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At least 1,027 records · Page 57
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

{sup 18}F-FDG-PET in Finnish patients with clinical suspicion of cardiac sarcoidosis: Female sex and history of atrioventricular block increase the prevalence of positive PET findings

Introduction: Fluorodeoxyglucose positron emission tomography (FDG-PET) is a non-invasive imaging modality that has been shown to be a feasible method to demonstrate myocardial inflammation. The aim of this study was to identify the patients suspected of having cardiac sarcoidosis (CS), who are most likely to benefit from PET imaging. Materials and methods: 137 patients suspected of having CS underwent a dedicated cardiac FDG-PET examination at Tampere University Hospital between August 2012 and September 2015. These examinations were retrospectively analyzed. Results: 33 and 12 of the 137 patients had abnormal left and right ventricular (LV and RV) FDG-uptake, respectively. Abnormal LV-uptake and RV-uptake were significantly associated with female sex and a history of advanced AV-block (P < 0.05). Abnormal RV-uptake was also associated with ventricular tachycardia and atrial fibrillation (P < 0.05). 56% of the 27 female patients with a history of AV-block had a pathological PET finding compared to only 6% of the 49 male patients without a history of AV-block. There were 17 female patients with history of both AV-block and ventricular tachycardia, 71% of them had abnormal PET finding. Conclusions: Abnormal FDG-PET findings were associated with female sex, AV-block, and arrhythmias in this clinical cohort.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Relationship of non-invasive quantification of myocardial blood flow to arrhythmic events in patients with implantable cardiac defibrillators

Background: Ischemia contributes to arrhythmogenesis though its role is incompletely understood. Abnormal myocardial perfusion measured by PET imaging may predict ventricular arrhythmias (VAs) in a high-risk population. Methods: Patients with implantable cardiac defibrillators who had undergone rubidium-82 cardiac PET imaging were identified. Patients were stratified by median MBF and MFR values for analysis. The Cox proportional hazards model was used to assess the impact of myocardial perfusion on survival free of VT independent of critical covariates. Results: A total of 159 patients (124 (78%) males, median age 65.9 years, IQR [56.76-72.63]) were followed for 1.43 years IQR [0.83-2.21]. VA occurred in 29 patients (23.7%). After adjustment for ejection fraction, age, and sex, impaired stress MBF was associated with an increased risk of VA (adjusted HR per ml/min/g 1.52, 95% CI (1.01-2.31), P = 0.04). Summed rest and stress scores were not predictive of VA. Among patients with severe LV dysfunction, stress MBF remained an independent predictor of VA (adjusted HR per 1 ml/min/g HR 1.69, 95% CI (1.03-11.36), P = 0.03), while residual EF, summed rest, and summed stress scores were not (P > 0.05). Conclusions: Impaired stress myocardial blood flow was associated with less survival free of ventricular arrhythmias.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT

Background: SPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). Methods: Fifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of {sup 99m}Tc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. Results: Overall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image analysis also produced a similar accuracy, sensitivity, and specificity. CFR was normal in 6, each with CAD on SCA with an overall accuracy of 91%, sensitivity of 80%, and specificity of 100%. The mean CFR was significantly lower for SCA detected abnormal than for normal patients (3.86±1.06 vs 1.94±0. 0.67, P < 0.001). Conclusions: The visually assessed image findings in static and dynamic SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion based on SCA. The CFR measured with dynamic SPECT is fully objective, with better sensitivity and specificity, available only with the data generated from the dynamic SPECT method.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Coronary calcium score influences referral for invasive coronary angiography after normal myocardial perfusion SPECT

Background: In patients with normal SPECT but persistent complaints, invasive angiography may exclude obstructive coronary disease. We assessed whether high coronary artery calcium (CAC) scores are associated with increased referral for invasive angiography following normal SPECT. Methods and results: 2286 consecutive patients (mean age 60 ± 12, 39% male) with normal SPECT were assessed. All patients underwent simultaneous CAC scoring. Patients were categorized into four groups based on their CAC score: CAC = 0 (n = 694), CAC 1 to 100 (n = 891), CAC 101 to 400 (n = 368), and CAC >400 (n = 333). The decision to perform angiography was left to the discretion of treating physician. Follow-up angiography was confined to the first 60 days after SPECT. Occurrence of MACE (late revascularization, myocardial infarction or death) was recorded. Overall, 100 patients (4.4%) underwent early angiography with increasing rates in higher CAC score groups (1.0%, 2.6%, 8.4%, and 11.7%), respectively, P < .001). A CAC score >400 (OR 3.56, 95% CI 2.19 to 5.77, P < .001) was independently associated with referral to angiography. Similarly, CAC score >400 was an independent predictor for MACE (HR 9.26, 95% CI 5.06 to 16.93). Early angiography did not influence prognosis (HR 1.57, 95% CI 0.91 to 2.73). Conclusions: CAC scoring impacts clinical decision-making and increases referral rates for invasive angiography after normal SPECT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Prediction of long-term (> 10 year) cardiovascular outcomes in heart transplant recipients: Value of stress technetium-99m tetrofosmin myocardial perfusion imaging

Background: Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is useful in the evaluation of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) recipients. The current study evaluated the long-term prognostic value of stress SPECT MPI for predicting all-cause mortality and cardiac events in HTx recipients. Methods: The study population consisted of 166 HTx recipients (mean age 54 ± 10 years, 84% male) who underwent exercise or dobutamine stress {sup 99m}Tc-tetrofosmin SPECT MPI for the assessment of CAV. An abnormal SPECT MPI was defined as the presence of a fixed or a reversible perfusion defect. Endpoints were all-cause mortality, cardiac mortality, and non-fatal myocardial infarction (MI). Results: MPI abnormalities were detected in 55 patients (33%), including fixed defects in 28 patients (17%), partially reversible in 17 patients (10%), and completely reversible defects in 10 patients (6%). During a median follow-up of 12.8 years (range 0-15, mean follow-up 9.5 years), 109 (66%) patients died (all-cause mortality), of which 67 (40%) were due to cardiac causes. A total of 5 (3%) patients experienced a non-fatal MI. HTx recipients with a normal stress {sup 99m}Tc-tetrofosmin SPECT MPI had a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the initial test. The presence of a reversible perfusion defect was a significant predictor of all-cause mortality, cardiac mortality, and major cardiac events, during the entire follow-up period. Conclusions: Stress {sup 99m}Tc-tetrofosmin SPECT MPI provides valuable prognostic information for the prediction of long-term outcome in HTx recipients. Patients with a normal stress {sup 99m}Tc-tetrofosmin SPECT MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after initial testing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Additional value of systolic wall thickening in myocardial stunning evaluated by stress-rest gated perfusion SPECT

Aim and patients: The aim of the present study is to evaluate the additional value of systolic wall thickening to myocardial perfusion in diagnosing myocardial stunning in patients with angiography proven coronary artery disease. We selected 91 ischemic patients (82 males; mean age 59.7 ± 10.3) with CAD documented by angiography. Ischemia was defined as a summed difference score ≥5. All patients underwent a 2-day gated perfusion SPECT protocol. The patients received a dose of 740 MBq of {sup 99m}Tc-tetrofosmin after stress and at rest. Treadmill maximal exercise tests were performed on all patients. Results: The post-stress LVEF was significantly lower than rest LVEF (48.1% ± 10.3% vs 50.3% ± 10.7%; P = .0001). The wall thickening summed difference score was 4.44 ± 4.13 (P = .0001). At a multivariate regression analysis, only WT-SDS as independent variable was significantly correlated with myocardial ischemia (SDS). We also divided patients according to SDS in those with mild (SDS < 8) and severe (SDS ≥ 8) ischemia. WT-SDS, but not ∆LVEF, was significantly different between groups. Conclusions: WT-SDS, more than the depression in the global function (∆LVEF) of the left ventricle, correlates with the degree of ischemia and better identifies, when present, the stunning phenomenon.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

{sup 18}F-FDG PET/CT-imaging of left ventricular assist device infection: a retrospective quantitative intrapatient analysis

Background: Despite the use of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT), diagnosis of a driveline infection in ventricular assist device (LVAD) recipients remains challenging. Our aim was to evaluate the potential of a baseline {sup 18}F-FDG PET/CT (prior to an infection) for the diagnosis of an LVAD-related infection. Methods: We retrospectively selected all LVAD recipients who had undergone two consecutive whole-body {sup 18}F-FDG PET/CT examinations between January 2010 and December 2016. PET/CT was analyzed qualitatively (uptake pattern) and semi-quantitatively (SUV{sub max} and ∆SUV{sub max}). SUV{sub max} was measured and compared in five distinctive volumes of interest along the LVAD driveline. An SUV{sub max} threshold was calculated. Final diagnosis was made by clinical examination, microbiological parameters, and molecular imaging. Results: Thirty patients were enrolled (mean age 54 ± 12 years; 26 male). Mean difference in SUV{sub max} for all five positions between the first and the second PET/CT along the driveline was significantly higher in patients with an LVAD-related infection (mean ∆SUV{sub max} = 4.38 ± 1.44) compared to those without a driveline infection (mean ∆SUV{sub max} = 0.03 ± 0.43), P < 0.05. Applying ROC analysis, an SUV{sub max} threshold of 3.88 resulted in a sensitivity and specificity of 100%, respectively. There were three distinctive uptake patterns in patients with a driveline infection. Conclusion: PET/CT diagnosis in the context of an LVAD-related infection can be improved by comparison to a baseline examination using a distinctive SUV{sub max} threshold.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Non-cardiac uptake of technetium-99m pyrophosphate in transthyretin cardiac amyloidosis

Background: Technetium-based bone scintigraphy is rapidly becoming the most common non-invasive imaging tool in the diagnosis of Transthyretin cardiac amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m-pyrophosphate (TcPYP) in patients with ATTR. Methods and Results: This was a retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a semiquantitative scale (grades 0 to 3) and on single-photon emission computed tomography (SPECT) with CT attenuation correction using total myocardial counts per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps), vertebral body, LV myocardium, and blood pool mean counts were calculated. In the cohort (age 78 ± 9 years, 77% male, and 30% hereditary ATTR), there was no visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT assessment. Total and blood pool-corrected uptake in the muscle groups were significantly less than myocardium and bone (P < 0.001). Blood pool-corrected muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps P = 0.69). As bony uptake decreased, there was no corresponding increase in skeletal muscle uptake. Conclusions: In patients with ATTR cardiac amyloidosis, skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and quantitative metrics, and is not significantly different in patients with grade 2 vs 3 semiquantitative uptake. The properties of this tracer may be different than TcDPD with respect to non-cardiac uptake.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Reliability of the {sup 123}I-mIBG heart/mediastinum ratio: Results of a multicenter test–retest reproducibility study

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of {sup 123}I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test–retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test–retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m{sup 2}. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test–retest difference was 0.055 to 0.076. Bland–Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to {sup 123}I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of {sup 123}I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Arterial inflammation in young patients with human immunodeficiency virus infection: A cross-sectional study using F-18 FDG PET/CT

Background: HIV infection is associated with the risk of development of atherosclerosis at a younger age. We compared arterial inflammation in HIV-infected and HIV-uninfected patients with otherwise low-risk factors for cardiovascular disease (CVD) using FDG PET/CT. Methods: 242 patients aged 18–40 years with low-risk factors for CVD consisting of 121 HIV-infected patients and 121 HIV-uninfected age- and gender-matched controls were studied, mean age = 34.95 ± 5.46 years. We calculated and compared the target-to-background ratio of FDG uptake in ascending aorta of HIV-infected and non-infected patients. Results: Median CD4 count and viral load were 375.5 cells/mm{sup 3} (range 2-1094) and 6391.00 copies/mL (range 24-1,348,622), respectively. There was slightly higher but significant overlap in the TBR between HIV-infected group compared with control (1.22, 0.87-2.02 vs. 1.12, 0.38-1.40, P < 0.001). TBR was neither affected by CD4 count levels nor the presence or absence of detectable viremia. We also found no significant difference in TBR between male and female patients with HIV infection. We found a weak positive correlation between TBR and CD4 count, TBR and duration of HIV infection, and a very weak negative correlation between TBR and viral load. There was no significant difference in TBR between patients on HAART and those not yet commenced on therapy. Conclusion: Marginally higher TBR with a significant overlap exist in HIV-infected patients compared with control. Arterial F-18 FDG uptake is not affected by the CD 4 count, viral load, gender, or duration of HIV infection.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Improved diagnostic accuracy of thallium-201 myocardial perfusion single-photon emission computed tomography with CT attenuation correction

Background: The benefits of attenuation correction (AC) in technetium-99m myocardial perfusion imaging (MPI) have been well established. However, the value of thallium (Tl-201) AC and routine computed tomography AC (CTAC) were less well established. The aims of this study were to evaluate the diagnostic performance of thallium (Tl-201) MPI with additional CTAC and to determine which participants would benefit most. Methods and Results: A total of 108 consecutive patients who underwent Tl-201 MPI and received coronary angiography within 3 months were enrolled. Diagnostic performance was determined by sensitivity, specificity, and receiver operating characteristic curve analysis. Subgroup analyses were performed using gender and obesity. CTAC improved the area under the curve (0.84 vs. 0.77, P = 0.037 at patient level), primarily due to a significant improvement in specificity (0.78 vs. 0.57, P = 0.013) and no significant difference in sensitivity (0.79 vs. 0.82, P = 0.75). In subgroup analysis, CTAC was most helpful in obese subjects, men, and especially right coronary artery lesions. Conclusions: CTAC significantly improved diagnostic performance primarily by increasing the specificity, and the improvements were significantly greater in obese patients and male patients. These findings suggest that CTAC should be applied to Tl-201 MPI as routine clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Comorbid conditions in individuals assessed by SPECT: Study of a reference cardiology center in Mexico City

Background: There is an increasing prevalence of comorbidities in patients with ischemic heart disease (IHD) in developing countries. The aim of this work is to assess the prevalence of comorbidities and associated factors for IHD among patients at a reference cardiology center. Design and Methods: This was a cross-sectional study. A complete clinical history which focused on the main comorbidities, previous myocardial infarction, and the main reason of referral was assessed. A single-photon emission computed tomography (SPECT) myocardial perfusion study (MPS) with two protocols was performed. Results: We included 1998 patients, 64.2% male, median age 63 (I.R.: 56–71) years. 1514 (75.8%) subjects had at least one associated comorbidity. The main comorbidity was diabetes (T2D) (772: 38.6%), followed by systemic hypertension (737: 36.9%), smoking (518: 25.9%), and dyslipidemia (517: 25.9%). 806 (40.3%) had histories of previous myocardial infarctions. The main cause of referral was angina (923: 46.2%). We identified 1330 (66.5%) abnormal MPS. 460 (23%) had ischemia, 292 (14.6%) infarction, and 578 (28.9%) ischemia and infarction. Conclusion: An increased prevalence of comorbidities was found in patients who were studied in the Nuclear Cardiology Department (NCD): most of them had traditional risk factors attributable to myocardial infarction. A great percentage were newly diagnosed with both ischemia and infarction.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Large-scale additive manufacturing tooling for extrusion-compression molds

Carbon fiber reinforced polymer composites (CFPC) have been used in additive manufacturing (AM) due to both the high-strength-to-weight and superior-stiffness-to-weight ratios. CF AM is being considered for tooling applications. In AM, CFPCs are usually aligned along the deposition direction; however, it results in anisotropic thermal properties which affect the heat transfer and warpage of the final part. In this study, three male molds with different infill patterns were produced via the material extrusion additive manufacturing (EDF-AM) process. These include (a) 0°: infill pattern along the printing direction; (b) 90°: infill pattern perpendicular to the printing direction; and (c) 0°/90°: alternate layers along and perpendicular directions. The effect of the infill pattern on thermal conductivity was analyzed and observed that 0° infill (surface temperature: 79.2°C) had the highest conductivity; and 90° infill (surface temperature: 66.4°C) had the least.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Supplemental dietary full-fatted and defatted Desmodesmus sp. exerted similar effects on growth performance, gut health, and excreta hydrothermal liquefaction of broiler chicks

This study determined effects of full-fatted (C046, 41% crude protein) and lipid extracted (LEA, 39% crude protein) microalgae Desmodesmus sp. on growth performance, gut health, and excreta hydrothermal liquefaction of broiler chickens. Two experiments were conducted by feeding day-old Cornish male chicks: 1) a corn-soybean meal basal diet (control) 2) control +5% C046, or 3) control +5% LEA for 2 weeks. Growth performance was measured weekly in both experiments. Blood, liver, and duodenum samples of chickens were collected for biochemical analyses, and excreta samples were collected for hydrothermal liquefaction (300 °C, 60 min) at the end of Experiment 2. Compared with the control, supplemental dietary C046 and LEA enhanced average daily gain (13% to 40%, p < 0.05) in both experiments, and improved feed efficiency (15% and 11%, p < 0.01) in Experiment 2. The C046 and LEA diets enhanced the duodenum (19% to –2 fold, p < 0.05), but decreased the liver (17 to 78%, p < 0.05) mRNA abundances of interleukins-1, 6 and 8 and (or) tumor necrosis factor-α, respectively, compared with the controls. Meanwhile, the two types of biomass enhanced the protein amounts of claudin-1 in the duodenum (5–34%, p < 0.05) than the controls. Hydrothermal liquefaction of the excreta derived from the three diets showed no major differences in total bio-crude oil (average of 23%), hydrochar yield (average of 12%), or elemental compositions. However, the heating values of the resultant two bio-crude oils from the microalgae-fed chicken excreta (average of 34 MJ/kg) were 16% greater than those from the control chickens (29 MJ/kg). In conclusion, supplementing the full- and de-fatted Desmodesmus sp. microalgal biomass in the starter diets for broiler chickens produced largely similar improvements of growth performance, gut health, and excreta-derived oil quality.

09 BIOMASS FUELS↗
DOE OSTI2022

Excessive Aurantiochytrium acetophilum docosahexaenoic acid supplementation decreases growth performance and breast muscle mass of broiler chickens

We report Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid with health-promoting potential. This study was to investigate effects of supplemental DHA from Aurantiochytrium acetophilum on growth performance, health status, meat quality, and protein synthesis signaling of broiler chickens. Day-old male chicks were housed in an environmental control room (6 cages/treatment, 8 chicks/cage), and fed a corn-soybean meal basal diet supplemented with the DHA-rich A. acetophilum biomass (Heliae, Gilbert, AZ) at 0, 1, 2, and 4% (0, 1.7, 3.4 and 6.8 g DHA/kg diet) for 6 weeks. Growth performance was measured weekly. Blood samples were collected at weeks 3 and 6 (2 chicks/cage). Four tissues were sampled (2 chicks/cage) for biochemical and meat quality analyses. Data were analyzed by one-way ANOVA and regression. Compared with the control, the 4% A. acetophilum diet decreased (p < 0.05) body weight gain (19%) and gain to feed ratio (19%) during weeks 4–6. The A. acetophilum supplementation dose-dependently decreased (p < 0.05, R 2 = 0.21–0.54) plasma alanine amino transferase activity and glucose concentrations, but had little effect on plasma activity of alkaline phosphatase or concentrations of inorganic phosphorus and uric acid at weeks 3 and 6. Compared with the control, the 4% A. acetophilum diet decreased (p < 0.05) breast muscle weight by 21%, and down-regulated (p < 0.05) mRNA levels of mammalian target of rapamycin and ribosomal s6 protein (S6), and protein levels of phosphorylated S6 to S6 and phosphorylated S6 kinase beta 1 to S6 kinase beta 1. The A. acetophilum supplementation linearly increased (p < 0.01) lipid peroxidation (R 2 = 0.62–0.90) and hardness and chewiness (R 2 = 0.34–0.44) of breast and thigh muscles. In conclusion, supplemental 4% (6.8 g DHA/kg), but not 1 or 2%, of A. acetophilum impaired growth performance, breast muscle mass accumulation, and(or) protein synthesis signaling of broilers.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Impacts of feeding three strains of microalgae alone or in combination on growth performance, protein metabolism, and meat quality of broiler chickens

Variations in nutrient compositions, especially amino acid (AA) profiles, among microalgal species may enable a superior feeding outcome from a combined than singular supplementation in poultry diets. Therefore, a feeding trial was conducted to compare the effects of three strains of microalgal biomass supplemented alone or in combination to replace 5 % (starter) and 10 % (grower) soybean meal (on weight-to-weight basis) on growth performance, protein metabolism, and meat quality of broiler chickens. Day-old Cornish Cross male chicks (total = 180) were divided into 5 groups (6 cages/treatment, 6 birds/cage) and fed a corn-soybean meal basal diet (BD), BD + H117 (Chlorella sp., H117), BD + C985 (Tetraselmis sp., C985), BD + Nannochloropsis oceanica (NO), and BD + H117 + C985 + NO (Combination). Feeding any of the microalgae diets did not alter growth performance nor meat quality including texture, pH, color, and water holding capacity of breast and thigh meats. However, the breast weight percentages were decreased (P < 0.05) by feeding the C985, NO, and Combination diets. Compared with the BD, the 4 microalgal diets led to higher (P < 0.05) plasma uric acid and protein concentrations at weeks 3 and (or) 6. The mRNA levels of MAFbx, MURF1, FOXO1, and calpastatin in the breast and thigh muscles were altered by the microalgal diets but not those of genes associated with other quality traits. In conclusion, replacing 5 % or 10 % soybean meal with three sources of microalgae in broiler diets decreased breast weights percentage but not absolute weight. Furthermore, feeding chickens with the combination of three microalgae did not restore the breast loss and induced different expressions of genes related to muscle hypertrophy or atrophy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Epigenetic effects of paternal cocaine on reward stimulus behavior and accumbens gene expression in mice

Paternal cocaine use causes phenotypic alterations in offspring behavior and associated neural processing. In rodents, changes in first generation (F1) offspring include drug reward behavior, circadian timing, and anxiety responses. This study, utilizing a murine (C57BL/6J) oral cocaine model, examines the effects of paternal cocaine exposure on fundamental characteristics of offspring reward responses, including: 1) the extent of cocaine-induced effects after different durations of sire drug withdrawal; 2) sex- and drug-dependent differences in F1 reward preference; 3) effects on second generation (F2) cocaine preference; and 4) corresponding changes in reward area (nucleus accumbens) mRNA expression. We demonstrate that paternal cocaine intake over a single ˜40-day spermatogenic cycle significantly decreased cocaine (but not ethanol or sucrose) preference in a sex-specific manner in F1 mice from sires mated 24h after drug withdrawal. However, F1 offspring of sires bred 4 months after withdrawal did not exhibit altered cocaine preference. Altered cocaine preference also was not observed in F2's. RNASeq analyses of F1 accumbens tissue revealed changes in gene expression in male offspring of cocaine-exposed sires, including many genes not previously linked to cocaine addiction. Enrichment analyses highlight genes linked to CNS development, synaptic signaling, extracellular matrix, and immune function. Expression correlation analyses identified a novel target, Fam19a4, that may negatively regulate many genes in the accumbens, including genes already identified in addiction. Collectively, these results reveal that paternal cocaine effects in F1 offspring may involve temporally limited epigenetic germline effects and identify new genetic targets for addiction research.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Poly(ADP-ribosylation) regulates chromatin organization through histone H3 modification and DNA methylation of the first cell cycle of mouse embryos

Highlights: •Histone modification of the mouse pronuclei is regulated by poly(ADP-ribosylation). •Hypermethylation of the mouse female pronuclei is maintained by poly(ADP-ribosylation). •Parp1 is physically interacted with Suz12, which may function in the pronuclei. •Poly(ADP-ribosylation) affects ultrastructure of chromatin of the mouse pronucleus. -- Abstract: We examined the roles of poly(ADP-ribosylation) in chromatin remodeling during the first cell cycle of mouse embryos. Drug-based inhibition of poly(ADP-ribosylation) by a PARP inhibitor, PJ-34, revealed up-regulation of dimethylation of histone H3 at lysine 4 in male pronuclei and down-regulation of dimethylation of histone H3 at lysine 9 (H3K9) and lysine 27 (H3K27). Association of poly(ADP-ribosylation) with histone modification was suggested to be supported by the interaction of Suz12, a histone methyltransferase in the polycomb complex, with Parp1. PARP activity was suggested to be required for a proper localization and maintenance of Suz12 on chromosomes. Notably, DNA methylation level of female pronuclei in one-cell embryos was robustly decreased by PJ-34. Electron microscopic analysis showed a frequent appearance of unusual electron-dense areas within the female pronuclei, implying the disorganized and hypercondensed chromatin ultrastructure. These results show that poly(ADP-ribosylation) is important for the integrity of non-equivalent epigenetic dynamics of pronuclei during the first cell cycle of mouse embryos.

60 APPLIED LIFE SCIENCES↗