.) are not included in long-term studies and would be missed. Inclusion of long-term data would be of benefit to the astronauts themselves who have given their service to the corps but also to future astronauts and the future of space exploration.

Steinberg, Susan↗

Preliminary Sensorimotor and Cardiovascular Results from the Joint Russian and U.S. Pilot Field Test with Planning for the Full Field Test Beginning with the Year Long Intenational Space Station

Ongoing collaborative research efforts between NASA's Neuroscience and Cardiovascular Laboratories, and the Institute of Biomedical Problems' (IBMP) Sensory-Motor and Countermeasures Laboratories have been measuring functional sensorimotor, cardiovascular and strength responses following bed rest, dry immersion, short duration (Space Shuttle) and long duration (Mir and International Space Station) space flights. While the unloading paradigms associated with dry immersion and bed rest does serve as acceptable flight analogs, testing of crew responses following the long duration flights previously has not been possible until a minimum of 24 hours after landing. As a result, it is not possible to estimate the nonlinear trend of the early (<24 hr) recovery process, nor is it possible to accurately assess the full impact of the decrements associated with long duration flight. To overcome these limitations, both the Russian and U.S. sides have implemented testing at landing site. By joint agreement, this research effort has been identified as the functional Field Test (FT). For practical reasons the FT has been divided into two phases: the full FT and a preliminary pilot version (PFT) of the FT that is reduced in both length and scope. The primary goal of this research is to determine functional abilities in long duration space flight crews beginning as soon after landing as possible (< 2 hr) with one to three immediate follow-up measurements on the day of landing. This goal has both sensorimotor and cardiovascular elements, including evaluations of NASA's new anti-orthostatic compression garment and the Russian Kentavr garment. Functional sensorimotor measurements will include, but are not limited to, assessment of hand/eye coordination, ability to egress from a seated position, walk normally without falling, measurement of dynamic visual acuity, ability to discriminate different forces generated with both the hands and legs, recovery from a fall, a coordinated walk involving tandem heel-to-toe placement, and determination of postural ataxia while standing. The cardiovascular portion of the investigation includes blood pressure and heart rate measurements during a timed stand test in conjunction with postural ataxia testing (quiet stance sway) as well as cardiovascular responses during other functional tasks. In addition to the immediate post-landing collection of data for the full FT, postflight data will be acquired at a minimum of one to three more other times within the 24 hr following landing and continue until functional sensorimotor and cardiovascular responses have returned to preflight normative values. The PFT represents a single trial run comprised of jointly agreed upon subset of tests from the full FT and relies heavily on IBMP's Sensory-Motor and Countermeasures Laboratories for content and implementation. The PFT was first conducted following the September 2013 landing of the Soyuz spacecraft (34S) and again following the landing of Soyuz 35S in November. Testing included: (1) a sit-tostand test, (2) recovery from a fall where the crewmember began in the prone position on the ground and then stood for 3 min while cardiovascular stability was determined and postural ataxia data were acquired, and (3) a tandem heel-to-toe walk test to determine changes in the central locomotor program. Video, cardiovascular parameters (heart rate and blood pressure), data from body-worn inertial sensors and severity of postflight motion sickness were collected for analysis. In summary, the level of functional deficit is expected to be most profound during the acquisition of gravity loads immediately after landing when the demands for crew intervention in response to emergency operations will be greatest. Clearly measureable performance parameters such as ability to perform a seat egress, recover from a fall or the ability to see clearly when walking, and related physiological data (orthostatic responses) are required to provide an evidence base for characterizing programmatic risks and the degree of variability among crewmembers for exploration missions where the crew will be unassisted after landing. Overall, these early functional and related physiological measurements will allow estimation of nonlinear sensorimotor and cardiovascular recovery trends to an accuracy that has not been previously captured in over 50 years of space flight.

Reschke, M. F.↗

Preliminary Results from the Joint Russian and US Field Test: Measurement of Sensorimotor and Cardiovascular Responses Immediately Following Landing of the Soyuz Spacecraft

Ongoing collaborative research efforts between NASA's Neuroscience and Cardiovascular Laboratories, and the Institute of Biomedical Problems' (IBMP) Sensory-Motor and Countermeasures Laboratories have been measuring functional sensorimotor, cardiovascular and strength responses following bed rest, dry immersion, short duration (Space Shuttle) and long duration (Mir and International Space Station) space flights. While the unloading paradigms associated with dry immersion and bed rest have do serve as acceptable flight analogs, testing of crew responses following the long duration flights does not begin until a minimum of 24 hours after landing. As a result it is not possible to estimate the nonlinear trend of the early (<24 hr) recovery process nor is it possible to accurately assess the full impact of the decrements associated with long duration flight. To overcome these limitations both the Russian and U.S. sides have implemented testing at the time of landing and before the flight crews have left the landing site. By joint agreement this research effort has been identified as the functional Field Test (FT). For practical reasons the FT has been divided into two phases: the full FT and a preliminary pilot version (PFT) of the FT that is reduced in both length and scope. The primary goal of this research is to determine functional abilities in long duration space flight crews beginning as soon after landing as possible (< 2 hr) with one to three immediate follow-up measurements on the day of landing. This goal has both sensorimotor and cardiovascular elements including an evaluation of NASA's new anti-orthostatic compression garment as compared with the Russian Kentavr garment. Functional sensorimotor measurements will include, but are not limited to, assessment of hand/eye coordination, ability to egress from a seated position, walk normally without falling, measurement of dynamic visual acuity, ability to discriminate different forces generated with both the hands and legs, recovery from a fall, a coordinated walk involving tandem heel-to-toe placement and determination of postural ataxia while standing. The cardiovascular portion of the investigation includes blood pressure and heart rate measurements during a timed stand test in conjunction with postural ataxia testing. In addition to the immediate post-landing collection of data for the full FT, postflight data will be acquired at a minimum of one to three more other times within the 24 hr following landing and continue until functional sensorimotor and cardiovascular responses have returned to preflight normative values. The PFT represents a single trial run comprised of jointly agreed tests from the full FT and relies heavily on IBMP's Sensory-Motor and Countermeasures Laboratories for content, and implementation. The PFT is currently scheduled for the September 2013 landing of the Soyuz spacecraft (34S). Testing will include: (1) a sit-to-stand test, (2) recovery from a fall where the crewmember begins in the prone position on the ground and then stands for 3 min while cardiovascular stability is determined and postural ataxia data are acquired, and (3) a tandem heel-to-toe walk to determine changes in the central locomotor program. Video, cardiovascular parameters (heart rate and blood pressure), data from body-worn inertial sensors and severity of postflight motion sickness will be available for analysis. It is our intent to present, at this celebratory symposium, a summary of these data obtained from two crewmembers. In summary, the level of functional deficit is expected to be most profound during the acquisition of gravity loads immediately after landing when the demands for crew intervention in response to emergency operations will be greatest. Clearly measureable performance parameters such as ability to perform a seat egress, recover from a fall or the ability to see clearly when walking, and related physiological data (orthostatic responses) are required to provide an evidence base for characterizing programmatic risks and the degree of variability among crewmembers. Overall, these early functional and related physiological measurements will allow estimation of nonlinear sensorimotor and cardiovascular recovery trends to an accuracy that has not been previously captured in over 50 years of space flight.

Reschke, M. F.↗

Preliminary Sensorimotor and Cardiovascular Results from the Joint Russian/U.S. Pilot Field Test in Preparation for the Full Field Test

Ongoing collaborative research efforts between NASA's Neuroscience and Cardiovascular Laboratories, and the Institute of Biomedical Problems' (IBMP) Sensory-Motor and Countermeasures Laboratories have been measuring functional sensorimotor, cardiovascular and strength responses following bed rest, dry immersion, short-duration (Space Shuttle) and long-duration (Mir and International Space Station [ISS]) space flights. While the unloading paradigms associated with dry immersion and bed rest does serve as acceptable flight analogs, testing of crew responses following the long-duration flights previously has not been possible until a minimum of 24 hours after landing. As a result, it is not possible to estimate the nonlinear trend of the early (<24 hours) recovery process nor is it possible to accurately assess the full impact of the decrements associated with long-duration flight. To overcome these limitations, both the Russian and U.S. programs have implemented testing at the landing site. By joint agreement, this research effort has been identified as the functional Field Test (FT). For practical reasons the FT has been divided into two phases: the full FT and a preliminary pilot version (PFT) of the FT that is reduced in both length and scope. The primary goal of this research is to determine functional abilities in long-duration space-flight crews beginning as soon after landing as possible (< 2 hours) with one to three immediate follow-up measurements on the day of landing. This goal has both sensorimotor and cardiovascular elements, including evaluations of NASA's new anti-orthostatic compression garment and the Russian Kentavr garment. Functional sensorimotor measurements will include, but are not limited to, assessing hand/eye coordination, egressing from a seated position, walking normally without falling, measuring of dynamic visual acuity, discriminating different forces generated with both the hands and legs, recovering from a fall, coordinated walking involving tandem heel-to-toe placement, and determining postural ataxia while standing. The cardiovascular portion of the investigation includes measuring blood pressure and heart rate during a timed stand test in conjunction with postural ataxia testing (quiet stance sway) as well as cardiovascular responses during the other functional tasks. In addition to the immediate post-landing collection of data for the full FT, postflight data will be acquired between one and three more other times within the 24 hours after landing and will continue over the subsequent weeks until functional sensorimotor and cardiovascular responses have returned to preflight normative values. The PFT represents a single trial run comprised of a jointly agreed upon subset of tests from the full FT and relies heavily on IBMP's Sensory-Motor and Countermeasures Laboratories for content and implementation. The PFT has been collected on several ISS missions. Testing included: (1) a sit-to-stand test, (2) recovery from a fall where the crewmember began in the prone position on the ground and then stood for 3 minutes while cardiovascular stability was determined and postural ataxia data were acquired, and (3) a tandem heel-totoe walk test to determine changes in the central locomotor program. Video, cardiovascular parameters (heart rate and blood pressure), data from body-worn inertial sensors, and severity of postflight motion sickness were collected for each test session. In summary, the level of functional deficit is expected to be most profound during the acquisition of gravity loads immediately after landing when the demands for crew intervention in response to emergency operations will be greatest. Clearly measureable performance parameters such as ability to perform a seat egress, recover from a fall or the ability to see clearly when walking, and related physiologic data (orthostatic responses) are required to provide an evidence base for characterizing programmatic risks and the degree of variability among crewmembers for exploration missions where the crew will be unassisted after landing. Overall, these early functional and related physiologic measurements will allow estimation of nonlinear sensorimotor and cardiovascular recovery trends that has not been previously captured in over 50 years of space flight.

Reschke, M. F.↗

Oxidant damage during and after spaceflight

The objectives of this study were to assess oxidant damage during and after spaceflight and to compare the results against bed rest with 6 degrees head-down tilt. We measured the urinary excretion of the F(2) isoprostane, 8-iso-prostaglandin (PG) F(2alpha), and 8-oxo-7,8-dihydro-2 deoxyguanosine (8-OH DG) before, during, and after long-duration spaceflight (4-9 mo) on the Russian space station MIR, short-duration spaceflight on the shuttle, and 17 days of bed rest. Sample collections on MIR were obtained between 88 and 186 days in orbit. 8-iso-PGF(2alpha) and 8-OH DG are markers for oxidative damage to membrane lipids and DNA, respectively. Data are mean +/- SE. On MIR, isoprostane levels were decreased inflight (96. 9 +/- 11.6 vs. 76.7 +/- 14.9 ng. kg(-1). day(-1), P < 0.05, n = 6) due to decreased dietary intake secondary to impaired thermoregulation. Isoprostane excretion was increased postflight (245.7 +/- 55.8 ng. kg(-1). day(-1), P < 0.01). 8-OH DG excretion was unchanged with spaceflight and increased postflight (269 +/- 84 vs 442 +/- 180 ng. kg(-1). day(-1), P < 0.05). On the shuttle, 8-OH DG excretion was unchanged in- and postflight, but 8-iso-PGF(2alpha) excretion was decreased inflight (15.6 +/- 4.3 vs 8.0 +/- 2.7 ng. kg(-1). day(-1), P < 0.05). No changes were found with bed rest, but 8-iso-PGF(2alpha) was increased during the recovery phase (48.9 +/- 23.0 vs 65.4 +/- 28.3 ng. kg(-1). day(-1), P < 0.05). The changes in isoprostane production were attributed to decreased production of oxygen radicals from the electron transport chain due to the reduced energy intake inflight. The postflight increases in the excretion of the products of oxidative damage were attributed to a combination of an increase in metabolic activity and the loss of some host antioxidant defenses inflight. We conclude that 1) oxidative damage was decreased inflight, and 2) oxidative damage was increased postflight.

Mir Project↗

Rodent Habitat on ISS: Advances in Capability for Determining Spaceflight Effects on Mammalian Physiology

Rodent research is a valuable essential tool for advancing biomedical discoveries in life sciences on Earth and in space. The National Research Counsel's Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, new flight hardware, operations, and science capabilities were developed at NASA ARC to support commercial and government-sponsored research. The flight phases of two separate spaceflight missions (Rodent Research-1 and Rodent Research-2) have been completed and new capabilities are in development. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 was dedicated to achieving both NASA validation and CASIS science objectives, while Rodent Reesearch-2 extended the period on orbit to 60 days. Groundbased control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis, and post-flight quantitative analyses of behavior were performed. The 10 mice from RR-1 Validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully, and high quality RNA (RIN values>9) and liver enzyme activities were obtained, validating the quality of sample recovery. Post-flight sample analysis revealed that body weights of FLT animals did not differ from ground controls (GC) housed in the same hardware, or vivarium controls (VIV) housed in standard cages. Organ weights analyzed post-flight showed that there were no differences between FLT and GC groups in adrenal gland and spleen weights, whereas FLT thymus and liver weights exceeded those of GC. Minimal differences between the control groups (GC and VIV) were observed. In addition, Over 3,000 aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for the Biospecimen Sharing Program and Genelab project. New capabilities recently developed include DEXA scanning, grip strength tests and male mice. In conclusion, new capability for long duration rodent habitation of group-housed rodents was developed and includes in-flight sample collection, thus avoiding the complication of reentry. Results obtained to date reveal the possibility of striking differences between the effects of short duration vs. long duration spaceflight. This Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space.

Bone Loss↗