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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 739 records · Page 41
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics differed with acute and repeated administration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum testosterone level in ND-treated rats. • Taurine prevents ND-induced testicular toxicity and DNA damage. • Taurine shows antioxidant, anti-inflammatory, and anti-apoptotic effects.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating D-Galactosamine induced fulminant hepatic failure in Wistar rats

Genistein is an isoflavanoid abundantly found in soy. It has been found to play an important role in the prevention of various chronic diseases including cancer. In this study, we evaluated potential therapeutic properties of Genistein against D-Galactosamine (D-GalN) induced inflammation and hepatotoxicity in male Wistar rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal injection of D-GalN (700 mg/kgBW). Genistein (5 mg/kgBW/day) was given as pre-treatment for 30 days via intra-gastric route followed by D-GalN (700 mg/kgBW) injection. The hepatoprotective and curative effects of Genistein were evident from a significant decrease in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as prevention of histological damage by pre-treatment of Genistein. Genistein pre-treatment significantly inhibited the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly suppressed the production of D-GalN-induced proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. These inhibitory effects were associated with the suppression of nuclear factor-kappa B (NF-ĸB) activation, IKKα/β and Mitogen activated protein kinase (MAPK) phosphorylation by Genistein in D-GalN-treated animals. In conclusion, our results suggest that Genistein may serve as a potential supplement in the prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to maintain the redox potential and strengthens the antioxidant defense system of a cell. - Highlights: • First study to evaluate hepatoprotective effect of Genistein against D-GalN • Genistein prevents oxidative damage induced by D-GalN. • Genistein blunts iNOS, COX-2, NF-ĸB, IKKα/β and MAPK expression. • Genistein prevents D-GalN induced apoptosis and necrosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity

Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. - Highlights: • miRNAs were altered in Sertoli cells exposed to MC-LR. • Alerted genes were involved in different cell functions including the cell morphology. • MC-LR adversely affected Sertoli cell junction formation through the regulating miRNAs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Staphylococcal enterotoxin A regulates bone marrow granulocyte trafficking during pulmonary inflammatory disease in mice

Pulmonary neutrophil infiltration produced by Staphylococcal enterotoxin A (SEA) airway exposure is accompanied by marked granulocyte accumulation in bone marrow (BM). Therefore, the aim of this study was to investigate the mechanisms of BM cell accumulation, and trafficking to circulating blood and lung tissue after SEA airway exposure. Male BALB/C mice were intranasally exposed to SEA (1 μg), and at 4, 12 and 24 h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. Adhesion of BM granulocytes and flow cytometry for MAC-1, LFA1-α and VLA-4 and cytokine and/or chemokine levels were assayed after SEA-airway exposure. Prior exposure to SEA promoted a marked PMN influx to BAL and lung tissue, which was accompanied by increased counts of immature and/or mature neutrophils and eosinophils in BM, along with blood neutrophilia. Airway exposure to SEA enhanced BM neutrophil MAC-1 expression, and adhesion to VCAM-1 and/or ICAM-1-coated plates. Elevated levels of GM-CSF, G-CSF, INF-γ, TNF-α, KC/CXCL-1 and SDF-1α were detected in BM after SEA exposure. SEA exposure increased production of eosinopoietic cytokines (eotaxin and IL-5) and BM eosinophil VLA-4 expression, but it failed to affect eosinophil adhesion to VCAM-1 and ICAM-1. In conclusion, BM neutrophil accumulation after SEA exposure takes place by integrated action of cytokines and/or chemokines, enhancing the adhesive responses of BM neutrophils and its trafficking to lung tissues, leading to acute lung injury. BM eosinophil accumulation in SEA-induced acute lung injury may occur via increased eosinopoietic cytokines and VLA-4 expression. - Highlights: • Airway exposure to SEA causes acute lung inflammation. • SEA induces accumulation of bone marrow (BM) in immature and mature neutrophils. • SEA increases BM granulocyte or BM PMN adhesion to ICAM-1 and VCAM-1, and MAC-1 expression. • SEA induces BM elevations of CXCL-1, INF-γ, TNF-α, GM-CSF, G-CSF and SDF-1α. • Our results contribute to elucidating BM events during SEA-induced lung inflammation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach

Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastric juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses. - Highlights: • We outline a new in vivo model for hexavalent chromium reduction in the stomach. • We examine in vivo reduction for mice, rats, and humans under varying conditions. • Species differences in toxicokinetics may explain susceptibility. • We show that a simplified stomach reduction model is adequate for extrapolation. • Internal dose uncertainties still exist.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Discovery of a Series of Imidazo[4,5-b]pyridines with Dual Activity at Angiotensin II Type 1 Receptor and Peroxisome Proliferator-Activated Receptor-[gamma]

Mining of an in-house collection of angiotensin II type 1 receptor antagonists to identify compounds with activity at the peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) revealed a new series of imidazo[4,5-b]pyridines 2 possessing activity at these two receptors. Early availability of the crystal structure of the lead compound 2a bound to the ligand binding domain of human PPAR{gamma} confirmed the mode of interaction of this scaffold to the nuclear receptor and assisted in the optimization of PPAR{gamma} activity. Among the new compounds, (S)-3-(5-(2-(1H-tetrazol-5-yl)phenyl)-2,3-dihydro-1H-inden-1-yl)-2-ethyl-5-isobutyl-7-methyl-3H-imidazo[4,5-b]pyridine (2l) was identified as a potent angiotensin II type I receptor blocker (IC{sub 50} = 1.6 nM) with partial PPAR{gamma} agonism (EC{sub 50} = 212 nM, 31% max) and oral bioavailability in rat. The dual pharmacology of 2l was demonstrated in animal models of hypertension (SHR) and insulin resistance (ZDF rat). In the SHR, 2l was highly efficacious in lowering blood pressure, while robust lowering of glucose and triglycerides was observed in the male ZDF rat.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Nutritional status and random blood glucose, cholesterol and triglyceride test among Malaysian Army (MA) personnel in Kuala Lumpur

With the rising trend of obesity among the general population, it is also important to assess the obesity and health status among military population. The aim of this study was to determine the prevalence of overweight and obesity among Malaysian Army (MA) personnel as well as the relationship between selected socio-demographics factors, antropometric profiles, body composition and random blood test value. A cross sectional study involving 378 male military personnel aged between 20 to 48 years old was conducted at two MA bases in Kuala Lumpur between November and December 2012. Antropometric measurements included height, weight and waist circumference (WC). Body fat percentage was measured using bioelectrical impedance analysis method (Tanita TBF-300A). Mean height, weight, BMI, WC, body fat percentage, age, monthly income and duration of service were 1.71 ± 0.6 m, 71.7 ± 12.2 kg, 24.6 ± 4.1 kg/m{sup 2}, 87.0 ± 10.0 cm, 23.4 ± 6.6%, 29.1 ± 5.5 years, RM 2115.12 ± 860.70 and 9.9 ± 5.6 years respectively. According to WHO (1998) classification of BMI, 3.2% of the subjects were underweight, 54.8% normal, 32.8% overweight and 9.3% obese. It was obeserved that 40.2% of the subjects had waist circumference value of 90 cm or more and were considered high risk for diebetes and cardiovascular diseases. This study found that BMI was highly correlated with weight (r=0.925, p<0.05), WC (r=0.852, p<0.05) and body fat percentage. Body fat percentage also show high correlation with weight (r=0.759, p<0.05) and WC (r=0.768, p<0.05. The result from 173 of 378 subjects that were selected for random blood test found that 4.6%, 3.5% and 26.0% had diabetes, high cholesterol and high triglyceride respectively. There was a weak correlation between random blood glucose level with weight (r=0.221, p<0.05), BMI (r=0.243, p<0.05), WC (r=0.298, p<0.05), body fat percentage (r=0.163, p<0.05) and age (r=0.223, p<0.05). Random blood cholesterol level had significant correlation with weight (r=0.284, p<0.05), BMI (r=0.260, p<0.05), WC (r=0.362, p<0.05) and body fat percentage (r=0.313, p<0.05). It was also noted that random blood triglyceride level was significantly correlated with weight (r=0.223, p<0.05), BMI (r=0.312, p<0.05), WC (r=0.288, p<0.05), body fat percentage (r=0.287, p<0.05) and age (r=0.268 p<0.05). These results call for attention to the existence of overweight and obesity as well as the risk of non-communicable diseases among military population. Therefore, future intervention from the aspect of nutritional education and health awareness can benefit thus optimizing the health status of MA military personnel.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Difference between healthy children and ADHD based on wavelet spectral analysis of nuclear magnetic resonance images

The main goal of this project was to create a computer algorithm based on wavelet analysis of region of homogeneity images obtained during resting state studies. Ideally it would automatically diagnose ADHD. Because the cerebellum is an area known to be affected by ADHD, this study specifically analysed this region. Male right handed volunteers (infants with ages between 7 and 11 years old) were studied and compared with age matched controls. Statistical differences between the values of the absolute integrated wavelet spectrum were found and showed significant differences (p<0.0015) between groups. This difference might help in the future to distinguish healthy from ADHD patients and therefore diagnose ADHD. Even if results were statistically significant, the small size of the sample limits the applicability of this methods as it is presented here, and further work with larger samples and using freely available datasets must be done.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Peripheral white blood cells profile of biodegradable metal implant in mice animal model

Biocompatibility or safety of the medical device is considered important. It can be determined by blood profile examination. The aim of this study was to assess the biocompatibility of biodegradable metal implant through peripheral white blood cells (WBCs) profile approach. Forty eight male ddy mice were divided into four groups according to the materials implanted: iron wire (Fe), magnesium rod (Mg), stainless steel surgical wire (SS316L) and control with sham (K). Implants were inserted and attached onto the right femoral bone on latero-medial region. In this study, peripheral white blood cells and leukocyte differentiation were the parameters examined. The result showed that the WBCs value of all groups were decreased at the first day after implantation, increased at the 10th day and continued increasing at the 30th day of observation, except Mg group which has decreased. Neutrophil, as an inflammatory cells, was increased at the early weeks and decreased at the day-30 after surgery in all groups. Despite, these values during the observation were still within the normal range. As a conclus ion, biodegradable metal implants lead to an inflammatory reaction, with no adverse effect on WBC value found.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Laser speckle contrast imaging of cerebral autoregulation in rats at a macro- and microcirculation level

Using the method of laser speckle imaging for the simultaneous study of macro- and microcirculation in cerebral vessels of healthy rats, we show that the mechanisms underlying cerebral autoregulation depend on the initial condition of the organism and the sex of individual animals. The pharmacological dose-dependent stimulation of the peripheral arterial pressure increase is not accompanied by the cerebral circulation responses of analogous intensity, but manifests itself as 'compensating' reactions, namely, the redistribution of the blood flow at the level of macro- (in females) and microcirculation (in females and males). The obtained results extend our understanding of the capabilities of laser speckle imaging technique in neurophysiological studies of reserve abilities of cerebral circulation autoregulation under the conditions of hypertensive status formation. (laser biophotonics)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Describing patterns of familial cancer risk in subfertile men using population pedigree data

STUDY QUESTION Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? SUMMARY ANSWER Here, distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. WHAT IS KNOWN ALREADY Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. STUDY DESIGN, SIZE, DURATION A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966–2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS Azoospermic (0 × 10 6 /mL) and severely oligozoospermic (<1.5 × 10 6 /mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966–2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. MAIN RESULTS AND THE ROLE OF CHANCE Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48–4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01–2.39), uterine cancers HR = 1.27 (95% CI = 1.03–1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07–2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21–1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01–1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30–4.54), and testis cancer HR = 2.34 (95% CI = 1.60–3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16–0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96–2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64–12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1–3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19–2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84–9.32). LIMITATIONS, REASONS FOR CAUTION Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. WIDER IMPLICATIONS OF THE FINDINGS This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Let’s talk about sex: A biological variable in immune response against melanoma

As science culture gravitates toward a more holistic inclusion of both males and females in research design, the outlining of sex differences and their respective intersections with disease physiology and pathophysiology should see reciprocal expansion. Melanoma skin cancer, for example, has observed a female advantage in incidence, mortality, and overall survival since the early 1970s. The exact biological mechanism of this trend, however, is unclear and further complicated by a layering of clinical variables such as skin phototype, age, and body mass index. In this perspective, we highlight epidemiological evidence of sex differences in melanoma and summarize the landscape of their potential origin. Among several biological hallmarks, we make a note of sex-specific immune profiles—along with divergent hormonal regulation, social practices, DNA damage and oxidative stress responses, body composition, genetic variants, and X-chromosome expression—as probable drivers of disparity in melanoma initiation and progression. This review further focuses the conversation of sex as an influencing factor in melanoma development and its potential implication for disease management and treatment strategies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sites

Purpose: The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations. Methods: The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotal skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). Results: The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035-2.71 Gy) and 0.34 Gy (range, 0.066-3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03-0.159 Gy) and 0.05 Gy (range, 0.015-0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056-1.97 Gy) and 0.306 Gy (range, 0.065-2.25 Gy). Conclusions: Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-J-86: Lobar Lung Function Quantification by PET Galligas and CT Ventilation Imaging in Lung Cancer Patients

Purpose: The purpose of this study was to quantify the lobar lung function using the novel PET Galligas ([68Ga]-carbon nanoparticle) ventilation imaging and the investigational CT ventilation imaging in lung cancer patients pre-treatment. Methods: We present results on our first three lung cancer patients (2 male, mean age 78 years) as part of an ongoing ethics approved study. For each patient a PET Galligas ventilation (PET-V) image and a pair of breath hold CT images (end-exhale and end-inhale tidal volumes) were acquired using a Siemens Biograph PET CT. CT-ventilation (CT-V) images were created from the pair of CT images using deformable image registration (DIR) algorithms and the Hounsfield Unit (HU) ventilation metric. A comparison of ventilation quantification from each modality was done on the lobar level and the voxel level. A Bland-Altman plot was used to assess the difference in mean percentage contribution of each lobe to the total lung function between the two modalities. For each patient, a voxel-wise Spearmans correlation was calculated for the whole lungs between the two modalities. Results: The Bland-Altman plot demonstrated strong agreement between PET-V and CT-V for assessment of lobar function (r=0.99, p<0.001; range mean difference: −5.5 to 3.0). The correlation between PET-V and CT-V at the voxel level was moderate(r=0.60, p<0.001). Conclusion: This preliminary study on the three patients data sets demonstrated strong agreement between PET and CT ventilation imaging for the assessment of pre-treatment lung function at the lobar level. Agreement was only moderate at the level of voxel correlations. These results indicate that CT ventilation imaging has potential for assessing pre-treatment lobar lung function in lung cancer patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Effect of respiratory motion on internal radiation dosimetry

Purpose: Estimation of the radiation dose to internal organs is essential for the assessment of radiation risks and benefits to patients undergoing diagnostic and therapeutic nuclear medicine procedures including PET. Respiratory motion induces notable internal organ displacement, which influences the absorbed dose for external exposure to radiation. However, to their knowledge, the effect of respiratory motion on internal radiation dosimetry has never been reported before. Methods: Thirteen computational models representing the adult male at different respiratory phases corresponding to the normal respiratory cycle were generated from the 4D dynamic XCAT phantom. Monte Carlo calculations were performed using the MCNP transport code to estimate the specific absorbed fractions (SAFs) of monoenergetic photons/electrons, the S-values of common positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y-86, and I-124), and the absorbed dose of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) in 28 target regions for both the static (average of dynamic frames) and dynamic phantoms. Results: The self-absorbed dose for most organs/tissues is only slightly influenced by respiratory motion. However, for the lung, the self-absorbed SAF is about 11.5% higher at the peak exhale phase than the peak inhale phase for photon energies above 50 keV. The cross-absorbed dose is obviously affected by respiratory motion for many combinations of source-target pairs. The cross-absorbed S-values for the heart contents irradiating the lung are about 7.5% higher in the peak exhale phase than the peak inhale phase for different positron-emitting radionuclides. For {sup 18}F-FDG, organ absorbed doses are less influenced by respiratory motion. Conclusions: Respiration-induced volume variations of the lungs and the repositioning of internal organs affect the self-absorbed dose of the lungs and cross-absorbed dose between organs in internal radiation dosimetry. The dynamic anatomical model provides more accurate internal radiation dosimetry estimates for the lungs and abdominal organs based on realistic modeling of respiratory motion. This work also contributes to a better understanding of model-induced uncertainties in internal radiation dosimetry.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Placebo-resistant gut bacteria: Akkermansia muciniphila spp. and Familial Mediterranean fever disease

Introduction: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved. Methods: This study represents the in augural analysis of the placebo’s influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835. Results and Discussion: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among “healthy” gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2004

Postflight balance control recovery in an elderly astronaut: a case report

OBJECTIVE: To examine the sensorimotor adaptive response of a 77-year-old man exposed to the gravito-inertial challenges of orbital space flight. STUDY DESIGN: Prospective case study with retrospective comparisons. SETTING: NASA Neurosciences Laboratory (Johnson Space Center) and Baseline Data Collection Facility (Kennedy Space Center). PRIMARY PARTICIPANT: One 77-year-old male shuttle astronaut. INTERVENTION: Insertion into low Earth orbit was used to remove gravitational stimuli and thereby trigger sensorimotor adaptation to the microgravity environment. Graviceptor stimulation was reintroduced at landing, and sensorimotor readaptation to the terrestrial environment was tracked to completion. MAIN OUTCOME MEASURES: Computerized dynamic posturography tests were administered before and after orbital flight to determine the magnitude and time course of recovery. RESULTS: The elderly astronaut exhibited balance control performance decrements on landing day; however, there were no significant differences between his performance and that of younger astronauts tested on the same shuttle mission or on previous shuttle missions of similar duration. CONCLUSIONS: These results demonstrate that the physiological changes attributed to aging do not necessarily impair adaptive sensorimotor control processes.

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