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NASA NTRS2002

Semicarbazide-sensitive amine oxidase and extracellular matrix deposition by smooth-muscle cells

We have recently reported in vivo disruption of collagen and elastin architecture within blood vessel walls resulting from the selective inhibition of the enzyme semicarbazide-sensitive amine oxidase (SSAO). This study further investigates the effects of SSAO inhibition on extracellular matrix deposition by smooth-muscle cells (SMCs) cultured from neonatal rat hearts. SMCs were characterized, SSAO activity was measured, and soluble and insoluble collagen and elastin in the extracellular matrix (ECM) were quantified. Cultured neonatal rat heart SMC exhibited a monotypic synthetic phenotype that likely represents a myofibroblast. Detectable levels of SSAO activity present throughout 30-d culture peaked at 7-14 d, coinciding with the production of ECM. The addition of enzyme inhibitors and alternate SSAO substrates (benzylamine) produced varied and, in some cases, marked changes in SSAO activity as well as in the composition of mature and soluble matrix components. Similar to our previous in vivo findings, in vitro SSAO inhibition produced aberrations in collagen and elastin deposition by heart SMC. Because changes in SSAO activity are associated with cardiovascular pathologic states, this enzyme may play a protective or modulating role by regulating ECM production during pathologic insult.

Allylamine/administration & dosage/analogs & deriv↗

NASA NTRS2000

Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study

BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard for evaluation of the left atrium and the left atrial appendage (LAA) for the presence of thrombi. Anticoagulation is conventionally used for patients with atrial fibrillation to prevent embolization of atrial thrombi. The mechanism of benefit and effectiveness of thrombi resolution with anticoagulation is not well defined. METHODS AND RESULTS: We used a TEE database of 9058 consecutive studies performed between January 1996 and November 1998 to identify all patients with thrombi reported in the left atrium and/or LAA. One hundred seventy-four patients with thrombi in the left atrial cavity (LAC) and LAA were identified (1.9% of transesophageal studies performed). The incidence of LAA thrombi was 6.6 times higher than LAC thrombi (151 vs 23, respectively). Almost all LAC thrombi were visualized on transthoracic echocardiography (90.5%). Mitral valve pathology was associated with LAC location of thrombi (P <.0001), whereas atrial fibrillation or flutter was present in most patients with LAA location of thrombi. Anticoagulation of 47 +/- 18 days was associated with thrombus resolution in 80.1% of the patients on follow-up TEE. Further anticoagulation resulted in limited additional benefit. CONCLUSIONS: LAC thrombi are rare and are usually associated with mitral valve pathology. Transthoracic echocardiography is effective in identifying these thrombi. LAA thrombi occur predominantly in patients with atrial fibrillation or flutter. Short-term anticoagulation achieves a high rate of resolution of LAA and LAC thrombi but does not obviate the need for follow-up TEE.

NASA Discipline Cardiopulmonary↗

NASA NTRS2000

Dynamic markers of altered gait rhythm in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a disorder marked by loss of motoneurons. We hypothesized that subjects with ALS would have an altered gait rhythm, with an increase in both the magnitude of the stride-to-stride fluctuations and perturbations in the fluctuation dynamics. To test for this locomotor instability, we quantitatively compared the gait rhythm of subjects with ALS with that of normal controls and with that of subjects with Parkinson's disease (PD) and Huntington's disease (HD), pathologies of the basal ganglia. Subjects walked for 5 min at their usual pace wearing an ankle-worn recorder that enabled determination of the duration of each stride and of stride-to-stride fluctuations. We found that the gait of patients with ALS is less steady and more temporally disorganized compared with that of healthy controls. In addition, advanced ALS, HD, and PD were associated with certain common, as well as apparently distinct, features of altered stride dynamics. Thus stride-to-stride control of gait rhythm is apparently compromised with ALS. Moreover, a matrix of markers based on gait dynamics may be useful in characterizing certain pathologies of motor control and, possibly, in quantitatively monitoring disease progression and evaluating therapeutic interventions.

NASA Program Biomedical Research and Countermeasur↗

NASA NTRS1997

Atypical form of Alzheimer's disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways

In recent years, the existence of visual variants of Alzheimer's disease characterized by atypical clinical presentation at onset has been increasingly recognized. In many of these cases post-mortem neuropathological assessment revealed that correlations could be established between clinical symptoms and the distribution of neurodegenerative lesions. We have analyzed a series of Alzheimer's disease patients presenting with prominent visual symptomatology as a cardinal sign of the disease. In these cases, a shift in the distribution of pathological lesions was observed such that the primary visual areas and certain visual association areas within the occipito-parieto-temporal junction and posterior cingulate cortex had very high densities of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in Alzheimer's disease. Previous quantitative analyses have demonstrated that in Alzheimer's disease, primary sensory and motor cortical areas are less damaged than the multimodal association areas of the frontal and temporal lobes, as indicated by the laminar and regional distribution patterns of neurofibrillary tangles and senile plaques. The distribution of pathological lesions in the cerebral cortex of Alzheimer's disease cases with visual symptomatology revealed that specific visual association pathways were disrupted, whereas these particular connections are likely to be affected to a less severe degree in the more common form of Alzheimer's disease. These data suggest that in some cases with visual variants of Alzheimer's disease, the neurological symptomatology may be related to the loss of certain components of the cortical visual pathways, as reflected by the particular distribution of the neuropathological markers of the disease.

Review↗

NASA NTRS1996

Redox-mediated activation of latent transforming growth factor-beta 1

Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that orchestrates response to injury via ubiquitous cell surface receptors. The biological activity of TGF beta is restrained by its secretion as a latent complex (LTGF beta) such that activation determines the extent of TGF beta activity during physiological and pathological events. TGF beta action has been implicated in a variety of reactive oxygen-mediated tissue processes, particularly inflammation, and in pathologies such as reperfusion injury, rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly activated after in vivo radiation exposure, which also generates reactive oxygen species (ROS). In the present studies, the potential for redox-mediated LTGF beta activation was investigated using a cell-free system in which ROS were generated in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction. Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26% activation compared with that elicited by standard thermal activation. Metal-catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta activation that matched or exceeded thermal activation. The efficiency of ascorbate activation depended on ascorbate concentrations and the presence of transition metal ions. We postulate that oxidation of specific amino acids in the latency-conferring peptide leads to a conformation change in the latent complex that allows release of TGF beta. Oxidative activation offers a novel route for the involvement of TGF beta in tissue processes in which ROS are implicated and endows LTGF beta with the ability to act as a sensor of oxidative stress and, by releasing TGF beta, to function as a signal for orchestrating the response of multiple cell types. LTGF beta redox sensitivity is presumably directed toward recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta activation that can be deleterious during disease mechanisms involving chronic ROS production.

Non-NASA Center↗

NASA NTRS2001

Computer Model Used to Help Customize Medicine

Dr. Radhakrishnan, a researcher at the NASA Glenn Research Center, in collaboration with biomedical researchers at the Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital, is developing computational models of human physiology that quantitate metabolism and its regulation, in both healthy and pathological states. These models can help predict the effects of stresses or interventions, such as drug therapies, and contribute to the development of customized medicine. Customized medical treatment protocols can give more comprehensive evaluations and lead to more specific and effective treatments for patients, reducing treatment time and cost. Commercial applications of this research may help the pharmaceutical industry identify therapeutic needs and predict drug-drug interactions. Researchers will be able to study human metabolic reactions to particular treatments while in different environments as well as establish more definite blood metabolite concentration ranges in normal and pathological states. These computational models may help NASA provide the background for developing strategies to monitor and safeguard the health of astronauts and civilians in space stations and colonies. They may also help to develop countermeasures that ameliorate the effects of both acute and chronic space exposure.

Stauber, Laurel J.↗

NASA NTRS2007

New and Improved T-wave Morphology Parameters to Differentiate Healthy Individuals from those with Cardiomyopathy and Coronary Artery Disease

We investigated the ability of several known as well as new ECG repolarization parameters to differentiate healthy individuals from patients with obstructive coronary artery disease (CAD) and cardiomyopathy (CM). Advanced high-fidelity 12-lead ECG tests (approx. 5-min supine) were first performed on a "training set" of 99 individuals: 33 with ischemic or dilated CM and low ejection fraction (EF less than 40%); 33 with catheterization-proven obstructive CAD but normal EF; and 33 age-/gender-matched healthy controls. The following multiple parameters of T-wave morphology (TWM) were derived via signal averaging and singular value decomposition (SVD, which yields 8 eigenvalues, rho(sub 1) greater than rho(sub 2)...greater than rho(sub 8) and studied for their retrospective accuracy in detecting underlying disease: 1) Principal component analysis ratio of the T wave (T-PCA) = 100*rho(sub 2)/rho(sub 1); 2) Relative T-wave residuum (rTWR) = 100* SIGMA (rho(sub 4)(sup 2) +...+ rho(sub 8)(sup 2)); 3) Modified complexity ratio of the T wave (T-mCR) = 100*SIGMA(rho(sub 3)(sup 2) +...+rho(sb 8) (sup 2)); and 4) Normalized 3-dimensional volume of the T wave (nTV) = 100*(rho(sub 2)*rho(sub 3)/rho(sub 1)(sup 2). All TWM parameters significantly differentiated CAD from controls (p less than 0.0001), and also CM from controls (p less than 0.0001). Retrospective areas under the ROC curve were 0.77, 0.81, 0.82, and 0.83 (CAD vs. controls) and 0.93, 0.89, 0.95 and 0.96 (CM vs. controls) for T-PCA, rTWR, T-mCR and nTV respectively. The newer TWM parameters (T-mCR and nTV) thus outperformed the more established parameters (T-PCA and rTWR), presumably by putting a greater emphasis on the third T-wave eigenvalue, which in most healthy subjects has little energy compared to the first two eigenvalues. Subsequent prospective analyses have also yielded similar results, such that we conclude that diagnostic differentiation of pathology from non-pathology may be especially aided by detecting the transference of energy from the first and second T-wave eigenvalues into the third T-wave eigenvalue.

Greco, E. C.↗

NASA NTRS2009

Towards an "All Speed" Unstructured Upwind Scheme

In the authors previous studies [1], a time-accurate, upwind finite volume method (ETAU scheme) for computing compressible flows on unstructured grids was proposed. The scheme is second order accurate in space and time and yields high resolution in the presence of discontinuities. The scheme features a multidimensional limiter and multidimensional numerical dissipation. These help to stabilize the numerical process and to overcome the annoying pathological behaviors of upwind schemes. In the present paper, it will be further shown that such multidimensional treatments also lead to a nearly all-speed or Mach number insensitive upwind scheme. For flows at very high Mach number, e.g., 10, local numerical instabilities or the pathological behaviors are suppressed, while for flows at very low Mach number, e.g., 0.02, computation can be directly carried out without invoking preconditioning. For flows in different Mach number regimes, i.e., low, medium, and high Mach numbers, one only needs to adjust one or two parameters in the scheme. Several examples with low and high Mach numbers are demonstrated in this paper. Thus, the ETAU scheme is applicable to a broad spectrum of flow regimes ranging from high supersonic to low subsonic, appropriate for both CFD (computational fluid dynamics) and CAA (computational aeroacoustics).

Loh, Ching Y.↗

NASA NTRS2006

Noninvasive Diagnosis of Coronary Artery Disease Using 12-Lead High-Frequency Electrocardiograms

A noninvasive, sensitive method of diagnosing certain pathological conditions of the human heart involves computational processing of digitized electrocardiographic (ECG) signals acquired from a patient at all 12 conventional ECG electrode positions. In the processing, attention is focused on low-amplitude, high-frequency components of those portions of the ECG signals known in the art as QRS complexes. The unique contribution of this method lies in the utilization of signal features and combinations of signal features from various combinations of electrode positions, not reported previously, that have been found to be helpful in diagnosing coronary artery disease and such related pathological conditions as myocardial ischemia, myocardial infarction, and congestive heart failure. The electronic hardware and software used to acquire the QRS complexes and perform some preliminary analyses of their high-frequency components were summarized in Real-Time, High-Frequency QRS Electrocardiograph (MSC- 23154), NASA Tech Briefs, Vol. 27, No. 7 (July 2003), pp. 26-28. To recapitulate, signals from standard electrocardiograph electrodes are preamplified, then digitized at a sampling rate of 1,000 Hz, then analyzed by the software that detects R waves and QRS complexes and analyzes them from several perspectives. The software includes provisions for averaging signals over multiple beats and for special-purpose nonrecursive digital filters with specific low- and high-frequency cutoffs. These filters, applied to the averaged signal, effect a band-pass operation in the frequency range from 150 to 250 Hz. The output of the bandpass filter is the desired high-frequency QRS signal. Further processing is then performed in real time to obtain the beat-to-beat root mean square (RMS) voltage amplitude of the filtered signal, certain variations of the RMS voltage, and such standard measures as the heart rate and R-R interval at any given time. A key signal feature analyzed in the present method is the presence versus the absence of reduced-amplitude zones (RAZs). In terms that must be simplified for the sake of brevity, an RAZ comprises several cycles of a high-frequency QRS signal during which the amplitude of the high-frequency oscillation in a portion of the signal is abnormally low (see figure). A given signal sample exhibiting an interval of reduced amplitude may or may not be classified as an RAZ, depending on quantitative criteria regarding peaks and troughs within the reduced-amplitude portion of the high-frequency QRS signal. This analysis is performed in all 12 leads in real time.

Schlegel, Todd T.↗

NASA NTRS2003

Impact Mediated Loading Cytoplasmic Loading of Macromolecules into Adherent Cells

The advent of modern molecular biology, including the development of gene array technologies, has resulted in an explosion of information concerning the specific genes activated during normal cellular development, as well as those associated with a variety of pathological conditions. These techniques have served as a highly efficient, broacI.-based screening approach for those specific genes involved. in regulating normal cellular physiology and identifying candidate genes directly associated with the etiology of specific disease states. However, this approach provides information at the transcriptional' level only and does not necessarily indicate . that the gene in question is in fact translated i~to a protein, or whether or not post-translational modification of the protein occurs. The critical importance of post-translational modification (i.e. phosphorylation, glycosylation, sialyation, etc.) to protein function has been recognized with regard to a number of proteins involved in a variety of important disease states. For example, altered glycosylation of beta-amyloid precursor protein results in an increase in the amount of beta-amyloid peptide generated and hence secreted as insoluble extracellular amyloid deposits (Georgopoulou, McLaughlin et al. 2001; Walter, Fluhrer et al. 2001), a pathological hal1~nark of Alzheimer's disease. Abnormal phosphoryla~ion of synapsin I has been linked to alterations in synaptic vesicle trafficking leading to defective neurotransmission in Huntington's disease (Lievens, Woodman et al. 2002). Altered phosphorylation of the TAU protein involved in microtubule function has been linked to a number of neurodegenative diseases such as Alzheimer's disease (Billingsley and Kincaid 1997; Sanchez, Alvarez-T~llada et a1. 2001). Aberrant siaIyation of cell/I surface antigens has been detected in a number of different tumor cell types and has been linked to the acquisition of a neoplastic phenotype (Sell 1990), while improper' sia1yation of sodium channels in cardiac tissue has been linked to heart failure (Ufret-Vincenty, Baro et al. 2001; Fozzard and Kyle 2002).

Clarke, Mark S. F.↗

NASA NTRS2004

Solution Preserves Nucleic Acids in Body-Fluid Specimens

A solution has been formulated to preserve deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in specimens of blood, saliva, and other bodily fluids. Specimens of this type are collected for diagnostic molecular pathology, which is becoming the method of choice for diagnosis of many diseases. The solution makes it possible to store such specimens at room temperature, without risk of decomposition, for subsequent analysis in a laboratory that could be remote from the sampling location. Thus, the solution could be a means to bring the benefits of diagnostic molecular pathology to geographic regions where refrigeration equipment and diagnostic laboratories are not available. The table lists the ingredients of the solution. The functions of the ingredients are the following: EDTA chelates divalent cations that are necessary cofactors for nuclease activity. In so doing, it functionally removes these cations and thereby retards the action of nucleases. EDTA also stabilizes the DNA helix. Tris serves as a buffering agent, which is needed because minor contaminants in an unbuffered solution can exert pronounced effects on pH and thereby cause spontaneous degradation of DNA. SDS is an ionic detergent that inhibits ribonuclease activity. SDS has been used in some lysis buffers and as a storage buffer for RNA after purification. The use of the solution is straightforward. For example, a sample of saliva is collected by placing a cotton roll around in the subject's mouth until it becomes saturated, then the cotton is placed in a collection tube. Next, 1.5 mL of the solution are injected directly into the cotton and the tube is capped for storage at room temperature. The effectiveness of the solution has been demonstrated in tests on specimens of saliva containing herpes simplex virus. In the tests, the viral DNA, as amplified by polymerase chain reaction, was detected even after storage for 120 days.

Pierson, Duane L.↗

NASA NTRS2013

Computational Modeling of Cephalad Fluid Shift for Application to Microgravity-Induced Visual Impairment

An improved understanding of spaceflight-induced ocular pathology, including the loss of visual acuity, globe flattening, optic disk edema and distension of the optic nerve and optic nerve sheath, is of keen interest to space medicine. Cephalad fluid shift causes a profoundly altered distribution of fluid within the compartments of the head and body, and may indirectly generate phenomena that are biomechanically relevant to visual function, such as choroidal engorgement, compromised drainage of blood and cerebrospinal fluid (CSF), and altered translaminar pressure gradient posterior to the eye. The experimental body of evidence with respect to the consequences of fluid shift has not yet been able to provide a definitive picture of the sequence of events. On earth, elevated intracranial pressure (ICP) is associated with idiopathic intracranial hypertension (IIH), which can produce ocular pathologies that look similar to those seen in some astronauts returning from long-duration flight. However, the clinically observable features of the Visual Impairment and Intracranial Pressure (VIIP) syndrome in space and IIH on earth are not entirely consistent. Moreover, there are at present no experimental measurements of ICP in microgravity. By its very nature, physiological measurements in spaceflight are sparse, and the space environment does not lend itself to well-controlled experiments. In the absence of such data, numerical modeling can play a role in the investigation of biomechanical causal pathways that are suspected of involvement in VIIP. In this work, we describe the conceptual framework for modeling the altered compartmental fluid distribution that represents an equilibrium fluid distribution resulting from the loss of hydrostatic pressure gradient.

Nelson, Emily S.↗

NASA NTRS2014

Validity and Reliability of Dynamic Visual Acuity (DVA) Measurement During Walking

DVA is primarily subserved by the vestibulo‐ocular reflex mechanism. Individuals with vestibular hypofunction commonly experience highly debilitating illusory movement or blurring of visual images during daily activities possibly, due to impaired DVA. Even without pathologies, gradual age‐related morphological deterioration is evident in all components of the vestibular system. We examined the construct validity to detect age‐related differences and test‐retest reliability of DVA measurements performed during walking. METHODS: Healthy adults were recruited into 3 groups: 1. young (20‐39years, n=18), 2. middle‐aged (40‐59years, n=14), and 3. older adults (60‐80years, n=15). Randomly selected seven participants from each group (n=21) participated in retesting. Participants were excluded if they had a history of vestibular or neuromuscular pathologies, dizziness/vertigo or >1 falls in the past year. Older persons with MMSE scores <29/30 were excluded to minimize cognitive errors. Participants' age, height, weight and normal walking speed were recorded. The binocular DVA was measured while walking on a treadmill at 0.8 m/s, 1.0 m/s and 1.2 m/s speeds. The walking speeds chosen represent a range of slow to moderate walking speeds for adult life span in participants who have no current mobility problems. The monitor that displayed Landolt 'C' optotypes was placed at 50 cm from the eyes for nearDVA (primary compensation by otolith organs) and at 3.0 m for farDVA (primary compensation by semicircular canals). A mixed factor ANOVA (age group x speed) was performed separately for the Near and FarDVA for detecting group differences. Intraclass correlation coefficients (ICCs) were calculated for each condition to determine test‐retest reliability. RESULTS: The three age groups were not different in their height, weight and normal walking speed (p>0.05). The post hoc analyses for DVA measurements demonstrated that each group was significantly different from the other two groups for Near as well as FarDVA (p<0.001‐p=0.031). The effect of speed was significant for both NearDVA (p=0.012) and FarDVA (p=0.014), however, there was no age group x speed interaction (FarDVA p=0.607, NearDVA p=0.343). The ICCs for Near and FarDVA ranged between 0.85‐ 0.88 and 0.71‐0.87, respectively. CONCLUSIONS: Differences in DVA between the three age groups were detected by using both Near and FarDVA protocols irrespective of the walking speed. Therefore, age group‐specific reference values should be used for detecting malfunction. Further, consistency in walking speed is critical for comparing between studies. NearDVA at all walking speeds and FarDVA at the speed of 1.2 m/s demonstrated excellent testretest reliability. FarDVA at 0.8 m/s and 1.0 m/s demonstrated good test‐retest reliability (ICCs 0.71 and 0.77, respectively).

Deshpande, Nandini↗

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 reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle 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 through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores 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 to humans on earth.

Zhang, Ye↗

NASA NTRS2016

Colonoscopy Screening in the US Astronaut Corps

BACKGROUND: Historically, colonoscopy screenings for astronauts have been conducted to ensure that astronauts are in good health for space missions. Recently this historical data has been identified as being useful for developing an occupational surveillance requirement. It can be used to assess overall colon health and to have a point of reference for future tests in current and former astronauts, as well as to follow-up and track rates of colorectal cancer and polyps. These rates can be compared to military and other terrestrial populations. In 2003, the active astronaut colonoscopy requirements changed to require less frequent colonoscopies. Since polyp removal during a colonoscopy is an intervention that prevents the polyp from potentially developing into cancer, the procedure decreases the individual's risk for colon cancer. The objective of this study is to evaluate the possible effect of increased follow-up times between colonoscopies on the number and severity of polyps identified during the procedures among both current and former NASA astronauts. Initial results and forward work regarding astronaut colonoscopy screenings will be presented. METHODS: A retrospective study of all colonoscopy procedures performed on NASA astronauts between 1962 and 2015 (both during active career and retirement) was conducted by review of the JSC Clinic Electronic Medical Record and Lifetime Surveillance of Astronaut Health (LSAH) database for colonoscopy screening procedures and pathology reports. The timeframe of interest was from the time of selection into the Astronaut Corps through May 2015 or death. For each colonoscopy report, the following data were captured: date of procedure, age at time of procedure, reason for procedure, quality of bowel prep, completion of procedure and/or reason for termination of procedure, findings of procedure, subsequent treatment (if any), recommended follow-up interval, actual follow up interval, family history of polyps or colon cancer, and other significant items or discrepancies. The population consisted of 338 astronauts: 52 females, 286 males. Of these, 56 were deceased, and 11 astronauts had no record of any colonoscopies. Because of a screening requirement change in 2003, analyses were conducted to determine if there were differences between the two time periods. One-sided Wilcoxon rank sum tests were used to identify statistically significant differences between the two time periods. RESULTS: There was a combined total of 1,964 colonoscopy screenings identified. The average follow-up intervals between colonoscopies were indeed longer after the screening requirement change than before the change. The mean follow-up interval pre -2003 was 3.59 years, while post-2003 it increased to 4.35 years. The statistical significance of this difference was confirmed using a one sided Wilcoxon rank sum test which yielded p<.001. Colonoscopies performed after the requirement change tended to have a higher incidence and greater severity of polyps. From pre-2003 to post-2003 the percentage of colonoscopy procedures yielding no polyps decreased from 83.77% to 74.70%. Not only did post-2003 procedures yield more polyp findings, but the polyps recorded were more often of severe pathology. Before 2003 3.62% of colonoscopy findings were polyps of the hyperplastic type (the least severe polyp type) and only 3.35% were of greater severity. Post-2003, 4.21% of findings were hyperplastic polyps while 11.44% were of greater severity. Upon the investigation of other possible contributing factors to these results, we also found that mean age post-2003 was 54.55 years which was significantly higher than during the pre-2003 timeframe (47.32 years). This was observed with a one-sided Wilcoxon rank sum test, resulting in a p<0.001. The increased average age of astronauts could also be a contributing factor to the greater number of polyps found since the risk of developing polyps increases with age. Further work is needed to better understand the increased incidence and greater severity of polyps found in astronaut colonoscopy outcomes.

Masterova, K.↗

NASA NTRS2015

Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of sequential proton and iron, radiation species relevant to spaceflight. When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerts pro-osteogenic effects apart from its previously demonstrated anti-resorptive action, which may be one of the mechanisms underlying its radioprotective effect on bone. In conclusion, a diet enriched in certain types of antioxidants may be useful as an intervention for radiation-induced bone loss.

Bone-loss↗

NASA NTRS2015

Dietary Supplement Attenuates Radiation-Induced Osteoclastogenic and Oxidative Stress-Related Responses and Protects Adult Mice from Radiation-Induced Bone Loss

Our central hypothesis is that oxidative stress plays a key role in cell dysfunction and progressive bone loss caused by radiation exposure during spaceflight. In animal studies, excess free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. We previously reported that exposure to low or high-LET radiation rapidly increases expression levels of pro-osteoclastogenic and oxidative stress-related genes in bone and marrow, followed by pathological changes in skeletal structure. To screen various antioxidants for radioprotective effects on bone, 4 month old, male C57Bl6/J mice were treated with a dietary antioxidant cocktail, injectable alpha-lipoic acid, or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs total body radiation and one day later marrow cells were collected and the relevant genes analyzed for expression levels. Of the candidates tested, DP was most effective in reducing bone resorption-related gene expression. Microcomputed tomography revealed that DP also prevented the radiation-induced deterioration of skeletal microarchitecture, as indicated by percent bone volume, trabecular spacing and trabecular number. DP had similar protective effects on skeletal structure after sequential exposure to protons (0.5 Gy, 150MeV/n) and 56Fe 0.5Gy, 600 MeV/n). When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerted pro-osteogenic effects apart from previously identified anti-resorptive actions, which may contribute to radioprotection of skeletal tissue. In conclusion, a diet enriched in certain types of antioxidants and polyphenols such as DP may be useful as an intervention to protect tissues from degenerative effects of ionizing radiation.

Globus, Ruth↗

NASA NTRS2016

Non-OH Chemistry in Oxidation Flow Reactors for the Study of Atmospheric Chemistry Systematically Examined by Modeling

Oxidation flow reactors (OFRs) using low-pressure Hg lamp emission at 185 and 254 nm produce OH radicals efficiently and are widely used in atmospheric chemistry and other fields. However, knowledge of detailed OFR chemistry is limited, allowing speculation in the literature about whether some non-OH reactants, including several not relevant for tropospheric chemistry, may play an important role in these OFRs. These non-OH reactants are UV radiation, O(1D), O(3P), and O3. In this study, we investigate the relative importance of other reactants to OH for the fate of reactant species in OFR under a wide range of conditions via box modeling. The relative importance of non-OH species is less sensitive to UV light intensity than to relative humidity (RH) and external OH reactivity (OHRext), as both non-OH reactants and OH scale roughly proportional to UV intensity. We show that for field studies in forested regions and also the urban area of Los Angeles, reactants of atmospheric interest are predominantly consumed by OH. We find that O(1D), O(3P), and O3 have relative contributions to VOC consumption that are similar or lower than in the troposphere. The impact of O atoms can be neglected under most conditions in both OFR and troposphere. Under pathological OFR conditions of low RH and/or high OHRext, the importance of non-OH reactants is enhanced because OH is suppressed. Some biogenics can have substantial destructions by O3, and photolysis at non-tropospheric wavelengths (185 and 254 nm) may also play a significant role in the degradation of some aromatics under pathological conditions. Working under low O2 with the OFR185 mode allows OH to completely dominate over O3 reactions even for the biogenic species most reactive with O3. Non-tropospheric VOC photolysis may have been a problem in some laboratory and source studies, but can be avoided or lessened in future studies by diluting source emissions and working at lower precursor concentrations in lab studies, and by humidification. SOA photolysis is shown to be insignificant for most functional groups, except for nitrates and especially aromatics, which may be photolyzed at high UV flux settings. Our work further establishes the OFR's usefulness as a tool to study atmospheric chemistry and enables better experiment design and interpretation, as well as improved future reactor design.

Peng, Zhe↗