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NASA NTRS2010

Ultrasound Imaging of Spine: State of the Art and Utility for Space Flight

Introduction: Ultrasound imaging (sonography) has been increasingly used for both primary diagnosis and monitoring of musculoskeletal injury, including fractures. In certain injuries, sonography has been shown to equal or surpass Magnetic Resonance Imaging in accuracy. Long-term exposure to reduced gravity may be expected to cause physiological and anatomical changes of the musculoskeletal system, which are not fully described or understood. In a limited-resource environment like space flight, sonography will likely remain the only imaging modality; therefore, further attention to its potential is warranted, including its ability to image anatomical deviations as well as irregularities of vertebrae and the spinal column. Methods: A thorough review of literature was conducted on the subject. A multipurpose ultrasound system was used to identify specific vertebrae, intervertebral disks, and other structures of the cervical spine in healthy volunteers, selected to represent various age, gender, and Body Mass Index (BMI) groups. Sonographic views were sought that would parallel radiographic views and signs used in the diagnosis of cervical spine injuries. Results: While using widely accepted radiographic signs of cervical spine injury, this sonographic protocol development effort resulted in successful identification of scanning planes and imaging protocols that could serve as alternatives for radiography. Some of these views are also applicable to diagnosing degenerative disk and bone disease, and other non-traumatic spine pathology. Strong, preliminary correlation has been demonstrated in a number of clinical cases between sonography and other imaging modalities. Conclusion: In the absence of radiography, sonography can be used to diagnose or rule out certain common types of cervical spine conditions including injury. Clinical validation of the findings appears to be realistic and would facilitate establishment of new sonographic protocols for special environments with lacking radiographic capability, such as human space flight.

Sargsyan, Ashot E.↗

NASA NTRS2011

Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P < 0.001) from a linear combination of 5 independent variables: QRS elevation in the frontal plane (p<0.001), a new repolarization parameter QTcorr (p<0.001), mean high frequency QRS amplitude (p=0.009), the variability parameter % VLF of RRV (p=0.021) and the P-wave width (p=0.10). Here, QTcorr represents the correlation between the calculated QT and the measured QT signal. Conclusions: In apparently healthy subjects with normal conventional ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

Schlegel, Todd↗

NASA NTRS2011

Deployment of an Advanced Electrocardiographic Analysis (A-ECG) to Detect Cardiovascular Risk in Career Firefighters

INTRODUCTION Sudden cardiac death is the leading cause of line of duty death among firefighters, accounting for approximately 45% of fatalities annually. Firefighters perform strenuous muscular work while wearing heavy, encapsulating personal protective equipment in high ambient temperatures, under chaotic and emotionally stressful conditions. These factors can precipitate sudden cardiac events like myocardial infarction, serious dysrhythmias, or cerebrovascular accidents in firefighters with underlying cardiovascular disease. Screening for cardiovascular risk factors is recommended but not always followed in this population. PHASER is a project charged with identifying and prioritizing risk factors in emergency responders. We have deployed an advanced ECG (A-ECG) system developed at NASA for improved sensitivity and specificity in the detection of cardiac risk. METHODS Forty-four professional firefighters were recruited to perform comprehensive baseline assessments including tests of aerobic performance and laboratory tests for fasting lipid profiles and glucose. Heart rate and conventional 12-lead ECG were obtained at rest and during incremental treadmill exercise testing (XT). In addition, a 5-min resting 12-lead A-ECG was obtained in a subset of firefighters (n=18) and transmitted over a secure networked system to a physician collaborator at NASA for advanced-ECG analysis. This A-ECG system has been proven, using myocardial perfusion and other imaging, to accurately identify a number of cardiac pathologies including coronary artery disease (CAD), left ventricular hypertrophy, hypertrophic cardiomyopathy, non-ischemic cardiomyopathy, and ischemic cardiomyopathy. RESULTS Subjects mean (SD) age was 43 (8) years, weight 91 (13) kg, and BMI of 28 (3) kg/square meter. Maximum oxygen uptake (VO2max) was 39 (9) ml/kg/min. This compares with the 45th %ile in healthy reference values and a recommended standard of 42 ml/kg/min for firefighters. The metabolic threshold (VO2Theta) above which lactate accumulates was 23 (8) ml/kg/min. The chronotropic index, a measure of cardiovascular strain during XT was 35 (8) /L compared with reference values for men of 40 /L. Total cholesterol, LDL-C and HDL-C were 202 (34),126 (29), and 55 (15) mg/dl, respectively. Fifty-one percent of subjects had .3 cardiovascular risk factors, 2 subjects had resting hypertension (BP.140/90), and 23 had pre-hypertension (.120/80 but <140/90). Seven had exaggerated exercise induced hypertension but only one had ST depression on XT ECG, at least one positive A-ECG score for CAD, and documented CAD based on cardiology referral. While all other subjects, including those with fewer risk factors, higher aerobic fitness, and normal exercise ECGs, were classified as healthy by A-ECG, there was no trend for association between risk factors and any of 20 A-ECG parameters in the grouped data. CONCLUSIONS A-ECG screening correctly identified the individual with CAD although there was no trend for A-ECG parameters to distinguish those with elevated BP or multiple risk factors but normal XT ECG. We have demonstrated that a new technology, advanced-ECG, can be introduced for remote firefighter risk assessment. This simple, time and cost-effective approach to risk identification that can be acquired remotely and transmitted securely can detect individuals potentially at risk for line-of-duty death. Additional research is needed to further document its value.

Dolezal, B. A.↗

NASA NTRS2011

Deployment of an Advanced Electrocardiographic Analysis (A-ECG) to Detect Cardiovascular Risk in Career Firefighters

INTRODUCTION: Sudden cardiac death is the leading cause of line of duty death among firefighters, accounting for approximately 45% of fatalities annually. Firefighters perform strenuous muscular work while wearing heavy, encapsulating personal protective equipment in high ambient temperatures, under chaotic and emotionally stressful conditions. These factors can precipitate sudden cardiac events like myocardial infarction, serious dysrhythmias, or cerebrovascular accidents in firefighters with underlying cardiovascular disease. PURPOSE: The purpose of this study was to deploy and then evaluate the contribution of resting advanced ECG (A-ECG) in addition to other screening tools (family history, lipid profiles, and cardiopulmonary exercise tests, XT) in assessment of an individual fs cardiac risk profile. METHODS: Forty-four career firefighters were recruited to perform comprehensive baseline assessments including tests of aerobic performance, fasting lipids and glucose. Five-min resting 12-lead A-ECGs were obtained in a subset of firefighters (n=21) and transmitted over a secure networked system to a NASA physician collaborator. Using myocardial perfusion and other imaging as the gold standard, A-ECG scoring has been proven useful in accurately identifying a number of cardiac pathologies including coronary artery disease (CAD), left ventricular hypertrophy, hypertrophic cardiomyopathy, and non-ischemic and ischemic cardiomyopathy. RESULTS: Subjects f mean (SD) age was 43 (8) years, weight 91 (13) kg, and BMI 28 (3) kg/m2. Fifty-one percent of subjects had .3 cardiovascular risk factors. One subject had ST depression on XT ECG, at least one positive A-ECG score for CAD, and documented CAD based on cardiology referral. While all other subjects, including those with fewer risk factors, higher aerobic fitness, and normal exercise ECGs, were classified as healthy by A-ECG, there was no trend for association between risk factors and any of 20 A-ECG parameters in the grouped data.

Dolezal, B. A.↗

NASA NTRS2011

A Data Mining Project to Identify Cardiovascular Related Factors That May Contribute to Changes in Visual Acuity Within the US Astronaut Corps

Many of the cardiovascular-related adaptations that occur in the microgravity environment are due, in part, to a well-characterized cephalad-fluid shift that is evidenced by facial edema and decreased lower limb circumference. It is believed that most of these alterations occur as a compensatory response necessary to maintain a "normal" blood pressure and cardiac output while in space. However, data from both flight and analog research suggest that in some instances these microgravity-induced alterations may contribute to cardiovascular-related pathologies. Most concerning is the potential relation between the vision disturbances experienced by some long duration crewmembers and changes in cerebral blood flow and intra-ocular pressure. The purpose of this project was to identify cardiovascular measures that may potentially distinguish individuals at risk for visual disturbances after long duration space flight. Toward this goal, we constructed a dataset from Medical Operation tilt/stand test evaluations pre- (days L-15-L-5) and immediate post-flight (day R+0) on 20 (3 females, 17 males). We restricted our evaluation to only crewmembers who participated in both shuttle and space station missions. Data analysis was performed using both descriptive and analytical methods (Stata 11.2, College Station, TX) and are presented as means +/- 95% CI. Crewmembers averaged 5207 (3447 - 8934) flight hours across both long (MIR-23 through Expedition16) and short (STS-27 through STS-101) duration missions between 1988 and 2008. The mean age of the crew at the time of their most recent shuttle flight was 41 (34-44) compared to 47 (40-54) years during their time on station. In order to focus our analysis (we did not have codes to separate out subjects by symptomotology) , we performed a visual inspection of each cardiovascular measures captured during testing and plotted them against stand time, pre- to post-flight, and between mission duration. It was found that pulse pressure most clearly differentiated the two mission types. Statistical analysis confirmed that pulse pressure was significantly higher before [45.6; (42.1 to 49.1)] and after [50.7; (46.9 to 54.6)] time on station compared with their most recent shuttle flight [31.6 (27.8 to 35.4), and 32.2 (28.3 to 36.0) respectively] even after correcting differences in age and cumulative number of mission hours. Without knowing the identity of which long duration crewmembers demonstrated visual changes, we were limited to examining whether certain crew regulate components of pulse pressure, systolic and diastolic blood pressure, differently due to microgravity exposure. To that end, we stratified crew into tertiles based on either their pre-flight measure of systolic or diastolic blood pressure. Those crew in the highest tertile for both systolic (lower tertile (n=8; 103-111), middle tertile (n=7; 113-121), and upper tertile (n=5; 125-136) and diastolic blood pressure (lower tertile (n=8; 58-64), middle tertile (n=7; 67-73), and upper tertile (n=5; 75-81) demonstrated less variability in pulse pressure between R+0 and L-10 (Figure 2). Interestingly, those crewmembers with the highest resting systolic blood pressure demonstrated either no change or in some instances an increase in total peripheral resistance, where those in the lower tertiles had lower values of total peripheral resistance compared to pre-flight levels. In this study, it was found that crewmembers in the highest tertile for both systolic and diastolic blood pressure demonstrated less variability in pulse pressure and that the decrease in variability was due in part to lower levels of compliance as indicated by similar or higher levels of total peripheral resistance after compared with before flight levels. Whether there is a relation between blood pressure regulation and total peripheral resistance in crew presenting with negative changes in visual acuity remains unknown.

Westby, Christian M.↗

NASA NTRS2011

Super Dwarf Wheat for Growth in Confined Spaces

USU-Perigee is a dwarf red spring wheat that is a hybrid of a high-yield early tall wheat (USU-Apogee) and a low-yield, extremely short wheat that has poor agronomic characteristics. USU-Perigee was selected for its extremely short height (.0.3 m) and high yield . characteristics that make it suitable for growth in confined spaces in controlled environments. Other desirable characteristics include rapid development and resistance to a leaf-tip necrosis, associated with calcium deficiency, that occurs in other wheat cultivars under rapid-growth conditions (particularly, continuous light). Heads emerge after only 21 days of growth in continuous light at a constant temperature of 25 C. In tests, USU-Perigee was found to outyield other full dwarf (defined as <0.4 m tall) wheat cultivars: The yield advantage at a constant temperature of 23 C was found to be about 30 percent. Originally intended as a candidate food crop to be grown aboard spacecraft on long missions, this cultivar could also be grown in terrestrial growth chambers and could be useful for plant-physiology and -pathology studies.

Bugbee, Bruce↗

NASA NTRS2011

Principles, Techniques, and Applications of Tissue Microfluidics

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called tissue microfluidics because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets. The proposed principles represent a paradigm shift in microfluidic technology in three important ways: Microfluidic devices are to be directly integrated with, onto, or around tissue samples, in contrast to the conventional method of off-chip sample extraction followed by sample insertion in microfluidic devices. Architectural and operational principles of microfluidic devices are to be subordinated to suit specific tissue structure and needs, in contrast to the conventional method of building devices according to fluidic function alone and without regard to tissue structure. Sample acquisition from tissue is to be performed on-chip and is to be integrated with the diagnostic measurement within the same device, in contrast to the conventional method of off-chip sample prep and subsequent insertion into a diagnostic device. A more advanced form of tissue integration with microfluidics is tissue encapsulation, wherein the sample is completely encapsulated within a microfluidic device, to allow for full surface access. The immediate applications of these approaches lie with diagnostics of tissue slices and biopsy samples e.g. for cancer but the approaches would also be very useful in comparative genomics and other areas of fundamental research involving heterogeneous tissue samples.

Wade, Lawrence A.↗

NASA NTRS2011

Numerical Implementation of a Multiple-ISV Thermodynamically-Based Work Potential Theory for Modeling Progressive Damage and Failure in Fiber-Reinforced Laminates

A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Damage is considered to be the effect of any structural changes in a material that manifest as pre-peak non-linearity in the stress versus strain response. Conversely, failure is taken to be the effect of the evolution of any mechanisms that results in post-peak strain softening. It is assumed that matrix microdamage is the dominant damage mechanism in continuous fiber-reinforced polymer matrix laminates, and its evolution is controlled with a single ISV. Three additional ISVs are introduced to account for failure due to mode I transverse cracking, mode II transverse cracking, and mode I axial failure. Typically, failure evolution (i.e., post-peak strain softening) results in pathologically mesh dependent solutions within a finite element method (FEM) setting. Therefore, consistent character element lengths are introduced into the formulation of the evolution of the three failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs is derived. The theory is implemented into commercial FEM software. Objectivity of total energy dissipated during the failure process, with regards to refinements in the FEM mesh, is demonstrated. The model is also verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared to the experiments.

Pineda, Evan J.↗

NASA NTRS2011

Radiation Protection Using Single-Wall Carbon Nanotube Derivatives

This invention is a means of radiation protection, or cellular oxidative stress mitigation, via a sequence of quenching radical species using nano-engineered scaffolds, specifically single-wall carbon nanotubes (SWNTs) and their derivatives. The material can be used as a means of radiation protection by reducing the number of free radicals within, or nearby, organelles, cells, tissue, organs, or living organisms, thereby reducing the risk of damage to DNA and other cellular components (i.e., RNA, mitochondria, membranes, etc.) that can lead to chronic and/or acute pathologies, including but not limited to cancer, cardiovascular disease, immuno-suppression, and disorders of the central nervous system. In addition, this innovation could be used as a prophylactic or antidote for accidental radiation exposure, during high-altitude or space travel where exposure to radiation is anticipated, or to protect from exposure from deliberate terrorist or wartime use of radiation- containing weapons.

Tour, James M.↗

NASA NTRS2011

Principles, Techniques, and Applications of Tissue Microfluidics

Wade, Lawrence A.↗

NASA NTRS2012

Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment.

Westby, Christian M.↗

NASA NTRS2012

Physico-Chemical-Managed Killing of Penicillin-Resistant Static and Growing Gram-Positive and Gram-Negative Vegetative Bacteria

Systems and methods for the use of compounds from the Hofmeister series coupled with specific pH and temperature to provide rapid physico-chemical-managed killing of penicillin-resistant static and growing Gram-positive and Gram-negative vegetative bacteria. The systems and methods represent the more general physico-chemical enhancement of susceptibility for a wide range of pathological macromolecular targets to clinical management by establishing the reactivity of those targets to topically applied drugs or anti-toxins.

Richmond, Robert Chaffee↗

NASA NTRS2012

A Thermodynamically-Based Mesh Objective Work Potential Theory for Predicting Intralaminar Progressive Damage and Failure in Fiber-Reinforced Laminates

Pineda, Evan J.↗

NASA NTRS2012

Spaceflight Effects and Molecular Responses in the Mouse Eye: Observations after NASA Shuttle Mission STS-133

Background: Human space exploration implies a combination of stressors including microgravityinduced cephalad fluid shift and radiation exposure. Ocular changes in astronauts leading to visual impairment are of occupational health relevance. The effect of this complex environment on ocular morphology and function is poorly understood. Material and Methods: Mice were assigned to a Flight (FLT) group flown on shuttle mission STS133, Animal Enclosure Module (AEM), or vivarium (VIV) ground controls. Eyes were collected at 1, 5 and 7 days after landing, and were fixed for histological sectioning. The contralateral eye was used for gene expression profiling by qRT-PCR. Routine histology and immunohistochemistry using 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, glial fibrillary acidic protein (GFAP) and beta-amyloid were used to study the eyes. Results and Conclusions: 8-OHdG and caspase-3 immunoreactivity was increased in the retina in FLT samples at return from flight (R+1) compared to ground controls, and decreased at day 7 (R+7), suggesting an increase in oxidative stress and cell apoptosis. FLT mice showed evidence of retinal pigment epithelium (RPE) apoptosis possibly secondary to oxidative damage. Although attenuation of RPE has been related to retinal choroidal folds in astronauts, it is yet to be determined whether or not increased RPE apoptosis may contribute to the formation of choroidal folds or may increase the risk for other retinal pathologies, such as AMD. beta-amyloid was seen in the nerve fibers at the post-laminar region of the optic nerve in the flight samples (R+7). Deposition of beta-amyloid has a strong correlation with mechanical trauma. The coexpression of GFAP in astrocytes and oligodentrocytes in these same areas supports the possible mechanical origin probably secondary to intracranial pressure that is transmitted into the nerve, as a result of an increase in venous pressure associated to microgravity-induced cephalic fluid shift. However, there is the need to further investigate the nature of the changes through additional experimental work. Gene expression of oxidative and cellular stress response genes was unregulated in the retina of FLT samples upon landing followed by lower levels by R+7. These results suggest that reversible molecular damage occurs in the retina of mice exposed to spaceflight and that protective cellular and molecular pathways are induced in the retina in response to these changes.

ProsperoPonce, Claudia Maria↗

NASA NTRS2012

Orbital and Intracranial Effects of Microgravity: 3T MRI Findings

Goals and Objectives of this presentation are: 1. To briefly describe a newly discovered clinical entity related to space flight. 2. To describe normal anatomy and pathologic changes of the optic nerve, posterior globe, optic nerve sheath and pituitary gland related to exposure to microgravity. 3. To correlate imaging findings with known signs of intracranial hypertension.

Kramer, L. A.↗

NASA NTRS2012

An Integrated Biomechanical Model for Microgravity-Induced Visual Impairment

When gravitational unloading occurs upon entry to space, astronauts experience a major shift in the distribution of their bodily fluids, with a net headward movement. Measurements have shown that intraocular pressure spikes, and there is a strong suspicion that intracranial pressure also rises. Some astronauts in both short- and long-duration spaceflight develop visual acuity changes, which may or may not reverse upon return to earth gravity. To date, of the 36 U.S. astronauts who have participated in long-duration space missions on the International Space Station, 15 crew members have developed minor to severe visual decrements and anatomical changes. These ophthalmic changes include hyperopic shift, optic nerve distension, optic disc edema, globe flattening, choroidal folds, and elevated cerebrospinal fluid pressure. In order to understand the physical mechanisms behind these phenomena, NASA is developing an integrated model that appropriately captures whole-body fluids transport through lumped-parameter models for the cerebrospinal and cardiovascular systems. This data feeds into a finite element model for the ocular globe and retrobulbar subarachnoid space through time-dependent boundary conditions. Although tissue models and finite element representations of the corneo-scleral shell, retina, choroid and optic nerve head have been integrated to study pathological conditions such as glaucoma, the retrobulbar subarachnoid space behind the eye has received much less attention. This presentation will describe the development and scientific foundation of our holistic model.

Nelson, Emily S.↗

NASA NTRS2013

Clinical Practice Guideline for Vitamin D

Vitamin D and its metabolites have clinical significance because they play a critical function in calcium homeostasis and bone metabolism. Although not all of the pathologic mechanisms have been adequately described, vitamin D insufficiency and deficiency, as measured by low levels of 25-OH vitamin D, are associated with a variety of clinical conditions including osteoporosis, falls and fractures in the elderly, decreased immune function, bone pain, and possibly colon cancer and cardiovascular health.2 Apart from inadequate dietary intake, patients may present with low levels of vitamin D if they receive inadequate sunlight. The astronaut population is potentially vulnerable to low levels of vitamin D for several reasons. Firstly, they may train for long periods in Star City, Russia, which by virtue of its northern latitude receives less sunlight in winter months. Secondly, astronauts are deprived of sunlight while aboard the International Space Station (ISS). In addition, ISS crew members are exposed to microgravity for prolonged durations and are likely to develop low bone mineral density despite the use of countermeasures. Therefore, closely monitoring and maintaining adequate vitamin D levels is important for the astronaut corps.

Tarver, William J.↗

NASA NTRS2014

Persistent Expression Changes of Fibrosis-Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1‐2% of very fine respirable dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust‐induced changes of the expression of fibrosis‐related genes, and to identify specific signaling pathways involved in lunar dustinduced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose‐only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 milligrams per cubic meters of lunar dust. Five rats per group were euthanized at 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The bronchoalveolar lavage fluid (BALF) was collected by lavaging with phosphate‐buffered saline (PBS). A zymosan‐induced luminolbased chemiluminescence assay was used to assess the activity of BAL cells. The lavaged lung tissue was snap frozen in LN2 and total RNA was isolated using the Qigen RNeasy kit. The expression of 84 fibrosisrelated genes were analyzed using the RT2 Profiler PCR Array technique. The expression of 18 genes of interest were further measured using real‐time PCR technique in all the samples. 10 out of 18 genes of interest showed persistently significant expression changes in the local lung tissue exposed to lunar dust, indicating a prolonged proinflammatory response. The expressions of several of these genes were dose‐ and time‐dependent and were significantly correlated with other pathological parameters. The potential signaling pathways and upstream regulators were further analyzed using IPA pathway analysis tool based on the gene expression data. The data presented in this study, for the first time, explore the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust‐induced toxicity in humans on earth.

Zhang, Ye↗