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At least 37 records · Page 2

Shuttle-food consumption, body composition and body weight in women

An experiment is conducted to determine whether the NASA Space Shuttle food system can provide the food and fluid required to mitigate weight loss and physical decomposition in 12 female subjects for 28 days. Subjects receive only foods from the Space Shuttle system for four weeks within an 11-wk monitoring period. Dual-energy X-ray absorptiometry is employed throughout the trial period to study lean body mass, percent body fat, and energy-intake levels with attention given to differences the experimental diet and the subjects' typical diet. Percent body fat is found to change significantly with losses of less than 0.05 percent, whereas energy intake based on autonomous diet choices by the participants does not vary significantly. Lean body mass remains unchanged throughout the study in which the subjects receive a relatively low-fat and low-protein menu. The 100 items on the space shuttle list of approved food items are shown to provide a palatable dietary framework for maintaining the health of female astronauts.

Lane, Helen W.↗

Common endocrine control of body weight, reproduction, and bone mass

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

NASA Discipline Regulatory Physiology↗

Body composition changes in men and women after 2-3 weeks of bed rest

Several parameters of body composition were measured in eight men before and after 14 days of continuous recumbency, and in eight women before and after 17 days of recumbency. The parameters measured included body weight, body water, body potassium, plasma volume, and plasma protein concentrations. From these, values were derived for body fat content, lean body mass, body mass, and circulating plasma proteins. In general, the men and women responded similarly to continuous recumbency. Characteristically, there was significant reduction of plasma volume and body potassium in both groups. The women showed a significant reduction in circulating plasma protein, entirely in the albumin fraction; a similar change was observed in the men. The women, but not the men, showed a significant increase in circulating fibrinogen. Both men and women lost body cell mass, while body fat content remained the same or tended to increase slightly. It is expected that similar changes would occur in weightlessness. It is further concluded that women should tolerate the weightlessness of space flight physiologically as well as men.

Pace, N.↗

Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure

BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, P<0.05) with similar body weights. Myocyte width was also increased in 4-week and 7-week AS mice compared with controls (19.0+/-0.8 and 25.2+/-1.8 versus 14. 1+/-0.5 microm, respectively, P<0.01). By 7 weeks, AS myocytes displayed branching with distinct differences in intercalated disk size and staining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides. CONCLUSIONS: Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.

NASA Discipline Cardiopulmonary↗

Morphological traits for allometric scaling of the European Sea Bass Dicentrarchus labrax (Linnaeus, 1758) from Southern Portugal population

Abstract The present study aimed to determine the allometric scaling among a selection of morphological traits in European sea bass ( Dicentrarchus labrax ) to estimate fish body weight. A set of morphological traits (fish body weight, length, height, and width) were directly measured in 146 fish of a recirculating aquaculture system, with body weights ranging from 17.11 to 652.21 g. In addition, a collection of digital imagery of each anesthetized fish from the side and top views were used to estimate other traits (indirect measures). Multiple regression analysis and regression coefficients were calculated using all possible combinations of biometric data (predictors) to estimate fish body weight, applying different numerical fitting models (linear, log‐linear, quadratic, exponential). The results showed that the best combination of traits for estimating fish body weight were fish body width, length and height, collected from direct measure ( R 2 = 0.995), for a log‐linear model fitting, which revealed more accurate determinations than the most commonly used length–weight relationship. Nevertheless, other combinations of morphological traits and fitting models were also found to be suitable in successfully predict fish body weight, with variability ranging between 92.5% and 98.5%. For indirect measures, the best predictor was a combination of traits from top view (width, eye distance and area without fins) fitted with a log‐linear function. These results comprise a relevant baseline in supporting the high potential of noninvasive methods to accurately follow the growth of European sea bass juveniles, recurring to imagery analysis of anesthetized fish. It has major potential applications in feeding consumption trials and fish growth models, as it allows for continuously following up fish growth under different experimental conditions without therein distress derived from manipulation.

Azevedo, Ana↗

Nutritional Requirements for Space Station Freedom Crews

The purpose of this report was to set preliminary nutritional requirements for crewmembers flying from 90 to 180 day missions on Space Station Freedom. Specific recommendations included providing crewmembers with in flight feedback on nutritional intake, weight and strength, and incorporating issues of energy intake, body weight, body composition, strength, and protein intake in the flight medicine program. Exercise must be considered an integral part of any plan to maintain nutritional status, especially those modes that stress the skeleton and maintain body weight. Nutrient intake, amount of exercise, and drugs ingested must be recorded daily; high priority should be given to development of fully automated record systems that minimize astronauts' effort. A system of nutritional supplements should be developed to provide a method for reducing intake deficits that become apparent. Finally, post flight monitoring should include bone density, muscle mass and function, and iron status at three and six months after landing.

Lane, Helen W.↗

Load Variation Influences on Joint Work During Squat Exercise in Reduced Gravity

Resistance exercises that load the axial skeleton, such as the parallel squat, are incorporated as a critical component of a space exercise program designed to maximize the stimuli for bone remodeling and muscle loading. Astronauts on the International Space Station perform regular resistance exercise using the Advanced Resistive Exercise Device (ARED). Squat exercises on Earth entail moving a portion of the body weight plus the added bar load, whereas in microgravity the body weight is 0, so all load must be applied via the bar. Crewmembers exercising in microgravity currently add approx.70% of their body weight to the bar load as compensation for the absence of the body weight. This level of body weight replacement (BWR) was determined by crewmember feedback and personal experience without any quantitative data. The purpose of this evaluation was to utilize computational simulation to determine the appropriate level of BWR in microgravity necessary to replicate lower extremity joint work during squat exercise in normal gravity based on joint work. We hypothesized that joint work would be positively related to BWR load.

DeWitt, John K.↗

Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone area, and increased trabecular separation. Both GH and E reduced cancellous osteopenia, although employing different mechanisms. GH reduced the decrease in trabecular thickness, whereas E reduced the decrease in trabecular number and the increase in trabecular separation. Hypophysectomy reduced both Tb.MAR and Tb.BFR while treatment with GH enhanced them. This investigation has shown that Hx and GH have a dramatic impact on selected static and dynamic indices of rat cortical and cancellous histomorphometry. Furthermore, the mechanisms of action of GH and E differ, and suggest that some of the skeletal changes associated with Hx are caused by deficiencies in estrogen as well as deficiencies in growth hormone.

NASA Discipline Regulatory Physiology↗

Stress, Aging and Thirst

After growth during adolesence, total body water decreases progressively with aging from 65% of body weight to about 53% of body weight in the 70th decade; a majority of the loss occurs from the extracellular volume, from 42% to about 25%, respectively. Cellular volume also reaches equilibrium in the 70th decade at about 25% of body weight. Various stresses such as exercise, heat and attitude exposure, ad prior dehydration attenuate voluntary fluid intake (involuntary dehydration). Voluntary fluid intake appears to decrease with aging (involuntary dehydration in this sense aging can be considered as a stress. Kidney function and muscle mass (80% water) decrease somewhat with aging, and voluntary fluid intake (thirst) is also attenuated. Thirst is stimulated by increasing osmolality (hypernatremia) of the extracellular fluid and by decreased extracellular volume (mainly plasma volume) which act to increase intracellular fluid volume osmolality to activiate drinking. The latter decreases fluid compartment osmolality which ' It terminates drinking. However, this drinking mechanism seems to be attenuated with aging such that increasing plasma osmolality no longer stimulates fluid intake appropriately. Hypernatremia in the elderly has been associated all too frequently with greater incidence of bacterial infection and increased mortality. Involuntary dehydration can be overcome in young men by acclimation to an intermittent exercise-in-heat training program. Perhaps exercise training in the elderly would also increase voluntary fluid intake and increase muscle mass to enhance retention of water.

Greenleaf, John E.↗

Continuous exposure of animals to methylisobutylketone

Continuous exposure of dogs, monkeys, mice, and rats to MIBK for two weeks and all animals except mice for 90 days resulted in measurable adverse effects only in the case of rats. Rat kidney weights and kidney to body weight ratios were significantly elevated after exposure to 410 mg/cu m for two weeks, and kidney and liver organ weights and organ to body weight ratios were elevated after exposure to 820 mg/cu m for two weeks and to 410 mg/cu m for 90 days.

Vernot, E. H.↗

Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials

Our research supported the dose selection recommendations for adolescents in the US Food and Drug Administration (FDA) Guidance on Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. The FDA Guidance states that for drugs administered as a flat dose in adults and data showing no clinically meaningful effect of body size on drug exposure and toxicity in adults, a minimum body weight threshold may need to be defined to prevent adolescents who have a lower body weight from exceeding adult exposures. Our review of adult population pharmacokinetic analyses of new molecular entities approved for oncology between January 2015 and March 2021 suggested that 40 kg (the approximate median body weight of a 12-year-old) is generally the lower end of the body weight range that has no clinically relevant effect on drug pharmacokinetics or safety. In conclusion, the minimum body weight threshold and selection of an appropriate dose for adolescents in relevant adult oncology clinical trials should ultimately be determined based on available data on pharmacokinetics or pharmacodynamics of the investigational drug with consideration of body size effect on drug exposure, toxicity, and efficacy data (if available), the therapeutic index of the drug, and dose- and exposure-response relationships in adults.

60 APPLIED LIFE SCIENCES↗

Impact of the built, social, and food environment on long‐term weight loss within a behavioral weight loss intervention

Abstract Background Behavioral weight loss interventions can lead to an average weight loss of 5%–10% of initial body weight, however there is wide individual variability in treatment response. Although built, social, and community food environments can have potential direct and indirect influences on body weight (through their influence on physical activity and energy intake), these environmental factors are rarely considered as predictors of variation in weight loss. Objective Evaluate the association between built, social, and community food environments and changes in weight, moderate‐to‐vigorous physical activity (MVPA), and dietary intake among adults who completed an 18‐month behavioral weight loss intervention. Methods Participants included 93 adults (mean ± SD; 41.5 ± 8.3 years, 34.4 ± 4.2 kg/m 2 , 82% female, 75% white). Environmental variables included urbanicity, walkability, crime, Neighborhood Deprivation Index (includes 13 social economic status factors), and density of convenience stores, grocery stores, and limited‐service restaurants at the tract level. Linear regressions examined associations between environment and changes in body weight, waist circumference (WC), MVPA (SenseWear device), and dietary intake (3‐day diet records) from baseline to 18 months. Results Grocery store density was inversely associated with change in weight ( β = −0.95; p = 0.02; R 2 = 0.062) and WC ( β = −1.23; p < 0.01; R 2 = 0.109). Participants living in tracts with lower walkability demonstrated lower baseline MVPA and greater increases in MVPA versus participants with higher walkability (interaction p = 0.03). Participants living in tracts with the most deprivation demonstrated greater increases in average daily steps ( β = 2048.27; p = 0.02; R 2 = 0.039) versus participants with the least deprivation. Limited‐service restaurant density was associated with change in % protein intake ( β = 0.39; p = 0.046; R 2 = 0.051). Conclusion Environmental factors accounted for some of the variability (<11%) in response to a behavioral weight loss intervention. Grocery store density was positively associated with weight loss at 18 months. Additional studies and/or pooled analyses, encompassing greater environmental variation, are required to further evaluate whether environment contributes to weight loss variability.

Tewahade, Selam↗

Development of a Sensorimotor Ground Analog from Astronaut Postflight Experience

Exploration class missions including Artemis, Gateway, and beyond will require a new level of autonomy around periods of gravitational transition, where sensorimotor disturbances are great. Because of this, there is a need to define sensorimotor assessment thresholds that indicate when performance in operational tasks might be impacted or unsafe. To define these thresholds, a Sensorimotor Adaptation Analog (SAA) was proposed that could induce varying levels of sensorimotor disorientation through combined vestibular, visual, and proprioceptive disruptions. The purpose of this study was to gather subjective feedback on the SAA from previously flown astronauts that would mimic their post-flight experience and functional performance immediately after landing (R+0-4hrs; high level) and post-landing (R+24-48hrs; low level). The SAA consisted of galvanic vestibular stimulation (GVS), visual disorientation goggles, and a weighted suit to alter proprioceptive feedback and replicate subjective heaviness. A random sum-of-sines profile between 0-1Hz was used for the GVS with peak amplitudes ranging from 1-4mA. The GVS was applied first at the low (2mA) and high (3mA) levels, followed by the weighted suit alone, then combined with the GVS at the low (20% body weight) and high levels (40% body weight). Last, the disorientation goggles were applied alongside both the GVS and weighted suit at the low (0.07-0.10+ blood alcohol content (BAC)) and high (0.12-0.15+ BAC) levels. Each element of the SAA could be increased or decreased depending on crew feedback to find the disorientation levels that best matched their experience. Five USOS astronauts (1 male, 4 female) who had previously flown (average time since flight: 377 days) participated. Crewmembers reported that GVS alone replicated ~80-90% of their post-flight performance with the weighted suit fine-tuning the experience to replicate an additional 5-10% of their experience. Crewmembers did not believe the disorientation goggles represented either the visual disruptions or illusory sensations that they experienced, nor did they impact performance in post-flight tasks similarly. The final SAA, resulting from crewmember feedback, includes the GVS at the levels described above and the weighted suit at 15% and 30% body weight. The disorientation goggles were removed from SAA. These results provided a more realistic SAA that can be used to define the sensorimotor assessment thresholds through ground subjects and potentially expanded for use in countermeasure testing and as a pre-flight training tool.

S. C. Moudy↗

Current Status of Radiopharmaceutical Therapy

In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while minimizing radiation exposure to untargeted cells. Examples of current RPTs include thyroid ablation with the administration of {sup 131}I, treatment of liver cancer with {sup 90}Y microspheres, the treatment of bony metastases with {sup 223}Ra, and the treatment of neuroendocrine tumors with {sup 177}Lu-DOTATATE. New RPTs are being developed where radionuclides are incorporated into systemic targeted therapies. To assure that RPT is appropriately implemented, advances in targeting need to be matched with advances in quantitative imaging and dosimetry methods. Currently, radiopharmaceutical therapy is administered by intravenous or locoregional injection, and the treatment planning has typically been implemented like chemotherapy, where the activity administered is either fixed or based on a patient’s body weight or body surface area. RPT pharmacokinetics are measurable by quantitative imaging and are known to vary across patients, both in tumors and normal tissues. Therefore, fixed or weight-based activity prescriptions are not currently optimized to deliver a cytotoxic dose to targets while remaining within the tolerance dose of organs at risk. Methods that provide dose estimates to individual patients rather than to reference geometries are needed to assess and adjust the injected RPT dose. Accurate doses to targets and organs at risk will benefit the individual patients and decrease uncertainties in clinical trials. Imaging can be used to measure activity distribution in vivo, and this information can be used to determine patient-specific treatment plans where the dose to the targets and organs at risk can be calculated. The development and adoption of imaging-based dosimetry methods is particularly beneficial in early clinical trials. In this work we discuss dosimetric accuracy needs in modern radiation oncology, uncertainties in the dosimetry in RPT, and best approaches for imaging and dosimetry of internal radionuclide therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗