Evaluation of the Fluids Mixing Enclosure System for Life Science Experiments During a Commercial Caenorhabditis elegans Spaceflight Experiment.

The Student Spaceflight Experiments Program (SSEP) is a United States national science, technology, engineering, and mathematics initiative that aims to increase student interest in science by offering opportunities to perform spaceflight experiments. The experiment detailed here was selected and flown aboard the third SSEP mission and the first SSEP mission to the International Space Station (ISS). Caenorhabditis elegans is a small, transparent, self-fertilizing hermaphroditic roundworm that is commonly used in biological experiments both on Earth and in Low Earth Orbit. Past experiments have found decreased expression of mRNA for several genes whose expression can be controlled by the FOXO transcription factor DAF-16. We flew a daf-16 mutant and control worms to determine if the effects of spaceflight on C. elegans are mediated by DAF-16. The experiment used a Type Two Fluids Mixing Enclosure (FME), developed by Nanoracks LLC, and was delivered to the ISS aboard the SpaceX Dragon and returned aboard the Russian Soyuz. The short time interval between experiment selection and the flight rendered preflight experiment verification tests impossible. In addition, published research regarding the viability of the FME in life science experiments was not available. The experiment was therefore structured in such a way as to gather the needed data. Here we report that C. elegans can survive relatively short storage and activation in the FME but cannot produce viable populations for post-flight analysis on extended missions. The FME appears to support short-duration life science experiments, potentially on supply or crew exchange missions, but not on longer ISS expeditions. Additionally, the flown FME was not properly activated, reportedly due to a flaw in training procedures. We suggest that a modified transparent FME could prevent similar failures in future flight experiments.

Gravity's effect on biology.

Gravity is a fundamental interaction that permeates throughout our Universe. On Earth, gravity gives weight to physical objects, and has been a constant presence throughout terrestrial biological evolution. Thus, gravity has shaped all biological functions, some examples include the growth of plants (e.g., gravitropism), the structure and morphology of biological parts in multicellular organisms, to its effects on our physiological function when humans travel into space. Moreover, from an evolutionary perspective, gravity has been a constant force on biology, and life, to our understanding, should have no reason to not experience the effects of gravity. Interestingly, there appear to be specific biological mechanisms that activate in the absence of gravity, with the space environment the only location to study the effects of a lack of gravity on biological systems. Thus, in this perspective piece, biological adaptations from the cellular to the whole organism levels to the presence and absence of gravity will be organized and described, as well as outlining future areas of research for gravitational biological investigations to address. Up to now, we have observed and shown how gravity effects biology at different levels, with a few examples including genetic (e.g., cell cycle, metabolism, signal transduction associated pathways, etc.), biochemically (e.g., cytoskeleton, NADPH oxidase, Yes-associated protein, etc.), and functionally (e.g., astronauts experiencing musculoskeletal and cardiovascular deconditioning, immune dysfunction, etc., when traveling into space). Based from these observations, there appear to be gravity-sensitive and specific pathways across biological organisms, though knowledge gaps of the effects of gravity on biology remain, such as similarities and differences across species, reproduction, development, and evolutionary adaptations, sex-differences, etc. Thus, here an overview of the literature is provided for context of gravitational biology research to-date and consideration for future studies, as we prepare for long-term occupation of low-Earth Orbit and cis-Lunar space, and missions to the Moon and Mars, experiencing the effects of Lunar and Martian gravity on biology, respectively, through our Artemis program.

Effect of acute hypercapnia during 10-day hypoxic bed rest on posterior eye structures.

To gain insights into microgravity-induced ophthalmic changes (microgravity ocular syndrome), and as part of a project investigating effects of future planetary habitats, we investigated the effect of acute hypercapnia following 10-day bed rest and hypoxia on posterior eye structures. Female subjects (N = 7) completed three 10-day experimental interventions: 1) normoxic bed rest [NBR; partial pressure of inspired O2 (PiO2 ) = 132.9 ± 0.3 Torr]; 2) hypoxic ambulatory confinement (HAMB; PiO2 = 90.4 ± 0.3 Torr); and 3) hypoxic bed rest (HBR; n = 12; PiO2 = 90.4 ± 0.3 Torr). Before and on the last day of each intervention, optical coherence tomography (OCT) of the optic disk was performed, and the thicknesses of the retinal nerve fiber layer (RNFL), retina, and choroid were measured. OCT examinations were conducted with the subjects breathing the prevailing normocapnic breathing mixture (either normoxic or hypoxic) and then following a 10-min period of breathing the same gas mixture, but with the addition of 1% CO2 Choroidal thickness was greater during both bed-rest conditions (NBR and HBR) compared with the ambulatory (HAMB) condition (ANOVA, P < 0.001). Increases in RNFL thickness compared with baseline were observed in the hypoxic trials (HBR, P < 0.001; and HAMB, P = 0.021), but not the normoxic trial (NBR). A further increase in RNFL thickness (P = 0.019) was observed after the 10-min hypercapnic trial in the NBR condition only. The fact that choroidal thickness was not affected by Po2 or Pco2, but increased by bed rest, suggests a hydrostatic rather than a vasoactive effect. The increments in RNFL thickness were most likely associated with local hypoxia and hypercapnia-induced dilatation of the retinal blood vessels.

A multiparameter wearable physiologic monitoring system for space and terrestrial applications.

A novel, unobtrusive and wearable, multiparameter ambulatory physiologic monitoring system for space and terrestrial applications, termed LifeGuard, is presented. The core element is a wearable monitor, the crew physiologic observation device (CPOD), that provides the capability to continuously record two standard electrocardiogram leads, respiration rate via impedance plethysmography, heart rate, hemoglobin oxygen saturation, ambient or body temperature, three axes of acceleration, and blood pressure. These parameters can be digitally recorded with high fidelity over a 9-h period with precise time stamps and user-defined event markers. Data can be continuously streamed to a base station using a built-in Bluetooth RF link or stored in 32 MB of on-board flash memory and downloaded to a personal computer using a serial port. The device is powered by two AAA batteries. The design, laboratory, and field testing of the wearable monitors are described.

Evaluation of surgical skills in microgravity using force sensing.

INTRODUCTION: Force measurements can be used to characterize surgical maneuvers in microgravity. METHODS: : A series of surgical tasks was performed by a group of 20 participants (n=20) both in 1g on the ground and in 0 g aboard NASA's KC-135 aircraft in parabolic flight. The group included astronauts, a flight surgeon, surgeons, physicians, Ph.D.-scientists, and technical personnel. The interaction forces between the surgical instruments and the mock tissue were measured for a clip-applying, suturing, grasping, and cutting. Seven evaluations in 1g and a single evaluation in 0 g were performed by each of the participants. RESULTS: The data from a single participant are examined in detail. Statistical results for the group of 20 participants do not show significant differences in the average or peak forces during clip-applying or in the average forces applied during suturing in 0 g versus in 1g. However, the results do show statistically greater (43% higher) peak forces during suturing in microgravity. DISCUSSION: These data show the usefulness of analyzing force information to assess surgical task performance in microgravity. Although peak suturing forces were statistically higher in microgravity, their clinical relevance is unknown, but likely would not result in a change in clinical outcome. Overall, the data suggest that forces exerted during surgical tasks will not pose a significant barrier to effective surgery in microgravity.

User interface paradigms for patient-specific surgical planning: lessons learned over a decade of research.

This paper covers work in virtual reality-based, patient-specific surgical planning over the past decade. It aims to comprehensively examine the user interface paradigms and system designs during that period of time and to objectively analyze their effectiveness for the task. The goal is to provide useful feedback on these interface and implementation paradigms to aid other researchers in this field. First, specialized systems for specific clinical use were produced with a limited set of visualization tools. Later, through collaboration with NASA, an immersive virtual environment was created to produce high-fidelity images for surgical simulation, but it underestimated the importance of collaboration. The next system, a networked, distributed virtual environment, provided immersion and collaboration, but the immersive paradigm was found to be of a disadvantage and the uniqueness of the framework unwieldy. A virtual model, workbench-style display was then created using a commercial package, but limitations of each were soon apparent. Finally, a specialized display, with an integrated visualization and simulation system is described and evaluated. Lessons learned include: surgical planning is an abstract process unlike surgical simulation; collaboration is important, as is stereo visualization; and that high-resolution preoperative images from standard viewpoints are desirable, but interaction is truly the key to planning.

Communicating bioastronautics research to students, families and the nation.

The National Space Biomedical Research Institute (NSBRI) is supporting the National Aeronautics and Space Administration's (NASA) education mission through a comprehensive Education and Public Outreach Program (EPOP) that communicates the excitement and significance of space biology to schools, families, and lay audiences. The EPOP is comprised of eight academic institutions: Baylor College of Medicine, Massachusetts Institute of Technology, Morehouse School of Medicine, Mount Sinai School of Medicine, Texas A&M University, University of Texas Medical Branch Galveston, Rice University, and the University of Washington. This paper describes the programs and products created by the EPOP to promote space life science education in schools and among the general public. To date, these activities have reached thousands of teachers and students around the US and have been rated very highly.

Increasing student learning through space life sciences education.

Scientists and educators at Baylor College of Medicine are using space life sciences research areas as themes for middle school science and health instructional materials. This paper discusses study findings of the most recent unit, Food and Fitness, which teaches concepts related to energy and nutrition through guided inquiry. Results of a field test involving more than 750 students are reported. Use of the teaching materials resulted in significant knowledge gains by students as measured on a pre/post assessment administered by teachers. In addition, an analysis of the time spent by each teacher on each activity suggested that it is preferable to conduct all of the activities in the unit with students rather than allocating the same total amount of time on just a subset of the activities.

Invited review: gender issues related to spaceflight: a NASA perspective.

This minireview provides an overview of known and potential gender differences in physiological responses to spaceflight. The paper covers cardiovascular and exercise physiology, barophysiology and decompression sickness, renal stone risk, immunology, neurovestibular and sensorimotor function, nutrition, pharmacotherapeutics, and reproduction. Potential health and functional impacts associated with the various physiological changes during spaceflight are discussed, and areas needing additional research are highlighted. Historically, studies of physiological responses to microgravity have not been aimed at examining gender-specific differences in the astronaut population. Insufficient data exist in most of the discipline areas at this time to draw valid conclusions about gender-specific differences in astronauts, in part due to the small ratio of women to men. The only astronaut health issue for which a large enough data set exists to allow valid conclusions to be drawn about gender differences is orthostatic intolerance following shuttle missions, in which women have a significantly higher incidence of presyncope during stand tests than do men. The most common observation across disciplines is that individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders. Individual characteristics usually outweigh gender differences per se.

Life sciences space missions. Overview.

It has been known for many years that weightlessness induces changes in numerous physiological systems: the cardiovascular system declines in both aerobic capacity and orthostatic tolerance; there is a reduction in fluid and electrolyte balance, hematocrit, and certain immune parameters; bone and muscle mass and strength are reduced; various neurological responses include space motion sickness and posture and gate alterations. These responses are caused by the hypokinesia of weightlessness, the cephalic fluid shift, the unloading of the vestibular system, stress, and the altered temporal environment.

Predictions of adult Anopheles albimanus densities in villages based on distances to remotely sensed larval habitats.

Remote sensing is particularly helpful for assessing the location and extent of vegetation formations, such as herbaceous wetlands, that are difficult to examine on the ground. Marshes that are sparsely populated with emergent macrophytes and dense cyanobacterial mats have previously been identified as very productive Anopheles albimanus larval habitats. This type of habitat was detectable on a classified multispectral System Probatoire d'Observation de la Terre image of northern Belize as a mixture of two isoclasses. A similar spectral signature is characteristic for vegetation of river margins consisting of aquatic grasses and water hyacinth, which constitutes another productive larval habitat. Based on the distance between human settlements (sites) of various sizes and the nearest marsh/river exhibiting this particular class combination, we selected two groups of sites: those located closer than 500 m and those located more than 1,500 m from such habitats. Based on previous adult collections near larval habitats, we defined a landing rate of 0.5 mosquitoes/human/min from 6:30 PM to 8:00 PM as the threshold for high (> or = 0.5 mosquitoes/human/min) versus low (< 0.5 mosquitoes/human/min) densities of An. albimanus. Sites located less than 500 m from the habitat were predicted as having values higher than this threshold, while lower values were predicted for sites located greater than 1,500 m from the habitat. Predictions were verified by collections of mosquitoes landing on humans. The predictions were 100% accurate for sites in the > 1,500-m category and 89% accurate for sites in the < 500-m category.

Predictions of malaria vector distribution in Belize based on multispectral satellite data.

Use of multispectral satellite data to predict arthropod-borne disease trouble spots is dependent on clear understandings of environmental factors that determine the presence of disease vectors. A blind test of remote sensing-based predictions for the spatial distribution of a malaria vector, Anopheles pseudopunctipennis, was conducted as a follow-up to two years of studies on vector-environmental relationships in Belize. Four of eight sites that were predicted to be high probability locations for presence of An. pseudopunctipennis were positive and all low probability sites (0 of 12) were negative. The absence of An. pseudopunctipennis at four high probability locations probably reflects the low densities that seem to characterize field populations of this species, i.e., the population densities were below the threshold of our sampling effort. Another important malaria vector, An. darlingi, was also present at all high probability sites and absent at all low probability sites. Anopheles darlingi, like An. pseudopunctipennis, is a riverine species. Prior to these collections at ecologically defined locations, this species was last detected in Belize in 1946.

Physiological adaptations and countermeasures associated with long-duration spaceflights.

Since 1961, there have been more than 165 flights involving several hundred individuals who have remained in a space environment from 15 min to more than a year. In addition, plans exist for humans to explore, colonize, and remain in microgravity for 1000 d or more. This symposium will address the current state of knowledge in select aspects associated with the cardiovascular, fluid and electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The authors will focus on responses, mechanisms, and the appropriate countermeasures to minimize or prevent the physiological and biochemical consequences of a microgravity environment. Since exercise is frequently cited as a generic countermeasure, this topic will be covered in greater detail. Models for simulated microgravity conditions will be discussed in subsequent manuscripts, as will future directions for ground-based research.

Reproduction in the space environment: Part I. Animal reproductive studies.

Mankind's exploration and colonization of the frontier of space will ultimately depend on men's and women's ability to live, work, and reproduce in the space environment. This paper reviews animal studies, from microorganisms to mammals, done in space or under space-simulated conditions, which identify some of the key areas which might interfere with human reproductive physiology and/or embryonic development. Those space environmental factors which impacted almost all species included: microgravity, artificial gravity, radiation, and closed life support systems. These factors may act independently and in combination to produce their effects. To date, there have been no studies which have looked at the entire process of reproduction in any animal species. This type of investigation will be critical in understanding and preventing the problems which will affect human reproduction. Part II will discuss these problems directly as they relate to human physiology.

Reproduction in the space environment: Part II. Concerns for human reproduction.

Long-duration space flight and eventual colonization of our solar system will require successful control of reproductive function and a thorough understanding of factors unique to space flight and their impact on gynecologic and obstetric parameters. Part II of this paper examines the specific environmental factors associated with space flight and the implications for human reproduction. Space environmental hazards discussed include radiation, alteration in atmospheric pressure and breathing gas partial pressures, prolonged toxicological exposure, and microgravity. The effects of countermeasures necessary to reduce cardiovascular deconditioning, calcium loss, muscle wasting, and neurovestibular problems are also considered. In addition, the impact of microgravity on male fertility and gamete quality is explored. Due to current constraints, human pregnancy is now contraindicated for space flight. However, a program to explore effective countermeasures to current constraints and develop the required health care delivery capability for extended-duration space flight is suggested. A program of Earth- and space-based research to provide further answers to reproductive questions is suggested.

Characterization of Anopheles darlingi (Diptera: Culicidae) larval habitats in Belize, Central America.

Surveys for larvae of Anopheles darlingi Root were conducted in April, May, and August 1994 in riverine habitats of central Belize (Cayo and Belize districts). An. darlingi was present during both the dry and wet seasons. Larvae were encountered most frequently in patches of floating debris along river margins. The floating mats were often formed by bamboo hanging over the banks and dense submersed bamboo roots. Larvae were found less frequently in lake margins, small lagoons, and ground pools with submersed roots and patches of floating leaves or vegetation. In addition to their association with floating debris, larvae of An. darlingi were associated positively with shade and submersed plants in riverine environments. Samples from river habitats showed the larvae of Anopheles albimanus Wiedemann to be strongly associated with sun-exposed sites containing green or blue-green algae. Unlike An. darlingi, An. albimanus was an ubiquitous mosquito, the immatures of which occurred in a wide variety of riverine and nonriverine aquatic habitats. Based on published reports and our experience, the association of An. darlingi with river systems was verified, and its distribution in Central America and Mexico was mapped.

Introduction: an overview of gravity sensing, perception, and signal transduction in animals and plants.

The antiquity of biological sensitivity and response to gravity can be traced through the ubiquity of morphology, mechanisms, and cellular events in gravity sensing biological systems in the most diverse species of both plants and animals. Further, when we examine organisms at the cellular level to elucidate the molecular mechanism by which a gravitational signal is transduced into a biochemical response, the distinction between plants and animals becomes blurred.

NASA's Space Life Sciences Training Program.

The Space Life Sciences Training Program (SLSTP) is an intensive, six-week training program held every summer since 1985 at the Kennedy Space Center (KSC). A major goal of the SLSTP is to develop a cadre of qualified scientists and engineers to support future space life sciences and engineering challenges. Hand-picked, undergraduate college students participate in lectures, laboratory sessions, facility tours, and special projects: including work on actual Space Shuttle flight experiments and baseline data collection. At NASA Headquarters (HQ), the SLSTP is jointly sponsored by the Life Sciences Division and the Office of Equal Opportunity Programs: it has been very successful in attracting minority students and women to the fields of space science and engineering. In honor of the International Space Year (ISY), 17 international students participated in this summer's program. An SLSTP Symposium was held in Washington D.C., just prior to the World Space Congress. The Symposium attracted over 150 SLSTP graduates for a day of scientific discussions and briefings concerning educational and employment opportunities within NASA and the aerospace community. Future plans for the SLSTP include expansion to the Johnson Space Center in 1995.

Issues of exploration: human health and wellbeing during a mission to Mars.

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart.

Long-term effects of microgravity and possible countermeasures.

It is well known that long-term exposure to microgravity causes a number of physiological and biochemical changes in humans; among the most significant are: 1) negative calcium balance resulting in the loss of bone; 2) atrophy of antigravity muscles; 3) fluid shifts and decreased plasma volume; and 4) cardiovascular deconditioning that leads to orthostatic intolerance. It is estimated that a mission to Mars may require up to 300 days in a microgravity environment; in the case of an aborted mission, the astronauts may have to remain in reduced gravity for up to three years. Although the Soviet Union has shown that exercise countermeasures appear to be adequate for exposures of up to one year in space, it is questionable whether astronauts could or should have to maintain such regimes for extremely prolonged missions. Therefore, the NASA Life Sciences Division has initiated a program designed to evaluate a number of methods for providing an artificial gravity environment.