Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “FATS”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Saturation of SERCA's lipid annulus may protect against its thermal inactivation

The sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA) pumps are integral membrane proteins that catalyze the active transport of Ca{sup 2+} into the sarcoplasmic reticulum, thereby eliciting muscle relaxation. SERCA pumps are highly susceptible to oxidative damage, and cytoprotection of SERCA dampens thermal inactivation and is a viable therapeutic strategy in combating diseases where SERCA activity is impaired, such as muscular dystrophy. Here, we sought to determine whether increasing the percent of saturated fatty acids (SFA) within SERCA's lipid annulus through diet could protect SERCA pumps from thermal inactivation. Female Wistar rats were fed either a semi-purified control diet (AIN93G, 7% soybean oil by weight) or a modified AIN93G diet containing high SFA (20% lard by weight) for 17 weeks. Soleus muscles were extracted and SERCA lipid annulus and activity under thermal stress were analyzed. Our results show that SERCA's lipid annulus is abundant with short-chain (12–14 carbon) fatty acids, which corresponds well with SERCA's predicted bilayer thickness of 21 Å. Under control-fed conditions, SERCA's lipid annulus was already highly saturated (79%), and high-fat feeding did not increase this any further. High-fat feeding did not mitigate the reductions in SERCA activity seen with thermal stress; however, correlational analyses revealed significant and strong associations between % SFA and thermal stability of SERCA activity with greater %SFA being associated with lower thermal inactivation and greater % polyunsaturation and unsaturation index being associated with increased thermal inactivation. Altogether, these findings show that SERCA's lipid annulus may influence its susceptibility to oxidative damage, which could have implications in muscular dystrophy and age-related muscle wasting. - Highlights: • SERCA's lipid annulus in rat soleus was measured after immunoconcentration. • Short fatty acid chains surround SERCA and may ensure optimal hydrophobic matching. • SERCA's annulus is highly saturated in control-fed and high-fat fed rats. • Greater saturation associates with small levels of thermal inactivation. • Greater unsaturation associates with large levels of thermal inactivation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage prepubertally. ► E2 appears as an endocrine disruptor that might contribute to childhood obesity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Oleic acid and glucose regulate glucagon-like peptide 1 receptor expression in a rat pancreatic ductal cell line

The glucagon-like peptide 1 receptor (GLP1R) plays a critical role in glucose metabolism and has become an important target for a growing class of drugs designed to treat type 2 diabetes. In vitro studies were designed to investigate the effect of the GLP1R agonist, exenatide (Ex4), in “on-target” RIN-5mF (islet) cells as well as in “off-target” AR42J (acinar) and DSL-6A/C1 (ductal) cells in a diabetic environment. Ex4 increased islet cell proliferation but did not affect acinar cells or ductal cells at relevant concentrations. A high caloric, high fat diet is a risk factor for impaired glucose tolerance and type-2 diabetes. An in vitro Oleic acid (OA) model was used to investigate the effect of Ex4 in a high calorie, high fat environment. At 0.1 and 0.4 mM, OA mildly decreased the proliferation of all pancreatic cell types. Ex4 did not potentiate the inhibitory effect of OA on cell proliferation. Akt phosphorylation in response to Ex4 was diminished in OA-treated ductal cells. GLP1R protein detected by western blot was time and concentration dependently decreased after glucose stimulation in OA-treated ductal cells. In ductal cells, OA treatment altered the intracellular localization of GLP1R and its co-localization with early endosome and recycling endosomes. Chloroquine (lysosomal inhibitor), N-acetyl-L-cysteine (reactive oxygen species scavenger) and wortmannin (a phosphatidylinositol-3-kinase inhibitor), fully or partially, rescued GLP1R protein in OA-pretreated, glucose-stimulated ductal cells. The impact of altered regulation on phenotype/function is presently unknown. However, these data suggest that GLP1R regulation in ductal cells can be altered by a high fat, high calorie environment. -- Highlights: ► Exenatide did not inhibit islet, acinar or ductal cell proliferation. ► GLP1R protein decreased after glucose stimulation in oleic acid-treated ductal cells. ► Oleic acid treatment altered localization of GLP1R with early and recycling endosomes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P{sub 450} enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. -- Highlights: ► Vitamin E-atorvastatin interactions were studied in hypercholesterolemic guinea pigs. ► High-dose α-tocopherol did not alter the lipid-lowering efficacy of atorvastatin. ► α-Tocopherol did not change the expression of CYP3A4, CYP4F2, CYP20A or OATP C. ► α-Tocopherol did not affect phase I metabolism of atorvastatin. ► Vitamin E does not change atorvastatin pharmacodynamics or toxicity in guinea pigs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced Cyp2b10 and Cyp3a11 (CAR/PXR target genes) • Aroclor 1260 at 200 mg/kg induced Cyp1a2 (AhR target gene)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet. • Genistein modulation of neutrophils is associated with blood glucose levels.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153

Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000 pg/kg body weight/day; PCB 153: 0.09–1406 μg/kg body weight/d). Then exposure was ceased and offspring were followed up to 1 year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes. - Highlights: • Early life exposure to TCDD affects programming of energy and immune homeostasis. • Early life exposure to PCB 153 affects programming of energy homeostasis. • Both compounds act sex-specifically. • Lowest derived BMDLs for both TCDD and PCB 153 are not lower than current tolerable daily intakes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

MO-G-17A-03: MR-Based Cortical Bone Segmentation for PET Attenuation Correction with a Non-UTE 3D Fast GRE Sequence

Purpose: To determine the feasibility of identifying cortical bone on MR images with a short-TE 3D fast-GRE sequence for attenuation correction of PET data in PET/MR. Methods: A water-fat-bone phantom was constructed with two pieces of beef shank. MR scans were performed on a 3T MR scanner (GE Discovery™ MR750). A 3D GRE sequence was first employed to measure the level of residual signal in cortical bone (TE{sub 1}/TE{sub 2}/TE{sub 3}=2.2/4.4/6.6ms, TR=20ms, flip angle=25°). For cortical bone segmentation, a 3D fast-GRE sequence (TE/TR=0.7/1.9ms, acquisition voxel size=2.5×2.5×3mm{sup 3}) was implemented along with a 3D Dixon sequence (TE{sub 1}/TE{sub 2}/TR=1.2/2.3/4.0ms, acquisition voxel size=1.25×1.25×3mm{sup 3}) for water/fat imaging. Flip angle (10°), acquisition bandwidth (250kHz), FOV (480×480×144mm{sup 3}) and reconstructed voxel size (0.94×0.94×1.5mm{sup 3}) were kept the same for both sequences. Soft tissue and fat tissue were first segmented on the reconstructed water/fat image. A tissue mask was created by combining the segmented water/fat masks, which was then applied on the fast-GRE image (MRFGRE). A second mask was created to remove the Gibbs artifacts present in regions in close vicinity to the phantom. MRFGRE data was smoothed with a 3D anisotropic diffusion filter for noise reduction, after which cortical bone and air was separated using a threshold determined from the histogram. Results: There is signal in the cortical bone region in the 3D GRE images, indicating the possibility of separating cortical bone and air based on signal intensity from short-TE MR image. The acquisition time for the 3D fast-GRE sequence was 17s, which can be reduced to less than 10s with parallel imaging. The attenuation image created from water-fat-bone segmentation is visually similar compared to reference CT. Conclusion: Cortical bone and air can be separated based on intensity in MR image with a short-TE 3D fast-GRE sequence. Further research is required to optimize the strategy to reduce Gibbs artifacts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-I-62: Reduction of Susceptibility Artifacts by Increasing the Bandwidth (BW) and Echo Train Length (ETL)

Purpose: The aim of this present study is to increase bandwidth (BW) and echo train length (ETL) in Proton Density Turbo Spin Echo (PD TSE) sequences with and without fat saturation (FS) as well as in Turbo Inversion Recovery Magnitude sequences (TIRM) in order to assess whether these sequences are capable of reducing susceptibility artifacts. Methods: We compared 1) TIRM coronal (COR) with the same sequence with increased both BW and ETL 2) Conventional PD TSE sagittal (SAG) with FS with an increased BW 3) Conventional PD TSE SAG without FS with an increased BW 4) Conventional PD TSE SAG without FS with increased both BW and ETL. A quantitative analysis was performed to measure the extent of the susceptibility artifacts. Furthermore, a qualitative analysis was performed by two radiologists in order to evaluate the susceptibility artifacts, image distortion and fat suppression. The depiction of cartilage, menisci, muscles, tendons and bone marrow were also qualitatively analyzed. Results: The quantitative analysis found that the modified TIRM sequence is significantly superior to the conventional one regarding the extent of the susceptibility artifacts. In the qualitative analysis, the modified TIRM sequence was superior to the corresponding conventional one in eight characteristics out of ten that were analyzed. The modified PD TSE with FS was superior to the corresponding conventional one regarding the susceptibility artifacts, image distortion and depiction of bone marrow and cartilage while achieving effective fat saturation. The modified PD TSE sequence without FS with a high (H) BW was found to be superior corresponding to the conventional one in the case of cartilage. Conclusion: Consequently, TIRM sequence with an increased BW and ETL is proposed for producing images of high quality and modified PD TSE with H BW for smaller metals, especially when FS is used.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

TU-AB-201-11: A Novel Theoretical Framework for MRI-Only Image Guided LDR Prostate and Breast Brachytherapy Implant Dosimetry

Purpose: To propose a novel framework for accurate model-based dose calculations using only MR images for LDR prostate and breast seed implant brachytherapy. Methods: Model-based dose calculation methodologies recommended by TG-186 require further knowledge about specific tissue composition, which is challenging with MRI. However, relying on MRI-only for implant dosimetry would reduce the soft tissue delineation uncertainty, costs, and uncertainties associated with multi-modality registration and fusion processes. We propose a novel framework to address this problem using quantitative MRI acquisitions and reconstruction techniques. The framework includes three steps: (1) Identify the locations of seeds(2) Identify the presence (or absence) of calcification(s)(3) Quantify the water and fat content in the underlying tissueSteps (1) and (2) consider the sources that limit patient dosimetry, particularly the inter-seed attenuation and the calcified regions; while step (3) targets the quantification of the tissue composition to consider the heterogeneities in the medium. Our preliminary work has shown that the seeds and the calcifications can be identified with MRI using both the magnitude and the phase images. By employing susceptibility-weighted imaging with specific post-processing techniques, the phase images can be further explored to distinguish the seeds from the calcifications. Absolute quantification of tissue, water, and fat content is feasible and was previously demonstrated in phantoms and in-vivo applications, particularly for brain diseases. The approach relies on the proportionality of the MR signal to the number of protons in an image volume. By employing appropriate correction algorithms for T1 - and T2*-related biases, B1 transmit and receive field inhomogeneities, absolute water/fat content can be determined. Results: By considering calcification and interseed attenuation, and through the knowledge of water and fat mass density, accurate patient-specific implant dosimetry can be achieved with MRI-only. Conclusion: The proposed framework showed that model-based dose calculation is feasible using MRI-only state-of-the-art techniques.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TU-AB-BRA-01: Abdominal Synthetic CT Generation in Support of Liver SBRT Dose Calculation

Purpose: To demonstrate and validate a technique for generating MRI-derived synthetic CT volumes (MRCTs) in support of adaptive liver SBRT. Methods: Under IRB approval, ten hepatocellular carcinoma patients were scanned using a single MR sequence (T1 Dixon-VIBE), yielding inherently-registered water, fat, and T1-weighted images. Air-containing voxels were identified by intensity thresholding. The envelope of the anterior vertebral bodies was segmented from the fat image by fitting a shape model to vertebral body candidate voxels, then using level sets to expand the contour outward. Fuzzy-C-Means (FCM) was then used to classify each non-air voxel in the image as fat, water, bone, or marrow. Bone and marrow only were classified within the vertebral body envelope. The MRCT was created by integrating the product of the FCM class probability with the assigned class density for each voxel. The resulting MRCTs were deformably aligned with planning CTs and 2-ARC SBRT VMAT plans were optimized on the MRCT density maps. Fluence was copied onto the CT density grids and dose recalculated. Results: The MRCTs faithfully reproduced most of the features visible in the corresponding CT image volumes, with exceptions of ribs and posterior spinous processes. The liver, vertebral bodies, kidneys, spleen and cord all had median HU differences of less than 75 between MRCT and CT images. PTV D99% values had an average 0.2% difference (standard deviation: 0.46%) between calculations on MRCT and CT density grids. The maximum difference in dose to 0.1cc of the PTV was 0.25% (std:0.49%). OAR dose differences were similarly small (mean:0.03Gy, std:0.26Gy). The largest normal tissue complication percentage (NTCP) difference was 1.48% (mean:0.06%, std:0.54%). Conclusions: MRCTs from a single abdominal imaging sequence are promising for use in SBRT dose calculation. Future work will focus on extending models to better define bones in the upper abdomen. Supported by NIHR01EB016079 and NIH1L30CA199594-01.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Mongooses ( Urva auropunctata ) as reservoir hosts of Leptospira species in the United States Virgin Islands, 2019–2020

During 2019–2020, the Virgin Islands Department of Health investigated potential animal reservoirs of Leptospira spp., the bacteria that cause leptospirosis. In this cross-sectional study, we investigated Leptospira spp. exposure and carriage in the small Indian mongoose (Urva auropunctata, syn: Herpestes auropunctatus), an invasive animal species. This study was conducted across the three main islands of the U.S. Virgin Islands (USVI), which are St. Croix, St. Thomas, and St. John. We used the microscopic agglutination test (MAT), fluorescent antibody test (FAT), real-time polymerase chain reaction (lipl32 rt-PCR), and bacterial culture to evaluate serum and kidney specimens and compared the sensitivity, specificity, positive predictive value, and negative predictive value of these laboratory methods. Mongooses (n = 274) were live-trapped at 31 field sites in ten regions across USVI and humanely euthanized for Leptospira spp. testing. Bacterial isolates were sequenced and evaluated for species and phylogenetic analysis using the ppkgene. Anti-Leptospira spp. antibodies were detected in 34% (87/256) of mongooses. Reactions were observed with the following serogroups: Sejroe, Icterohaemorrhagiae, Pyrogenes, Mini, Cynopteri, Australis, Hebdomadis, Autumnalis, Mankarso, Pomona, and Ballum. Of the kidney specimens examined, 5.8% (16/270) were FAT-positive, 10% (27/274) were culture-positive, and 12.4% (34/274) were positive by rt-PCR. Of the Leptospira spp. isolated from mongooses, 25 were L. borgpetersenii, one was L. interrogans, and one was L. kirschneri. Positive predictive values of FAT and rt-PCR testing for predicting successful isolation of Leptospira by culture were 88% and 65%, respectively. The isolation and identification of Leptospira spp. in mongooses highlights the potential role of mongooses as a wildlife reservoir of leptospirosis; mongooses could be a source of Leptospira spp. infections for other wildlife, domestic animals, and humans.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Body surface area equations for physically active men and women

Abstract Objectives To improve predictive formulae for estimating body surface area (BSA) in healthy men and women using a modern three‐dimensional scanner technology. Methods Body surface areas were obtained from a convenience sample of 1267 US Marines (464 women and 803 men) using a whole body surface scanner (Size Stream SS20). The reliability of SS20 measures of total and regional BSA within participants was compared across triplicate scans. We then derived a series of formulae to estimate SS20‐measured BSA using various combinations of sex, height, and mass. We also assessed relationships between percent body fat measured by dual‐energy x‐ray absorptiometry and sex‐specific formulae errors in Marines. Results Body surface areas recorded by the SS20 were highly reliable whether measured for the total body or by region (ICC ≥ .962). Formulae estimates of BSA from sex, height, and mass were precise (root‐mean‐square deviation, 0.031 m 2 ). Errors from the Marine Corps formulae were positively associated with percent body fat for men ( p = .001) but not women ( p = .843). Conclusions Clinicians, military leaders, and researchers can use the newly developed BSA formulae for precise estimates in healthy physically active men and women. Users should be aware that height‐ and mass‐based BSA estimates are less accurate for individuals with extremely low or high percent body fat.

Looney, David P.↗
DOE OSTI2010

Is 3T-MR Spectroscopy a Predictable Selection Tool in Prophylactic Vertebroplasty?

This study was designed to confirm relationships between decrease of bone mineral density and increase of marrow fat and to delineate, through MR spectroscopy, vertebral body at high risk for compression fracture onset to justify prophylactic vertebroplasty. We enrolled 127 women: 48 osteoporotic, 36 osteopenic, and 43 normal subjects, who underwent DXA and MR examination of spine. Then, we selected 48 patients with at least two acute osteoporotic vertebral fractures with interposed normal 'sandwich' vertebrae; all patients underwent MR examination of spine. Significant statistical differences were found among 'Fat Fraction' (FF) values in normal, osteopenic, and osteoporotic subjects: 59.8 {+-} 5.1%; 64.8 {+-} 4.4%; and 67.1 {+-} 3.3%. A mild, significant, negative correlation was observed between T-score and vertebral fat content (r = - 0.585; P = 0.0000). In the second part of the study, 9 new vertebral fractures were observed in 48 patients (19%): 6 were 'sandwich' vertebrae (12.5%), and 3 were located in distant vertebral body. The mean FF in sandwich fractured vertebrae was 72.75 {+-} 1.95 compared with the FF of the nonfractured sandwich, and distant control vertebrae were 61.83 {+-} 3.42 and 61.42 {+-} 3.64. We found a significant statistical difference between fractured and nonfractured vertebrae (P < 0.001). The results of this study suggest that MR spectroscopy could be a reliable index to predict the risk of new compression vertebral fracture and could be used for vertebroplasty planning contributing to clarify the possibility to add prophylactic PVP to standard treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Fatty acid oxidation alleviates the energy deficiency caused by the loss of MPC1 in MPC1+/− mice

Highlights: • The MPC1{sup +/−} mice model shows energy deficiency. • The deficiency caused by the loss of MPC1 alleviated by given high fat diet. • Fatty acid oxidation provides energy to sustain energy requirement. Pyruvate is a central substrate in energy metabolism, paramount to carbohydrate, fat, and amino acid catabolic and anabolic pathways. Mitochondrial pyruvate carrier 1(MPC1) is one important component of the complex that facilitates mitochondrial pyruvate import. Complete MPC1 deficiency is a serious concern, and has been shown to result in embryonic lethality in mice. The study outlined in this paper generated one mouse line with the MPC1 protein part deficiency by using the CRISPR/Cas9 system. Clinical observations, body weight and organ/tissue weight, gas exchange, cold-stimulation, blood parameters, as well as histopathology analysis were analyzed to evaluate potential physiological abnormalities caused by MPC1 deficiency. Results indicate that MPC1{sup +/−} mice experienced a change in important clinical criteria such as low body weight, decreased movement, and low body shell temperature, few adipose accumulate. The mice show significant difference in some blood parameters including apo-B100, apo-A1, HDL, glucagon, insulin. However these changes alleviated while being fed with the HFD, which provided metabolites to sustain the TCA cycle and body development. The MPC1{sup +/−} mice may employ fatty acid oxidation to meet their bioenergetic demands. This study suggests that inhibition of MPC1 activity can boost fatty acid oxidation to provide sufficient energy to the body. This work promotes further studies regarding the interplay between carbohydrate and fat metabolism.

60 APPLIED LIFE SCIENCES↗