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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

Physiologic Responses Produced by Active and Passive Personal Cooling Vests

Personal thermoregulatory systems which provide chest cooling are used in the industrial and aerospace environments to alleviate thermal stress. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objectives of this study were to document and compare the subjects' response to three cooling vests in their recommended configurations. The Life Enhancement Tech (LET) lightweight active cooling vest with cap, the MicroClimate Systems Change of Phase garment (MCS), and the Steele Vest were each used to cool the chest regions of 12 male and 8 female Healthy subjects (21 to 69 yr.) in this study. The subjects, seated in an upright position at normal room temperature (approx. 22 C), were tested for 60 min. with one of the cooling garments. The LET active garment had an initial coolant fluid inlet temperature of 60 F, and was ramped down to 50 F. Oral, right and left ear canal temperatures were logged manually every 5 min. Arm, leg, chest and rectal temperatures; heart rate; and respiration were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. For men, all three vests had similar, significant cooling effects. Decreases in the average rectal temperature, oral temperature, and ear canal temperatures were approximately 0.2 C, 0.2 C and 0.1 C, respectively. In contrast to the men, the female subjects wearing the MCS and Steel vests had similar cooling responses in which the core temperature remained elevated and oral and ear canal temperatures did not drop. The LET active garment cooled most of the female subjects in this study; rectal, oral and ear temperature decreased about 0.2 C, 0.3 C and 0.3 C, respectively. These results show that the garment configurations tested do not elicit a similar thermal response in all subjects. A gender difference is evident. The LET active garment configuration was most effective in decreasing temperatures of the female subjects; the MCS vest was least effective. For male subjects, the three vests appear to be more nearly equivalent. The active garment system under study included a cooling cap, which may account for some of the difference in response.

Ku, Yu-Tsuan E.↗
NASA NTRS2003

Effect of High Impact or Non-impact Loading Activity on Bone Bending Stiffness and Mineral Density

Material properties of conical bone, including mineral density (BMD) and its geometry is closely related to its load-carrying capacity. These two primary components determine the strength of conical bone. High impact loading involving acceleration and deceleration movements used in gymnastics induce higher BMD of the affected bone compared to the non-impact acceleration and deceleration movements used in swimming. Study of these two groups of athletes on bone bending stiffness has not been reported. The purpose of this study was to compare differences in bone bending stiffness and BMD between competitive female synchronized swimmers and female gymnasts. Thirteen world class female synchronized swimmers (SYN) and 8 female gymnasts (GYM), mean age 21 +/- 2.9 yr. were recruited for this study. We used a mechanical response tissue analyzer (Gaitscan, NJ) to calculate EI, where E is Young's modulus of elasticity and I is the cross-sectional moment of inertia. EI was obtained from tissue response to a vibration probe placed directly on the skin of the mid-region of tibia and ulna. BMD of the heel and wrist were measured with a probe densitometer (PIXI, Lunor, WI). The SYN were taller than (p < 0.05) the GYM but weighed the same as the GYM. EI obtained from tibia and ulna of the SYN (291 +/- 159 and 41 +/- 19.4, respectively) were not significantly different from thc GYM (285 +/- 140 and 44 +/- 18.3, respectively). BMD of the heel and wrist in GYM were higher than in SYN (p < 0.001). High impact weight-bearing activities promote similar bone strength but greater BMD response than non-impact activities performed in a buoyant environment.

Liang, Michael T. C.↗
NASA NTRS2008

Determining Exercise Strength Requirements for Astronaut Critical Mission Tasks: Reaching Under G-Load

The critical mission tasks assessments effort seeks to determine the physical performance requirements that astronauts must meet in order to safely and successfully accomplish lunar exploration missions. These assessments will determine astronaut preflight strength, fitness, and flexibility requirements, and the extent to which exercise and other countermeasures must prevent the physical deconditioning associated with prolonged weightlessness. The purpose is to determine the flexibility and strength that crewmembers must possess in order to reach Crew Exploration Vehicle controls during maneuvers that result in sustained acceleration levels ranging from 3.7G to 7.8G. An industry standard multibody dynamics application was used to create human models representing a 5th percentile female, a 50th percentile male, and a 95th percentile male. The additional mass of a space suit sleeve was added to the reaching arm to account for the influence of the suit mass on the reaching effort. The human model was merged with computer models of a pilot seat and control panel for the Crew Exploration Vehicle. Three dimensional paths were created that guided the human models hand from a starting position alongside its thigh to three control targets: a joystick, a keyboard, and an overhead switch panel. The reaching motion to each target was repeated under four vehicle acceleration conditions: nominal ascent (3.7G), two ascent aborts (5.5G and 7.8G) and lunar reentry (4.6G). Elbow and shoulder joint angular excursions were analyzed to assess range of motion requirements. Mean and peak elbow and shoulder joint torques were determined and converted to equivalent resistive exercise loads to assess strength requirements. Angular excursions for the 50th and 95th percentile male models remained within joint range of motion limits. For the 5th percentile female, both the elbow and the shoulder exceeded range of motion limits during the overhead reach. Elbow joint torques ranged from 10 N-m (nominal ascent) to 60 N-m (ascent abort). Shoulder joint torques ranged from 65 N-m (nominal ascent) to 280 N-m (ascent abort). Maximal equivalent exercise loads reached 30 lb in tricep extension, 9 lb in bicep curl, 110 lb in unilateral pullover and unilateral bench press for nominal conditions (lunar reentry), and 188 lb in unilateral pullover and unilateral bench press. The location of the pilot seat was found to be inadequately located to allow a 5th percentile female to reach the switches on the overhead panel. Elbow strength requirements were found to be well within population norms. Shoulder strength was found to be a limiting factor. Reaching under nominal ascent and lunar reentry conditions was found to require near maximal shoulder strength. Reaching under ascent abort conditions requires shoulder strength well beyond population norms. Pilot seats must adjust to accomodate a 5th percentile female. Exercise countermeasures must maintain maximal pullover and bench press strength to allow pilots to reach and operate controls during lunar reentry. Reaching will not be possible during ascent abort conditions. Flight controls should be built into armrests or flight control must be accomplished by autonomous systems during acceleration exceeding 4.6G.

Schaffner, Grant↗
NASA NTRS2013

Impact of Gender on Pharmocokinetics of Intranasal Scopolamine

Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS), which is commonly experienced by astronauts during space missions. The bioavailability and pharmacokinetics (PK) were evaluated under IND guidelines. Since information is lacking on the effect of gender on the PK of Scopolamine, we examined gender differences in PK parameters of INSCOP at three dose levels of 0.1, 0.2 and 0.4 mg. Methods: Plasma scopolamine concentrations as a function of time data were collected from twelve normal healthy human subjects (6 male/6 female) who participated in a fully randomized double blind crossover study. The PK parameters were derived using WinNonlin. Covariate analysis of PK profiles was performed using NONMEN and statistically compared using a likelihood ratio test on the difference of objective function value (OFV). Statistical significance for covariate analysis was set at P<0.05(ΔOFV=3.84). Results: No significant difference in PK parameters between male and female subjects was observed with 0.1 and 0.2 mg doses. However, CL and Vd were significantly different between male and female subjects at the 0.4 mg dose. Results from population covariate modeling analysis indicate that a onecompartment PK model with first-order elimination rate offers best fit for describing INSCOP concentration-time profiles. The inclusion of sex as a covariate enhanced the model fitting (ΔOFV=-4.1) owing to the genderdependent CL and Vd differences after the 0.4 mg dose. Conclusion: Statistical modeling of scopolamine concentration-time data suggests gender-dependent pharmacokinetics of scopolamine at the high dose level of 0.4 mg. Clearance of the parent compound was significantly faster and the volume of distribution was significantly higher in males than in females, As a result, including gender as a covariate to the pharmacokinetic model of scopolamine offers the best fit for PK modeling of the drug at dose of 0.4 mg or higher.

Putcha, L.↗
NASA NTRS2015

Astronaut Preflight Cardiovascular Variables Associated with Vascular Compliance are Highly Correlated with Post-Flight Eye Outcome Measures in the Visual Impairment Intracranial Pressure (VIIP) Syndrome Following Long Duration Spaceflight

The detection of the first VIIP case occurred in 2005, and adequate eye outcome measures were available for 31 (67.4%) of the 46 long duration US crewmembers who had flown on the ISS since its first crewed mission in 2000. Therefore, this analysis is limited to a subgroup (22 males and 9 females). A "cardiovascular profile" for each astronaut was compiled by examining twelve individual parameters; eleven of these were preflight variables: systolic blood pressure, pulse pressure, body mass index, percentage body fat, LDL, HDL, triglycerides, use of anti‐lipid medication, fasting serum glucose, and maximal oxygen uptake in ml/kg. Each of these variables was averaged across three preflight annual physical exams. Astronaut age prior to the long duration mission, and inflight salt intake was also included in the analysis. The group of cardiovascular variables for each crew member was compared with seven VIIP eye outcome variables collected during the immediate post‐flight period: anterior-posterior axial length of the globe measured by ultrasound and optical biometry; optic nerve sheath diameter, optic nerve diameter, and optic nerve to sheath ratio‐ each measured by ultrasound and magnetic resonance imaging (MRI), intraocular pressure (IOP), change in manifest refraction, mean retinal nerve fiber layer (RNFL) on optical coherence tomography (OCT), and RNFL of the inferior and superior retinal quadrants. Since most of the VIIP eye outcome measures were added sequentially beginning in 2005, as knowledge of the syndrome improved, data were unavailable for 22.0% of the outcome measurements. To address the missing data, we employed multivariate multiple imputation techniques with predictive mean matching methods to accumulate 200 separate imputed datasets for analysis. We were able to impute data for the 22.0% of missing VIIP eye outcomes. We then applied Rubin's rules for collapsing the statistical results across our 200 multiply imputed data sets to assess the canonical correlation between the eye outcomes and the twelve astronaut cardiovascular variables available for all 31 subjects. Results: A highly significant canonical correlation was observed among the canonical solutions (p<.00001), with an average best canonical correlation of.97. The results suggest a strong association between astronauts' measures of cardiovascular health and the seven eye outcomes of the VIIP syndrome used in this analysis. Furthermore, the "joint test" revealed a significant difference in cardiovascular profile between male and female astronauts (Prob > F = 0.00001). Overall, female astronauts demonstrated a significantly healthier cardiovascular status. Individually, the female astronauts had significantly healthier profiles on seven of twelve cardiovascular variables than the men (p values ranging from <0.0001 to <0.05). Male astronauts did not demonstrate significantly healthier values on any of the twelve cardiovascular variables measured

Otto, Christian↗
NASA NTRS2016

NASA Astronaut Urinary Conditions Associated with Spaceflight

INTRODUCTION: Spaceflight is associated with many factors which may promote kidney stone formation, urinary retention, and/or Urinary Tract Infection (UTI). According to ISS mission predictions supplied by NASA's Integrated Medical Model, kidney stone is the second and sepsis (urosepsis as primary driver) the third most likely reason for emergent medical evacuation from the International Space Station (ISS). METHODS: Inflight and postflight medical records of NASA astronauts were reviewed for urinary retention, UTI and kidney stones during Mercury, Gemini, Apollo, Mir, Shuttle, and ISS expeditions 1-38. RESULTS: NASA astronauts have had 7 cases of kidney stones in the 12 months after flight. Three of these cases occurred within 90 to 180 days after landing and one of the seven cases occurred in the first 90 days after flight. There have been a total of 16 cases (0.018 events per person-flights) of urinary retention during flight. The event rates per mission are nearly identical between Shuttle and ISS flights (0.019 vs 0.021 events per person-flights). In 12 of the 16 cases, astronauts had taken at least one space motion sickness medication. Upon further analysis, it was determined that the odds of developing urinary retention in spaceflight is 3 times higher among astronauts who took promethazine. The female to male odds ratio for inflight urinary retention is 11:14. An astronaut with urinary retention is 25 times more likely to have a UTI with a 17% infection rate per mission. There have been 9 reported UTIs during spaceflight. DISCUSSION: It is unclear if spaceflight carries an increased post-flight risk of kidney stones. Regarding urinary retention, the female to male odds ratio is higher during flight compared to the general population where older males comprise almost all cases due to prostatic hypertrophy. This female prevalence in spaceflight is even more concerning given the fact that there have been many more males in space than females. Terrestrial medications with a known side effect of urinary retention are also associated with urinary retention during flight. However, not all cases of urinary retention surrounded medication use inflight. It is also known that UTI is a terrestrial cause of urinary retention. Furthermore, the treatment of urinary retention with a urinary catheter may be more likely to initiate a UTI in space than on the ground, as aseptic techniques can be particularly challenging with an inexperienced provider in a free-floating environment. Inflight urinary retention and UTI have proven to be highly associated and urinary risks should be considered collectively when planning for space flight.

Law, Jennifer↗
NASA NTRS2019

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗
NASA NTRSDate not supplied

Evaluation of Aerobic Standards for Lunar Surface Extravehicular Activities

Introduction: As NASA prepares to return to the Moon, astronauts will need to be physically primed to successfully execute Extravehicular Activities (EVA) on the Lunar surface. Compared to past Apollo missions, Artemis missions will include EVAs of increased physical demand, frequency, intensity, and duration, thus requiring adequate fitness to successfully and safely complete mission objectives. The physical demand associated with partial gravity (g) EVAs on the Moon is expected to be greater compared to microgravity EVAs based on initial workload estimation. Currently, aerobic fitness standards for partial g EVAs are not well supported by high-fidelity data and require further research for establishing standards to protect crew health and performance during Lunar surface missions. Therefore, the aim of this investigation is to characterize metabolic data from Lunar analog simulations and in-flight crew population aerobic capacity data to validate the current NASA 3001 standard for celestial partial g aerobic fitness (aerobic capacity (VO_2pk) ≥36.5ml/kg/min). Methods: In order to evaluate aerobic fitness requirements for Lunar EVAs, the following were performed: 1) preliminary analysis of long-duration (6 hr) EVA analog simulations in the Neutral Buoyancy Laboratory (NBL) and the Active Response Gravity Offload System (ARGOS) to evaluate expected metabolic rates for 1/6 g EVAs (NBL: n=1 female; ARGOS: n=1 male) and 2) assessment of the current NASA 3001 celestial surface EVA aerobic standard (aerobic capacity (VO_2pk) ≥36.5ml/kg/min) with data from an ISS astronaut population (n=30 male + 13 female) captured before and during space flight (flight day 15). Preliminary Results: Average fractional aerobic capacity during simulated EVAs were 33%±7% VO_2pk and 23.3±7% VO_2pk in the NBL and ARGOS, respectively. This was within a previously predicted 30–40% sustainable work rate. Average metabolic rates for some tasks performed in the NBL, such as traverse (40.4% VO_2pk) and ingress (47.1% VO_2pk) were higher than the predicted sustainable work range. In ARGOS, the tasks with the greatest metabolic rates were object relocation (34.2% VO_2pk) and incapacitated crew rescue (27.0% VO_2pk). Characterization of ISS crewmember aerobic capacity determined that the average preflight VO_2pk was 42.1±5.4 ml/kg/min for females and 37.5±5.4 ml/kg/min for males. At preflight, 21.5% of crewmembers were below the 36.5 ml/kg/min in-mission aerobic standard for celestial surface EVA as outlined in NASA-STD-3001. In-flight, both female and male crewmembers experienced reductions in VO_2pk (11.7% and 10.9%, respectively), such that, during the mission, 62% of crewmembers were below the standard aerobic capacity level for celestial surface EVAs. Conclusions: Our preliminary data suggest that while average metabolic rates for simulated Lunar EVA fall within the 30–40% sustainable work range, task specific metabolic rates exceed this range and may indicate that greater fitness is necessary for more strenuous tasks expected to be performed on the Lunar surface. Additionally, deconditioning due to space flight results in most crewmembers falling below the current celestial partial g EVA standard, which may increase risk to crew health and performance and completing mission objectives for surface missions. Further research is necessary in Artemis-specific analog environments to validate the current NASA-3001 aerobic standard for celestial EVAs. Additionally, work is ongoing to validate the current NASA-3001 strength standard for celestial EVAs.

N.C. Strock↗
NASA NTRS1994

Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats

Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced. Microscopic lesions included degeneration of the seminiferous tubular cells, pyknosis or absence of germ cells, and hypospermia in the epididymis. Rats of the 600 ppm group had a slight decrease in thymic weight and a transient decrease in body weight. Results of the acute, 2-wk, and 13-wk inhalation studies indicate DMES concentrations of 1000 ppm and higher produce narcosis that rapidly disappears following exposure. Repeated exposure of rats to DMES at either 3000 ppm for 2 wk or 2000 ppm for 13 wk caused testicular atrophy and hypospermia in male rats. Female rats exposed to 2000 ppm for 13 wk had delayed estrous cycles. Toxicological effects in rats of the 600 ppm group were minimal and equivocal. The 160 ppm concentration was a no-observable-effect level (NOEL) for 13 wk of exposure to DMES.

NASA Discipline Number 04-10↗
NASA NTRS2000

Inducing jet-lag in older people: directional asymmetry

Twenty healthy elderly subjects (12 female, 8 male; mean age 81 years, range 67-87 years) each experienced a 15-day time isolation protocol in which they lived individually in a special laboratory apartment in which sleep and circadian rhythm measures could be taken. There were two experiments: one (6 females, 4 males) involved a 6-h phase advance of the sleep/wake cycle, and the other (6 females, 4 males) a 6-h phase delay. Each started with 5 baseline days, immediately followed by the phase shift. The subject was then held to the phase shifted routine for the remainder of the study. Rectal temperatures were recorded minute-by-minute throughout the entire experiment and each night of sleep was recorded using polysomnography. A directional asymmetry in phase-shift effects was apparent, with significantly more sleep disruption and circadian rhythm amplitude disruption after the phase advance than after the phase delay. Sleep disruption was reflected in reduced time spent asleep, and in changed REM latency, which increased in the phase advance direction but decreased in the phase delay direction. Although the phase advance led to a significant increase in wakefulness in the first half of the night, the phase delay did not lead to an equivalent increase in wakefulness during the second half of the night. Examination of both raw and 'demasked' circadian rectal temperature rhythms confirmed that phase adjustment was slow in both directions, but was less slow (and more monotonic) after the phase delay than after the phase advance. Subjective alertness suffered more disruption after the phase advance than after the phase delay.

NASA Discipline Regulatory Physiology↗
NASA NTRS1999

Sexually dimorphic development and binding characteristics of NMDA receptors in the brain of the platyfish

This study investigated age- and gender-specific variations in properties of the glutamate N-methyl-d-aspartate receptor (NMDAR) in a freshwater teleost, the platyfish (Xiphophorus maculatus). Prior localization of the immunoreactive (ir)-R1 subunit of the NMDAR protein (R1) in cells of the nucleus olfactoretinalis (NOR), a primary gonadotropin-releasing hormone (GnRH)-containing brain nucleus in the platyfish, suggests that NMDAR, as in mammals, is involved in modulation of the platyfish brain-pituitary-gonad (BPG) axis. The current study shows that the number of cells in the NOR displaying ir-R1 is significantly increased in pubescent and mature female platyfish when compared to immature and senescent animals. In males, there is no significant change in ir-R1 expression in the NOR at any time in their lifespan. The affinity of the noncompetitive antagonist ((3)H)MK-801 for the NMDAR is significantly increased in pubescent females while maximum binding of ((3)H)MK-801 to the receptor reaches a significant maximum in mature females. In males, both MK-801 affinity and maximum binding remain unchanged throughout development. This is the first report of gender differences in the association of NMDA receptors with neuroendocrine brain areas during development. It is also the first report to suggest NMDA receptor involvement in the development of the BPG axis in a nonmammalian vertebrate. Copyright 1999 Academic Press.

Non-NASA Center↗
NASA NTRS1995

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.

NASA Program Space Physiology and Countermeasures↗
NASA NTRS2005

Skeletal phenotype of growing transgenic mice that express a function-perturbing form of beta1 integrin in osteoblasts

Skeletal modeling entails the deposition of large amounts of extracellular matrix (ECM) to form structures tailored to withstand increasing mechanical loads during rapid growth. Specific ECM molecules bind to integrin receptors on the cell surface, thereby triggering a cascade of signaling events that affect critical cell functions. To evaluate the role of integrins during skeletal growth, transgenic mice were engineered to express a function-perturbing fragment of beta1 integrin consisting of the transmembrane domain and cytoplasmic tail under the control of the osteocalcin promoter (TG mice). Thus, transgene expression was targeted to mature cells of the osteoblast lineage, and herein we show that cultured cells resembling osteocytes from 90-day-old TG mice display impaired adhesion to collagen I, a ligand for beta1 integrin. To determine the influence of beta1 integrin on bones that are responsible for providing structural support during periods of rapid growth, we examined the phenotype of the appendicular skeleton in TG mice compared to wild type (WT) mice. According to radiographs, bones from mice of both genotypes between 14 and 90 days of age appeared similar in gross structure and density, although proximal tibiae from 35-90 days old TG mice were less curved than those of WT mice (72-92% TG/WT). Although there were only mild and transient differences in absolute bone mass and strength, once normalized to body mass, the tibial dry mass (79.1% TG/WT females), ash mass (78.5% TG/WT females), and femoral strength in torsion (71.6% TG/WT females) were reduced in TG mice compared to WT mice at 90 days of age. Similar effects of genotype on bone mass and curvature were observed in 1-year-old retired breeders, indicating that these phenotypic differences between TG and WT mice were stable well into adulthood. Effects of genotype on histomorphometric indices of cancellous bone turnover were minimal and evident only transiently during growth, but when present they demonstrated differences in osteoblast rather than osteoclast parameters. Together, these results suggest that integrin signals generated during growth enhance the acquisition of a skeletal mass, structure, and strength to withstand the mechanical loads generated by weight-bearing.

Antigens, CD29/genetics/metabolism↗
DOE OSTI2024

Brain‐age prediction: Systematic evaluation of site effects, and sample age range and size

Abstract Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain‐age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain‐age has highlighted the need for robust and publicly available brain‐age models pre‐trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain‐age model. Here we expand this work to develop, empirically validate, and disseminate a pre‐trained brain‐age model to cover most of the human lifespan. To achieve this, we selected the best‐performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain‐age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5–90 years; 53.59% female). The pre‐trained models were tested for cross‐dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8–80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9–25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age‐bins (5–40 and 40–90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain‐age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain ( https://centilebrain.org/#/brainAGE2 ), an open‐science, web‐based platform for individualized neuroimaging metrics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Development of a military-specific mesh-type computational phantom library and its application to internal dosimetry and in-field radiological triage screening

Estimates of organ-absorbed and committed doses to individuals exposed to radioactive materials via acute inhalation often rely on internal dose coefficients and detector responses from reference human computational models. To achieve more accurate dose assessments to United States Armed Forces service members exposed in-field, computational models with varying morphometric parameters representative of this population are necessary. The International Commission on Radiological Protection (ICRP) Publication 145 provides detailed mesh reference computational phantoms (MRCPs) for adult males and females, with morphometric parameters matched to the 50th percentile. Previously, these phantoms were 2D and 3D scaled to match desired height, mass, and secondary anthropomorphic parameters in the creation of the University of Florida / Memorial Sloan Kettering (UF/MSK) computational phantom library. To achieve body fat percentage targets required for accession into the US Armed Forces, muscle and fat volumes were adjusted accordingly, thus, creating the UF/Department of Defence computational phantom library presented in this study. A comprehensive library of mesh-type computational human phantoms was created, including 57 adult males and 49 adult females with morphometric parameters aligned with United States Armed Forces service members. Phantoms were restricted to a body mass index between 19 and 27.5, with body fat percentages below 26% for males and 36% for females. Specific absorbed fractions were computed for selected source and target combinations, demonstrating how variations in height and body mass influence energy absorption in target regions relative to the ICRP MRCPs. Radiation detector responses were also computed, revealing that higher body masses resulted in decreased registered counts in the detection volume. These findings highlight the importance of incorporating morphometric variability in computational phantoms to achieve more accurate dose assessments and radiation detection responses for United States Armed Forces service members who inhale radioactive materials in-field.

computational phantoms↗
DOE OSTI2025

Age at release affects developmental physiology and sex-specific phenotypic diversity of hatchery steelhead trout (Oncorhynchus mykiss)

Most steelhead trout hatcheries increase growth rate during rearing to produce and release yearling smolts for harvest augmentation, but natural steelhead exhibit variable age of smoltification, so this common rearing practice may not be ideal for programs focused on recovering imperiled wild stocks; therefore, it is important to investigate and compare alternative hatchery rearing methods that promote life history diversity. Over six consecutive years, the Winthrop National Fish Hatchery on the Methow River, WA reared and released paired groups of age-1 (S1) and age-2 (S2) steelhead smolts. To understand how the two rearing methods affected developmental ontogeny and life-history, fish were sampled prior to hatchery release for factors associated with smoltification (size, gill Na+/K+ ATPase activity, and a qualitative smolt phenotype) and sexual maturation (sex, pituitary and testis mRNA transcripts, gonadosomatic index, and plasma 11-ketotestosterone). Our objectives were to quantify levels of smoltification and male maturation during hatchery rearing, combine metrics to estimate residualism (failure to migrate upon release), and compare the treatments by sex. Overall, S2 rearing produced 7.8% more smolts and 44-fold (4.4 vs. 0.1%) more precociously mature males than S1 rearing. Conversely, S1 rearing produced 31.6% more residuals than S2 rearing. While the proportion of total male residuals was comparable between treatments, the S1 treatment produced approximately five-fold more female residuals (20.6 vs. 4.2%). Because residuals contribute minimally to adult returns and the number of returning adult females is critical to the success of salmonid supplementation efforts, developing rearing techniques that maximize migration in females is a management priority. Physiological assessments are useful for characterizing and quantifying the effects and risks of different hatchery rearing regimes on steelhead life-history, in addition to providing sex-specific guidance to inform and optimize conservation management goals in supplementation programs.

Middleton, Mollie A. (ORCID:0009000905577865)↗
DOE OSTI2026

Comparison of gene expression in the skin tissue of gray, humpback, and fin whales

Analyses of gene expression in the skin of several species of whales identified genes that are differentially expressed in association with environmental factors, suggesting that skin transcriptomics may provide a valuable tool for assessing physiological responses in marine mammals. Previous work exploring differing levels of gene expression has focused on odontocetes with comparatively limited investigation of skin gene expression has been explored in mysticetes. Here, we describe the identity of genes expressed in skin tissue of three species of baleen whales to establish a baseline of gene expression and compare gene identity and expression patterns across species. We also evaluate sex-specific differences in skin gene expression through a comparison of expression levels between males and females in gray and humpback whales. A total of 16 skin tissue samples were collected from free-ranging gray, humpback and fin whales off the central Oregon coast in the eastern North Pacific. Comparison of the expressed genes in the humpback and gray whale skin tissue to the blue whale reference database identified enriched gene ontology terms in the skin tissue of each species, suggesting genes over-represented in the whale skin related to cell epithelial development, regulation of gene expression and cell maintenance . Comparison of gene expression between male and female samples revealed sex-specific differences in gray and humpback whales. A differential gene expression analysis identified several x-linked genes that have been previously identified and show gene expression differences in male and female cetaceans, such as ZFX, DDX3X and USP9X. Establishing baseline skin gene expression profiles for these three baleen whale species sampled off the Oregon coast provides a foundation for linking transcriptome variation with physiological condition and environment.

Sremba, Angela↗
DOE OSTI2024

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011–30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

60 APPLIED LIFE SCIENCES↗