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At least 595 records · Page 33

Nutrition-Responsive Glia Control Exit of Neural Stem Cells from Quiescence

The systemic regulation of stem cells ensures that they meet the needs of the organism during growth and in response to injury. A key point of regulation is the decision between quiescence and proliferation. During development, Drosophila neural stem cells (neuroblasts) transit through a period of quiescence separating distinct embryonic and postembryonic phases of proliferation. It is known that neuroblasts exit quiescence via a hitherto unknown pathway in response to a nutrition-dependent signal from the fat body. We have identified a population of glial cells that produce insulin/IGF-like peptides in response to nutrition, and we show that the insulin/IGF receptor pathway is necessary for neuroblasts to exit quiescence. The forced expression of insulin/IGF-like peptides in glia, or activation of PI3K/Akt signaling in neuroblasts, can drive neuroblast growth and proliferation in the absence of dietary protein and thus uncouple neuroblasts from systemic control.

59 BASIC BIOLOGICAL SCIENCES↗

Effect of the ..beta..-Hydroxy Group on Ester Reactivity: Combustion Kinetics of Methyl Hexanoate and Methyl 3-Hydroxyhexanoate

One of the major biofuels used today is biodiesel, composed of fatty acid methyl esters. The fats and oils feedstocks used to make biodiesel are in relatively short supply. To meet increasing global demand, engineered microorganisms have been developed to catalyze conversion of sugar to fatty acid esters that contain unique ..beta..-hydroxy-esters. This study investigated the effect of a hydroxyl group on the combustion characteristics of methyl esters by comparing the chemical behavior of methyl hexanoate (MHx) and methyl 3-hydroxyhexanoate (M3OHHx) - used as surrogates for diesel-boiling-range esters with longer fatty acid chains. The oxidation of these esters was studied experimentally in a flow reactor at 0.84 and 10 bar, 600 to 1,100 K, and stoichiometric conditions; and in a constant volume combustion chamber at 5 and 10 bar, 600 to 900 K, and equivalence ratios of 0.3 and 0.6. MHx was more reactive in the constant volume chamber at temperatures below 800 K at 10 bar and equivalence ratio of 0.6. MHx also exhibited a higher indicated cetane number (16.4) than M3OHHx (8.1). We investigated this reactivity trend using an updated MHx kinetic model and M3OHHx model developed as part of this work. The kinetic models predicted that radicals formed from MHx were consumed by low-temperature chemistry reactions, whereas the M3OHHx reactivity was significantly governed by the ..beta..-radical (on the same carbon as the OH group) chemistry which mainly terminated via the less reactive chain propagation pathway to methyl-3-oxohexanoate + HO2. This study extends our understanding of structural effects on ester reactivity, which will allow for accurate surrogate formulation and performance simulations.

AFIDA↗

Genetically pliable green algae for bioproduction of modified fatty acids, nutritional therapeutic oils, and biopharmaceuticals

Homologous recombination (HR) is an essential tool for complex metabolic engineering in yeast, but transgene integration into plant and green algal nuclear genomes predominantly occurs by non-homologous end-joining. Species of the closely related, oleaginous trebouxiophytes Auxenochlorella and Prototheca, are unusual among the green algae in that HR is the favored mechanism for DNA integration into the nuclear genome. This property enables locus-specific targeting of gene cassettes encoding multiple enzymes for manipulating existing biochemical pathways or introducing new functions. Genetic malleability, and regulatory approval for human consumption, coupled with robust fermentation performance at industrial scale, establishes Auxenochlorella and Prototheca as prime candidates for algal production of biochemicals and biomaterials. The examples presented here highlight strain improvement and engineering for synthesis of hydroxylated fatty acids for biomaterials, structured triglycerides resembling human milk fat for infant nutrition, very-long-chain mono- and polyunsaturated fatty acids with nutraceutical or therapeutic potential, and cannabinoids for pharmacological applications.

Moseley, Jeffrey L. [University of California, Ber↗

Biofuel production from palm oil deoxygenation using nickel-molybdenum on zirconia catalyst using glycerol as a hydrogen donor

The growing demand for renewable energy has generated interest in biofuels as alternatives to fossil fuels. Second-generation biofuels, derived from deoxygenating fats and oils, have garnered a higher level of interest from industry and academia due to their potential for direct replacement of diesel and jet fuels. Palm oil, mostly cultivated in Thailand and composed of C16 and C18 fatty acids, is a primary feedstock sought for biofuel production. Palm oil deoxygenation contains several pathways that may or may not require hydrogen gas. This study aimed to produce biofuels in different fuel ranges, such as gasoline, jet fuel, and diesel, through palm oil deoxygenation using glycerol as a hydrogen source. Glycerol, a low-value byproduct, was used as a hydrogen donor, whereas nickel-molybdenum-supported catalysts were chosen for their high efficiency in deoxygenation and cost-effectiveness. The study investigated the impact of reaction time, temperature, and catalyst activation method on palm oil deoxygenation. Catalyst characterization methods, including XRD, SEM, TEM, XPS, FTIR, TGA, and nitrogen-sorption, were employed to understand the role of catalysts’ activity during palm oil upgrading. Findings indicated that alkane hydrocarbons are the major components in liquid products. The presence of excess hydrogen in post reaction gaseous phase proves the hydrogen donation capability of glycerol. Increased reaction time and temperature facilitated the removal of oxygen from palm oil. Nickel-molybdenum on zirconia activated by sulfidation demonstrated higher stability than by reduction activation.

09 BIOMASS FUELS↗

Evaluation of Performance Variables to Accelerate the Deployment of Sustainable Aviation Fuels at a Regional Scale

An increase in jet fuel consumption and its associated emissions across the world have led to the need for alternative technologies to produce sustainable aviation fuels (SAF). One option to produce SAFs is to utilize waste or biomass-based feedstocks that has the potential to reduce greenhouse gas emissions by 50% or more compared to conventional jet fuel. However, there is a lack of understanding of how the synergistic effects of key performance variables could hinder or help the deployment of aviation fuels on a regional scale. Here, we assess the implications of key variables-including type and quantity of waste/biomass feedstock availability near the airport, cost of SAF production, life cycle greenhouse gas (GHG) emissions, policies, and fuel/infrastructure logistics-on the deployment of SAF at Chicago's O'Hare International Airport. We consider three ASTM International-approved SAF technologies (Hydroprocessed Esters and Fatty Acids, Fischer-Tropsch, and Alcohol to Jet) that can be blended up to 50% with petroleum-based jet fuel. Results from our analysis show that woody biomass-based Fischer-Tropsch technology has the lowest fuel production costs ($2.31-$2.81/gallon gasoline equivalent) of all pathways, and it reduces life cycle GHG emissions by 86% compared to conventional jet fuel despite the higher availability of crop residues compared to either woody biomass or fats, oils, and greases. Also, infrastructure is available at O'Hare International Airport to blend SAF with Jet A fuel through three terminals directly connected to the airport via pipelines. Our sensitivity analysis shows renewable fuel incentives and feedstock price to be key performance variables affecting the production cost and deployment of SAF.

alcohol-to-jet↗

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals—Depot differences and dysmetabolism implications

Background: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (R{sub S}=0.310, p<0.01) and duration of obesity (R{sub S}=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (R{sub S}=0.277, p<0.01), with relevance for vAT (R{sub S}=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens. - Highlights: • POPs are pervasive in this sample of obese patients undergoing bariatric surgery. • Distinct adipose tissues have dissimilar POPs storage capability. • Despite the presence of obesity, POPs are important for metabolic dysregulation.

54 ENVIRONMENTAL SCIENCES↗

Lower levels of Persistent Organic Pollutants, metals and the marine omega 3-fatty acid DHA in farmed compared to wild Atlantic salmon (Salmo salar)

Contaminants and fatty acid levels in farmed- versus wild Atlantic salmon have been a hot topic of debate in terms of food safety. The present study determined dioxins (polychlorinated dibenzo-p-dioxin and dibenzofuran), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), metals and fatty acids in wild and farmed Atlantic salmon. Contaminant levels of dioxins, PCBs, OCPs (DDT, dieldrin, lindane, chlordane, Mirex, and toxaphene), and mercury were higher in wild salmon than in farmed salmon, as were the concentrations of the essential elements selenium, copper, zinc and iron, and the marine omega-3 fatty acid docosahexaenoic acid (DHA). PBDE, endosulfan, pentachlorobenzene, hexachlorobenzene, cadmium and lead levels were low and comparable in both wild and farmed fish, and there was no significant difference in the marine omega-3 fatty acid eicosapentaenoic acid (EPA) concentration. The total fat content was significantly higher in farmed than wild salmon due to a higher content of both saturated and monounsaturated fatty acids, as well as a higher content of omega-6 fatty acids. The omega-3 to omega-6 fatty acid ratio was considerably lower in farmed than wild salmon due to the high level of omega-6 fatty acids. Contaminant concentrations in Atlantic salmon were well below maximum levels applicable in the European Union. Atlantic salmon, both farmed and wild, is a good source of EPA and DHA with a 200 g portion per week contributing 3.2 g or 2.8 g respectively, being almost twice the intake considered adequate for adults by the European Food Safety Authority (i.e. 250 mg/day or 1.75 g/week). - Highlights: • A comprehensive study of contaminants and nutrients in farmed- and wild Atlantic salmon. • Wild salmon had higher levels of persistent organic pollutants and mercury than farmed salmon. • Farmed salmon had higher levels of omega-6 fatty acids than wild salmon. • Farmed- and wild salmon had comparable levels of EPA, whereas farmed salmon had lower levels of DHA.

54 ENVIRONMENTAL SCIENCES↗

Fish energy budget under ocean warming and flame retardant exposure

Highlights: • Energy proportion spent for growth dominated the mode of energy allocation (56–68%). • Energy channelled for R was around 26%, followed by excretion (F: 4–16%; U: 2–3%). • Energy budget parameters were significantly affected by warming and BDE-209 exposure. • Higher levels occurred under warming conditions: for weight, protein, ash and RGR. • Higher levels occurred under both stressors: for FE, AER, RMR and K{sub 1}. Climate change and chemical contamination are global environmental threats of growing concern for the scientific community and regulatory authorities. Yet, the impacts and interactions of both stressors (particularly ocean warming and emerging chemical contaminants) on physiological responses of marine organisms remain unclear and still require further understanding. Within this context, the main goal of this study was to assess, for the first time, the effects of warming (+ 5 °C) and accumulation of a polybrominated diphenyl ether congener (BDE-209, brominated flame retardant) through dietary exposure on energy budget of the juvenile white seabream (Diplodus sargus). Specifically, growth (G), routine metabolism (R), excretion (faecal, F and nitrogenous losses, U) and food consumption (C) were calculated to obtain the energy budget. The results demonstrated that the energy proportion spent for G dominated the mode of the energy allocation of juvenile white seabream (56.0–67.8%), especially under the combined effect of warming plus BDE-209 exposure. Under all treatments, the energy channelled for R varied around 26% and a much smaller percentage was channelled for excretion (F: 4.3–16.0% and U: 2.3–3.3%). An opposite trend to G was observed to F, where the highest percentage (16.0 ± 0.9%) was found under control temperature and BDE-209 exposure via diet. In general, the parameters were significantly affected by increased temperature and flame retardant exposure, where higher levels occurred for: i) wet weight, relative growth rate, protein and ash contents under warming conditions, ii) only for O:N ratio under BDE-209 exposure via diet, and iii) for feed efficiency, ammonia excretion rate, routine metabolic rate and assimilation efficiency under the combination of both stressors. On the other hand, decreased viscerosomatic index was observed under warming and lower fat content was observed under the combined effect of both stressors. Overall, under future warming and chemical contamination conditions, fish energy budget was greatly affected, which may dictate negative cascading impacts at population and community levels. Further research combining other climate change stressors (e.g. acidification and hypoxia) and emerging chemical contaminants are needed to better understand and forecast such biological effects in a changing ocean.

54 ENVIRONMENTAL SCIENCES↗

Diphenyl diselenide regulates Nrf2/Keap-1 signaling pathway and counteracts hepatic oxidative stress induced by bisphenol A in male mice

Highlights: • BPA exposure induced hepatic oxidative stress in a sex-dependent manner in mice. • BPA exposure deregulates Nrf2/keap1 pathway in the mouse liver. • (PhSe){sub 2} reversed hepatic oxidative stress caused by BPA in male mice. • (PhSe){sub 2} modulates NrF2/keap1 pathway in male mice exposed to BPA. Bisphenol A (BPA) is a chemical toxicant that has deleterious effects on human. BPA causes oxidative stress in tissues, including the liver. Diphenyl diselenide (PhSe){sub 2} improves the antioxidant response via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein (keap 1) pathway in macrophage cells. In the present study, we investigated whether (PhSe){sub 2} counteracts hepatic oxidative stress induced by BPA in male and female Swiss mice. Three-week-old mice received by the intragastric (i.g.) route BPA (5 mg/kg) from 21st to 60th postnatal day (PND). At PND 61, the mice were treated with (PhSe){sub 2} (1 mg/kg, i.g.) for seven days. Parameters of hepatic damage and oxidative stress were determined in male and female mice. The results show that BPA increased the activity of aspartate aminotransferase in female mice, and in male mice the activity of alanine aminotranseferase was increased. Male and female mice had an increase in fat mass accumulation. Male mice showed an increase in hepatic oxidative damage of proteins and a decrease in non-enzymatic (ascorbic acid and non-protein thiol) and enzymatic (superoxide dismutase) defenses, which are consistent with oxidative stress status. Male mice were more susceptible than female mice to hepatic oxidative stress induced by BPA. BPA decreased Nrf2/Keap1 protein content in male mice. (PhSe){sub 2} reduced hepatic oxidative stress induced by BPA in male mice. Our results demonstrate that male mice were more susceptible to hepatic oxidative stress induced by BPA than female mice. (PhSe){sub 2} regulated Nrf2/Keap-1 signaling pathway and countered hepatic oxidative stress induced by BPA in male mice.

60 APPLIED LIFE SCIENCES↗

Persistent organic pollutants as predictors of increased FSH:LH ratio in naturally cycling, reproductive age women

Highlights: • Endocrine disrupting chemicals pose a threat to female fecundity and reproduction. • Examined organochlorines and a marker of ovarian responsivity, FSH:LH ratio. • Increasing concentrations of estrogenic PCBs predict FSH:LH ratio > 2. • PCB congeners related to airborne exposure are associated with FSH:LH ratio > 2. Although several recent studies suggest endocrine disrupting compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p′, DDE), and hexachlorobenzene (HCB), target different organs and systems in the body, their impact on female reproductive function in humans is not well characterized. We seek to determine the relationship between several known endocrine disrupting compounds and a marker of ovarian responsivity, the FSH:LH ratio (higher ratio indicates less ovarian responsivity). For this analysis, 169 naturally cycling women between 21 and 38 years of age completed interviews and had their blood drawn on day 3 of their menstrual cycle for analyses of toxicants, gonadal sex hormones (E{sub 2} and P{sub 4}), and gonadotropins (FSH and LH). PCB congeners were classified into five groups based on their environmental persistence, distribution in human tissue, and toxicological action, reflecting the structure, mechanism, and known biological activity of individual PCB congeners. For every unit (ppb) increase in the level of the estrogenic PCB group, there was a 5-fold greater risk of a FSH:LH ratio ≥ 2, controlling for individual differences in age, percent body fat, cycle day 3 estradiol levels, parity, alcohol use and cigarette smoking in the past year (exp[ß] = 5; p = ≤0.01). PCB congeners identified as estrogenic were analyzed individually, and, of the 19 potentially estrogenic congeners, five were significantly, and positively related to an increased FSH:LH ratio. Four of these congeners are non-persistent, easily volatilize in the environment, and are easily metabolized, and hence, are indicative of very recent or current exposure. p,p′-DDE and HCB were not associated with FSH:LH ratio. We find a clinical indicator of ovarian responsivity, FSH:LH ratio, is associated with a specific group of estrogenic PCBs. These congeners may become airborne when they volatilize from dredged PCB-contaminated soil or from indoor PCB-containing window caulk and sealants in older buildings leading to inhalation exposure. PCB exposure, particularly to non-persistent, estrogenic congeners, may pose an unrecognized threat to female fecundity within the general population.

54 ENVIRONMENTAL SCIENCES↗

Structure and composition of blueberry fiber pectin and xyloglucan that bind anthocyanins during fruit puree processing

Blueberry is a well-known source of antioxidants and prebiotic dietary fiber yet the fate of these health-beneficial ingredients during fruit processing it is not understood. Detailed composition and structure of blueberry pomace (PF) remaining after commercial blueberry fruit puree processing, as well as the water soluble and water insoluble fractions, were determined. The PF was comprised of dietary fiber (60.8%) that was largely insoluble (46.2% vs. 14.6% soluble dietary fiber) pectin, xyloglucan, arabinoxylan and mannan polysaccharides, fructose (11.22%) and glucose (10.37%) free sugars, protein (9%), fat (5%), and anthocyanins (6444.5 μg/g). The most abundant anthocyanins detected in PF were malvidin 3-arabinoside and peonidin 3-glucoside and the pectin was determined to be methyl-esterified and acetylated rhamnogalacturonan I with a 4,5-unsaturated function at the non-reducing end based on oligosaccharide structural analysis. Blueberry PF xyloglucan oligosaccharide side chain structures included xylose, arabinose and galactose consistent with arabino-xyloglucan structure. Additionally, microwave-assisted extraction of blueberry PF (pH 2 for 10 min at 80 °C) was performed to more clearly elucidate pectin structure, and revealed a pectin polymer with high molar mass (1072 kDa) and viscosity that was dependent upon the molar mass. A random coil shape was confirmed for both the blueberry PF and microwave extracted blueberry pectin, which agreed with previous reports that flexible blueberry pectin contributes to strong anthocyanin binding. In summary, the blueberry pomace anthocyanin content was slightly higher than that reported for fresh whole blueberry fruit, which suggests that most blueberry anthocyanins adhered to the pomace fiber, and most likely the insoluble pectin, during and after processing.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Influence of site and soil properties on the DRIFT spectra of northern cold-region soils [Influence of site and soil properties on the mid-infrared spectra of northern cold-region soils]

Here, we investigated the influence of site characteristics and soil properties on the chemical composition of organic matter in soils collected from a latitudinal transect across Alaska through analysis of diffuse reflectance Fourier transform mid infrared (MidIR) spectra of bulk soils. The study included 119 soil samples collected from 28 sites including tundra, boreal forest, and grassland ecosystems. Organic, mineral, and cryoturbated soil horizons, both seasonally and perennially frozen, from a variety of depths and edaphic conditions were examined. The amount and chemical composition of organic matter as well as site and soil properties exerted a strong influence on the MidIR spectra. The spectra were highly sensitive to the extent of organic matter decomposition, enabling the ordination of Oi, Oe and Oa organic horizons. Differences in absorbance intensity for several spectral bands indicated that Oi horizons contained greater abundance of relatively fresh residues, phenolic-OH compounds, aliphatic compounds (waxes, lipids and fats), and carbohydrates. In contrast, Oa horizons had a greater presence of amide groups (possibly from microbial residues), aromatics, C=C bonds, carboxylates and carboxylic acids. Another significant factor differentiating these horizons was the incorporation of clays and silicates into the decomposing organic matter of Oa horizons. Calculated height peak ratios showed a clear trend to greater decomposition among Oi, Oe and Oa. The MidIR spectra were related to many site/soil attributes including land cover type, parent material, and associated factors, such as permafrost presence/absence, soil drainage, horizon depth, bulk density, cation exchange capacity, and pH. Single MidIR spectral bands were identified that might be used in future studies to quickly estimate the organic and inorganic carbon, total nitrogen, and carbon:nitrogen ratios of soils from northern latitudes. Lastly, our results demonstrate that the information contained in MidIR spectra of bulk soil integrates the quantity and chemical composition of soil organic matter with soil forming factors and highlights the potential for using this information to assess the degradation state of organic matter stored in northern cold-region soils.

58 GEOSCIENCES↗

Structural characterization of strawberry pomace

Strawberries are a nutrient dense food rich in vitamins, minerals, non-nutrient antioxidant phenolics, and fibers. Strawberry fiber bioactive structures are not well characterized and limited information is available about the interaction between strawberry fiber and phenolics. Therefore, we analyzed commercial strawberry pomace in order to provide a detailed carbohydrate structural characterization, and to associate structures with functions. The pomace fraction, which remained after strawberry commercial juice extraction, contained mostly insoluble (49.1 % vs. 5.6 % soluble dietary fiber) dietary fiber, with pectin, xyloglucan, xylan, β-glucan and glucomannan polysaccharides; glucose, fructose, xylose, arabinose, galactose, fucose and galacturonic acid free carbohydrates; protein (15.6 %), fat (8.34 %), and pelargonidin 3-glucoside (562 μg/g). Oligosaccharides from fucogalacto-xyloglucan, methyl-esterified rhamnogalacturonan I with branched arabinogalacto-side chains, rhamnogalacturonan II, homogalacturonan and β-glucan were detected by MALDI-TOF MS, NMR and glycosyl-linkage analysis. Previous reports suggest that these oligosaccharide and polysaccharide structures have prebiotic, bacterial pathogen anti-adhesion, and cholesterol-lowering activity, while anthocyanins are well-known antioxidants. A strawberry pomace microwave acid-extracted (10 min, 80 °C) fraction had high molar mass (2376 kDa) and viscosity (3.75 dL/g), with an extended rod shape. A random coil shape, that was reported previously to bind to phenolic compounds, was observed for other strawberry microwave-extracted fractions. These strawberry fiber structural details suggest that they can thicken foods, while the polysaccharide and polyphenol interaction indicates great potential as a multiple-function bioactive food ingredient important for gut and metabolic health.

59 BASIC BIOLOGICAL SCIENCES↗

Five-Year Analysis of Treatment Efficacy and Cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in Patients Treated With Accelerated Partial Breast Irradiation

Purpose: To present 5-year data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial. Methods and Materials: A total of 1440 patients (1449 cases) with early-stage breast cancer receiving breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial-breast irradiation (APBI) (34 Gy in 3.4-Gy fractions). Of 1449 cases, 1255 (87%) had invasive breast cancer (IBC) (median size, 10 mm) and 194 (13%) had ductal carcinoma in situ (DCIS) (median size, 8 mm). Median follow-up was 54 months. Results: Thirty-seven cases (2.6%) developed an ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial rate of 3.80% (3.86% for IBC and 3.39% for DCIS). Negative estrogen receptor status (p = 0.0011) was the only clinical, pathologic, or treatment-related variable associated with IBTR for patients with IBC and young age (<50 years; p = 0.0096) and positive margin status (p = 0.0126) in those with DCIS. The percentage of breasts with good/excellent cosmetic results at 60 months (n = 371) was 90.6%. Symptomatic breast seromas were reported in 13.0% of cases, and 2.3% developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 60.5 months, the 5-year actuarial rate of IBTR was 3.04%. Conclusion: Treatment efficacy, cosmesis, and toxicity 5 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Initial Clinical Experience With the Strut-Adjusted Volume Implant (SAVI) Breast Brachytherapy Device for Accelerated Partial-Breast Irradiation (APBI): First 100 Patients With More Than 1 Year of Follow-Up

Purpose: The Strut-Adjusted Volume Implant (SAVI; Cianna Medical, Aliso Viejo, CA) is a multichannel single-entry brachytherapy device designed to allow dose modulation to minimize normal tissue dose while simultaneously maximizing target coverage. This is the first report on the initial 102 patients with nearly 2 years of median follow-up. Methods and Materials: One hundred two patients were treated at two institutions. Data were collected on eligibility and dosimetry and followed for toxicity and recurrence. Results: The median follow-up is 21 months. Overall dosimetry is outstanding (median percent of target volume receiving 90% of the prescription dose was 95.9%, volume of target receiving 150% of the prescription dose was 27.8 mL, and volume of target receiving 200% of the prescription dose was 14.0 cm{sup 3}). No devices were pulled prior to treatment completion. For patients with a skin bridge of less than 7 mm, the maximum median skin dose was 280 cGy (median percent of target volume receiving 90% of the prescription dose was 95.2%, volume of target receiving 150% of the prescription dose was 25.8 cm{sup 3} and volume of target receiving 200% of the prescription dose was 12.7 mL). For patients with both chest wall and skin of less than 7 mm, the maximum median lung dose was 205 cGy with simultaneous skin dose of 272 cGy. The rate of telangiectasia was 1.9%. Grade 1 hyperpigmentation developed in 10 patients (9.8%) and Grade 2 fibrosis in 2 patients (1.9%). There were 2 symptomatic seromas and 2 cases of asymptomatic fat necrosis (1.9%). Of the patients, 27% were not eligible for MammoSite balloon brachytherapy (Hologic, Inc., Marlborough, MA) and 5% were not eligible for any balloon brachytherapy. The recurrence rate was 1%. Conclusions: The SAVI appears to safely allow an increase in eligibility for APBI over balloon brachytherapy or three-dimensional conformal radiation, highlighting the outstanding device flexibility to maximize the target dose and minimize the normal tissue dose. The device was well tolerated by patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Development of a Porcine Delayed Wound-Healing Model and Its Use in Testing a Novel Cell-Based Therapy

Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm{sup 2} wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of Macroscopic Pathology Measurements With Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases

Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r{sub s} = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r{sub s} = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r{sub s} = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r{sub s} = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Normal Tissue Anatomy for Oropharyngeal Cancer: Contouring Variability and Its Impact on Optimization

Purpose: To evaluate the variability of organ at risk (OAR) delineation and the resulting impact on intensity modulated radiation therapy (IMRT) treatment plan optimization in head-and-neck cancer. Methods and Materials: An expert panel of 3 radiation oncologists jointly delineated OARs, including the parotid and submandibular glands (SM), pharyngeal constrictors (PC), larynx, and glottis (GL), in 10 patients with advanced oropharynx cancer in 3 contouring sessions, spaced at least 1 week apart. Contour variability and uncertainty, as well as their dosimetric impact on IMRT planning for each case, were assessed. Results: The mean difference in total volume for each OAR was 1 cm{sup 3} ({sigma} 0.5 cm{sup 3}). Mean fractional overlap was 0.7 ({sigma} 0.1) and was highest (0.8) for the larynx and bilateral SMs and parotids and lowest (0.5) for PC. There were considerable spatial differences in contours, with the ipsilateral parotid and PC displaying the most variability (0.9 cm), which was most prominent in cases in which tumors obliterated fat planes. Both SMs and GL had the smallest differences (0.5 cm). The mean difference in OAR dose was 0.9 Gy (range 0.6-1.1 Gy, {sigma} 0.1 Gy), with the smallest difference for GL and largest for both SMs and the larynx. Conclusions: Despite substantial difference in OAR contours, optimization was barely affected, with a 0.9-Gy mean difference between optimizations, suggesting relative insensitivity of dose distributions for IMRT of oropharynx cancer to the extent of OARs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗