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Article ; Online: Multiaxial pulsatile dynamics of the thoracic aorta and impact of thoracic endovascular repair

Ga-Young Suh / Johan Bondesson / Yufei D. Zhu / Jason T. Lee / Michael D. Dake / Christopher P. Cheng

European Journal of Radiology Open, Vol 8, Iss , Pp 100333- (2021)

2021

Abstract: Purpose: The thoracic aorta is a highly mobile organ whose dynamics are altered by thoracic endovascular aorta repair (TEVAR). The aim of this study was to quantify cardiac pulsatility-induced multi-axial deformation of the thoracic aorta before and ... ...

Abstract	Purpose: The thoracic aorta is a highly mobile organ whose dynamics are altered by thoracic endovascular aorta repair (TEVAR). The aim of this study was to quantify cardiac pulsatility-induced multi-axial deformation of the thoracic aorta before and after descending aortic TEVAR. Methods: Eleven TEVAR patients (8 males and 3 females, age 57–89) underwent retrospective cardiac-gated CT angiography before and after TEVAR. 3D geometric models of the thoracic aorta were constructed, and lumen centerlines, inner and outer surface curves, and cross-sections were extracted to measure aortic arclength, centerline, inner surface, and outer surface longitudinal curvatures, as well as cross-sectional effective diameter and eccentricity for the ascending and stented aortic portions. Results: From pre- to post-TEVAR, arclength deformation was increased at the ascending aorta from 5.9 ± 3.1 % to 8.8 ± 4.4 % (P < 0.05), and decreased at the stented aorta from 7.5 ± 5.1 % to 2.7 ± 2.5 % (P < 0.05). Longitudinal curvature and diametric deformations were reduced at the stented aorta. Centerline curvature, inner surface curvature, and cross-sectional eccentricity deformations were increased at the distal ascending aorta. Conclusions: Deformations were reduced in the stented thoracic aorta after TEVAR, but increased in the ascending aorta near the aortic arch, possibly as a compensatory mechanism to maintain overall thoracic compliance in the presence of reduced deformation in the stiffened stented aorta.
Keywords	TEVAR ; Thoracic aorta ; Deformation ; Cardiac pulsatility ; Aortic dissection ; Aortic aneurysm ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	516
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of the Use of Phosphatidic Acid in the Diet on Growth Performance and Breast Meat Yield in Broilers

Eric B. Sobotik / Jason T. Lee / Scott Hagerman / Gregory S. Archer

Animals, Vol 8, Iss 6, p

2018 Volume 87

Abstract: The use of feed additives to improve feed conversion while increasing growth is the goal of any broiler nutrition program. Therefore, it is important to evaluate potential feed additives not only for increased performance, but also for any negative ... ...

Abstract	The use of feed additives to improve feed conversion while increasing growth is the goal of any broiler nutrition program. Therefore, it is important to evaluate potential feed additives not only for increased performance, but also for any negative attributes. A study was conducted to evaluate the effects of feeding phosphatidic acid (PA) to broiler chickens. Two experiments were conducted using exercise in conjunction with PA (Experiment 1(E1)) and administering PA at different inclusion rates in the diet (Experiment 2 (E2)); LowPA (5 mg/bird/day), MidPA (10 mg/bird/day), HighPA (15 mg/bird/day), and control (CON). All birds were weighed bi-weekly during the experiments to obtain average pen weights and feed conversion ratios (FCRs). At the end of the experiments, eight birds per pen were processed to evaluate carcass traits and breast yield. In E1, exercise did not affect growth, feed conversion or processing traits (p > 0.05). However, PA supplementation did increase growth, carcass and breast weight, and carcass and breast yields (p < 0.05). In E2, differences (p < 0.05) in live bird weights between the control birds (1.65 kg) and all PA treatments (pooled mean: 1.73 kg) began at 28 days; however, only the LowPA carried that effect (p = 0.05) through to the conclusion of the trial (3.55 vs. 3.81 kg). Overall, LowPA (1.64) and MidPA (1.69) had lower (p < 0.05) FCRs than the CON treatment (1.74). Increased growth observed in live bird weights in the LowPA translated to increased (p < 0.05) overall carcass weights (2.78 vs. 2.99 kg) and specifically breast filet weights (0.69 vs. 0.76 kg). Yields did not differ (p > 0.05), but with the increased weight feeding LowPA resulted in more total breast meat. Phosphatidic acid did not affect (p > 0.05) woody breast or white striping. In conclusion, dietary PA improved FCR, increased live bird weights, and increased breast fillet weight without increased incidence of white striping. These results indicate that feeding PA may increase production efficiency in broilers.
Keywords	broiler ; phosphatidic acid ; growth ; yield ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Subject code	630 ; 590
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in murine dilated cardiomyopathy

Al-Hassan J. Dajani / Michael B. Liu / Michael A. Olaopa / Lucian Cao / Carla Valenzuela-Ripoll / Timothy J. Davis / Megan D. Poston / Elizabeth H. Smith / Jaime Contreras / Marissa Pennino / Christopher M. Waldmann / Donald B. Hoover / Jason T. Lee / Patrick Y. Jay / Ali Javaheri / Roger Slavik / Zhilin Qu / Olujimi A. Ajijola

JCI Insight, Vol 8, Iss

2023 Volume 22

Abstract: Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We ... ...

Abstract	Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve fibers versus controls. Further, the severity of transmural innervation gradients was correlated with VAs. Transmural innervation gradients were also identified in human left ventricular free wall samples from DCM versus controls. We investigated mechanisms underlying this relationship by in silico studies in 1D, 2D, and 3D models of failing and normal human hearts, finding that arrhythmogenesis increased as heterogeneity in sympathetic innervation worsened. Specifically, both DCM-induced myocyte electrical remodeling and spatially inhomogeneous innervation gradients synergistically worsened arrhythmogenesis. Thus, heterogeneous innervation gradients in DCM promoted arrhythmogenesis. Restoration of homogeneous sympathetic innervation in the failing heart may reduce VAs.
Keywords	Cardiology ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of miRNA signatures associated with radiation-induced late lung injury in mice.

Claude J Rogers / Agnes I Lukaszewicz / Jason Yamada-Hanff / Ewa D Micewicz / Josephine A Ratikan / Mark A Starbird / Thomas A Miller / Christine Nguyen / Jason T Lee / Tove Olafsen / Keisuke S Iwamoto / William H McBride / Dörthe Schaue / Naresh Menon

PLoS ONE, Vol 15, Iss 5, p e

2020 Volume 0232411

Abstract: Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non- ... ...

Abstract	Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 2528 Variable utilization of cross-sectional imaging prior to percutaneous peripheral vascular interventions

Nathan K. Itoga / Kenneth Tran / Vivian Ho / Venita Chandra / Ronald L. Dalman / Edmund J. Harris / Jason T. Lee / Matthew W. Mell

Journal of Clinical and Translational Science, Vol 2, Pp 90-

2018 Volume 90

Abstract: OBJECTIVES/SPECIFIC AIMS: Reducing radiologic exams has been a focus of cost reduction in healthcare systems. The utility and justification of obtaining cross-sectional imaging (PPCSI) before surgical intervention continues to be evaluated. For ... ...

Abstract	OBJECTIVES/SPECIFIC AIMS: Reducing radiologic exams has been a focus of cost reduction in healthcare systems. The utility and justification of obtaining cross-sectional imaging (PPCSI) before surgical intervention continues to be evaluated. For peripheral artery disease (PAD) consensus guidelines regarding PPCSI do not exist and may be influenced by patient complexity, variation of disease presentation, and physician preference. The objective of this study was to determine the utility of PPCSI before percutaneous PAD intervention. METHODS/STUDY POPULATION: Patients receiving first-time endovascular revascularization procedure for PAD from 2013 to 2015 were evaluated for PPCSI done within 180 days prior to revascularization. Patient and physician demographics, perioperative characteristics, and disease distribution/severity were evaluated. The primary outcome was technical success defined as improving inflow and/or revascularization of the target outflow vessels to <50% stenosis. RESULTS/ANTICIPATED RESULTS: Of the 348 patients who underwent an attempted revascularization procedure 159 (45.7%) patients underwent PPCSI, including 151 CTA and 8 MRA. Of these, 48% were ordered by the referring provider (84% at an outside institution), and 52% were ordered by the treating physician. PPCSI was performed a median of 26 days (IQR 9-53) prior to procedure. Individual vascular surgeon practice identified PPCSI rates ranging from 31% to 70%. On multivariate analysis chronic kidney disease (OR=0.35; CI 0.17–0.73) had the strongest effect against of PPCSI, and Inpatient/ED evaluation (OR=3.20; CI 1.58–6.50), aorto-iliac (OR=2.78; CI 1.46–5.29) and femoral-popliteal occlusions (OR=2.51; CI 1.38–4.55) most strongly predicted PPCSI. After excluding 31 diagnostic procedures, technical success did not differ between endovascular procedures with PPSCI (91.3%) or without PPCSI (85.6%), p=0.11. When analyzing 89 femoral-popliteal occlusions, technical success was higher with PPCSI (88%) compared to procedures without PPSCI (69%), ...
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Performing radiosynthesis in microvolumes to maximize molar activity of tracers for positron emission tomography

Maxim Sergeev / Mark Lazari / Federica Morgia / Jeffrey Collins / Muhammad Rashed Javed / Olga Sergeeva / Jason Jones / Michael E. Phelps / Jason T. Lee / Pei Yuin Keng / R. Michael van Dam

Communications Chemistry, Vol 1, Iss 1, Pp 1-

2018 Volume 10

Abstract: For many applications, positron emission tomography tracers must be produced with high specific activity. Here the authors identify variables leading to increased specific activity when tracers are synthesized in microliter volumes, and show that ... ...

Abstract	For many applications, positron emission tomography tracers must be produced with high specific activity. Here the authors identify variables leading to increased specific activity when tracers are synthesized in microliter volumes, and show that specific activity can influence tracer biodistribution.
Keywords	Chemistry ; QD1-999
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers

Shili Xu / Arthur Catapang / Daniel Braas / Linsey Stiles / Hanna M. Doh / Jason T. Lee / Thomas G. Graeber / Robert Damoiseaux / Orian Shirihai / Harvey R. Herschman

Cancer & Metabolism, Vol 6, Iss 1, Pp 1-

2018 Volume 17

Abstract: Abstract Background Precision medicine therapies require identification of unique molecular cancer characteristics. Hexokinase (HK) activity has been proposed as a therapeutic target; however, different hexokinase isoforms have not been well ... ...

Abstract	Abstract Background Precision medicine therapies require identification of unique molecular cancer characteristics. Hexokinase (HK) activity has been proposed as a therapeutic target; however, different hexokinase isoforms have not been well characterized as alternative targets. While HK2 is highly expressed in the majority of cancers, cancer subtypes with differential HK1 and HK2 expression have not been characterized for their sensitivities to HK2 silencing. Methods HK1 and HK2 expression in the Cancer Cell Line Encyclopedia dataset was analyzed. A doxycycline-inducible shRNA silencing system was used to examine the effect of HK2 knockdown in cultured cells and in xenograft models of HK1−HK2+ and HK1+HK2+ cancers. Glucose consumption and lactate production rates were measured to monitor HK activity in cell culture, and 18F-FDG PET/CT was used to monitor HK activity in xenograft tumors. A high-throughput screen was performed to search for synthetically lethal compounds in combination with HK2 inhibition in HK1−HK2+ liver cancer cells, and a combination therapy for liver cancers with this phenotype was developed. A metabolomic analysis was performed to examine changes in cellular energy levels and key metabolites in HK1−HK2+ cells treated with this combination therapy. The CRISPR Cas9 method was used to establish isogenic HK1+HK2+ and HK1−HK2+ cell lines to evaluate HK1−HK2+ cancer cell sensitivity to the combination therapy. Results Most tumors express both HK1 and HK2, and subsets of cancers from a wide variety of tissues of origin express only HK2. Unlike HK1+HK2+ cancers, HK1−HK2+ cancers are sensitive to HK2 silencing-induced cytostasis. Synthetic lethality was achieved in HK1−HK2+ liver cancer cells, by the combination of DPI, a mitochondrial complex I inhibitor, and HK2 inhibition, in HK1−HK2+ liver cancer cells. Perhexiline, a fatty acid oxidation inhibitor, further sensitizes HK1−HK2+ liver cancer cells to the complex I/HK2-targeted therapeutic combination. Although HK1+HK2+ lung cancer H460 cells are ...
Keywords	Precision medicine ; Warburg effect ; Liver cancer ; Cancer ; Glycolysis ; Hexokinase 2 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	610
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeted Inhibition of EGFR and Glutaminase Induces Metabolic Crisis in EGFR Mutant Lung Cancer

Milica Momcilovic / Sean T. Bailey / Jason T. Lee / Michael C. Fishbein / Clara Magyar / Daniel Braas / Thomas Graeber / Nicholas J. Jackson / Johannes Czernin / Ethan Emberley / Matthew Gross / Julie Janes / Andy Mackinnon / Alison Pan / Mirna Rodriguez / Melissa Works / Winter Zhang / Francesco Parlati / Susan Demo /

Edward Garon / Kostyantyn Krysan / Tonya C. Walser / Steven M. Dubinett / Saman Sadeghi / Heather R. Christofk / David B. Shackelford

Cell Reports, Vol 18, Iss 3, Pp 601-

2017 Volume 610

Abstract: Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on ... ...

Abstract	Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death, resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18F-fluoro-2-deoxyglucose (18F-FDG) and 11C-glutamine (11C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following treatment with CB-839 + erlotinib. Therefore, PET imaging with 18F-FDG and 11C-Gln tracers can be used to non-invasively measure metabolic response to CB-839 and erlotinib combination therapy.
Keywords	EGFR ; lung cancer ; glutamine ; erlotinib ; CB-839 ; PET imaging ; AMPK ; metabolic crisis ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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