Metabolomics Approach in the Study of the Well-Defined Polyherbal Preparation Zyflamend

Eric D. Tague,Allen K. Bourdon,Amber MacDonald,Maggie S. Lookadoo,Edward D. Kim,Wesley M. White,Paul D. Terry,Shawn R. Campagna,Brynn H. Voy,Jay Whelan 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.3

Zyflamend is a highly controlled blend of 10 herbal extracts that synergistically impact multiple cell signaling pathways with anticancer and anti-inflammatory properties. More recently, its effects were shown to also modify cellular energetics, for example, activation of fatty acid oxidation and inhibition of lipogenesis. However, its general metabolic effects in vivo have yet to be explored. The objective of this study was to characterize the tissue specific metabolomes in response to supplementation of Zyflamend in mice, with a comparison of equivalent metabolomics data generated in plasma from humans supplemented with Zyflamend. Because Zyflamend has been shown to activate AMPK, the “energy sensor” of the cell, in vitro, the effects of Zyflamend on adiposity were also tested in the murine model. C57BL/6 mice were fed diets that mimicked the macro- and micronutrient composition of the U.S. diet with and without Zyflamend supplementation at human equivalent doses. Untargeted metabolomics was performed in liver, skeletal muscle, adipose, and plasma from mice consuming Zyflamend and in plasma from humans supplemented with Zyflamend at an equivalent dose. Adiposity in mice was significantly reduced in the Zyflamend-treated animals (compared with controls) without affecting body weight or weight gain. Based on KEGG pathway enrichment, purine and pyrimidine metabolism (potential regulators of AMPK) were particularly responsive to Zyflamend across all tissues, but only in mice. Consistent with the metabolomics data, Zyflamend activated AMPK and inhibited acetyl CoA-carboxylase in adipose tissue, key regulators of lipogenesis. Zyflamend reduces adipose tissue in mice through a mechanism that likely involves the activation of AMPK.

Lessons learnt in the management of primary invasive penile cancer in an Australian tertiary referral centre: Clinical outcomes with a minimum 48 months follow-up study

Eric Chung,Sun Yang,Louise White,Simon Wood,David Nicol 대한비뇨의학회 2015 Investigative and Clinical Urology Vol.56 No.2

Purpose: To report on lessons learnt in the management of primary invasive penile cancer in a major tertiary hospital in Australia. Materials and Methods: Medical records for all patients who underwent surgery for primary invasive penile cancer betweenJanuary 2000 and January 2011 were obtained. Patient demographics, clinical status of inguinal node, cancer stage and clinicaloutcomes were reviewed. All patients were followed up for a minimum of 48 months postoperative unless patient deceased withinthe first 48 months from the time of penile cancer surgery. Results: Over the 11-year period, a total of 23 cases of invasive penile cancer were identified. Partial penectomy was the mostcommon form of organ preserving surgery and the majority of patients have pT1b disease. Of the 9 patients with clinically palpableinguinal nodes, 7 patients were diagnosed with pN3 disease following inguinal lymphadenectomy. The Kaplan-Meier cancerspecificsurvival at 72 months showed decreasing survival based on tumour stage (83% in pT1, 79% in pT2, and 64% in pT3 disease)and nodal disease (100% in node negative, 50% in superficial inguinal lymphadenopathy, and 38% in patients with deep inguinaland/or pelvic lymphadenopathy) (p=0.082). The Kaplan-Meier cancer-specific survival revealed statistically significant difference insurvival outcome in patients with local recurrence vs. systemic metastasis disease (33% vs. 17%, p=0.008). Conclusions: The presence of high risk features such as tumour stage, lymph node involvement and distant metastasis carries asignificant higher risk of death and tumour recurrence in patients with penile cancer and inguinal lymph node metastasis.

형상기억합금이 적용된 플랩 시스템의 설계 및 해석

윤성호(Sungho Yoon),Scott R. White,Eric Loth 한국정밀공학회 2001 한국정밀공학회 학술발표대회 논문집 Vol.2001 No.10월

Aeroelastic Shock Boundary Layer Interaction

윤성호,김진영,Sridhar Krishnan,Scott R. White,Eric Loth 한국추진공학회 2001 한국추진공학회 학술대회논문집 Vol.2001 No.4

Gene Expression Profiling in Patients with Idiopathic Pulmonary Fibrosis (IPF) in the INMARK Trial

( Jin Woo Song ),( Moisés Selman ),( R Gisli Jenkins ),( Eric S White ),( Vincent Cottin ),( Yasuhiko Nishioka ),( Imre Noth ),( Antje Prasse ),( Benjamin Strobel ),( German Leparc ),( Carina Ittrich 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Background The INMARK trial investigated blood biomarkers as predictors of disease progression in patients with IPF and preserved lung function. In this study, we investigated changes in gene expression levels in patients treated with nintedanib and placebo. Methods Subjects with IPF and FVC ≥80% predicted were randomized 1:2 to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Total RNA was extracted from whole blood samples taken at baseline and week 12. Changes in gene expression levels from baseline to week 12 were analyzed. Data were log2 transformed prior to analysis. Changes in gene expression levels were considered significant if p≤0.05 and |log2fold change|≥0.5. Results Of 116 and 230 subjects randomized to receive nintedanib and placebo, respectively, data from 110 and 217 patients were included in the analysis. Of 60,675 genes evaluated, 14,799 had counts per million ≥1 in at least half the samples from either treatment group per time point and were included in the analysis. In adjusted analyses, compared with baseline levels, no genes were downregulated after 12 weeks’ treatment with placebo, while nine genes were downregulated after 12 weeks’ treatment with nintedanib (Table). No genes were upregulated. In unadjusted analyses, the change from baseline in expression level at week 12 was significantly different between nintedanib and placebo for five genes (SHISA4, LTF, CTSG, OLFM4, DEFA4) (Table). Pathways analysis suggested that the genes downregulated in patients treated with nintedanib were related to neutrophil function and extracellular matrix organization. Conclusions These analyses of the INMARK trial, based on genome-wide transcriptome profiling, identified a small number of genes that were downregulated after 12 weeks of nintedanib treatment in subjects with IPF and preserved lung function. The potential of gene expression profiling as a marker of treatment response in patients with IPF requires further study.

Measurement of Clavicle Fracture Shortening Using Computed Tomography and Chest Radiography

Reza Omid,Chris Kidd,Anthony Yi,Diego Villacis,Eric White 대한정형외과학회 2016 Clinics in Orthopedic Surgery Vol.8 No.4

Background: Nonoperative management of midshaft clavicle fractures has resulted in widely disparate outcomes and there is growing evidence that clavicle shortening poses the risk of unsatisfactory functional outcomes due to shoulder weakness and nonunion. Unfortunately, the literature does not clearly demonstrate the superiority of one particular method for measuring clavicle shortening. The purpose of this study was to compare the accuracy of clavicle shortening measurements based on plain radiographs with those based on computed tomography (CT) reconstructed images of the clavicle. Methods: A total of 51 patients with midshaft clavicle fractures who underwent both a chest CT scan and standardized anteroposterior chest radiography on the day of admission were included in this study. Both an orthopedic surgeon and a musculoskeletal radiologist measured clavicle shortening for all included patients. We then determined the accuracy and intraclass correlation coefficients for the imaging modalities. Bland-Altman plots were created to analyze agreement between the modalities and a paired t-test was used to determine any significant difference between measurements. Results: For injured clavicles, radiographic measurements significantly overestimated the clavicular length by a mean of 8.2 mm (standard deviation [SD], ± 10.2; confidence interval [CI], 95%) compared to CT-based measurements (p < 0.001). The intraclass correlation was 0.96 for both plain radiograph- and CT-based measurements (p = 0.17). Conclusions: We found that plain radiograph-based measurements of midshaft clavicle shortening are precise, but inaccurate. When clavicle shortening is considered in the decision to pursue operative management, we do not recommend the use of plain radiograph-based measurements.

Glenoid Bone Loss in Shoulder Instability: Superiority of Three-Dimensional Computed Tomography over Two-Dimensional Magnetic Resonance Imaging Using Established Methodology

Alexander E Weber,Ioanna K Bolia,Andrew Horn,Diego Villacis,Reza Omid,James E Tibone,Eric White,George F Hatch 대한정형외과학회 2021 Clinics in Orthopedic Surgery Vol.13 No.2

Background: Recent literature suggests that three-dimensional magnetic resonance imaging (3D MRI) can replace 3D computed tomography (3D CT) when evaluating glenoid bone loss in patients with shoulder instability. We aimed to examine if 2D MRI in conjunction with a validated predictive formula for assessment of glenoid height is equivalent to the gold standard 3D CT scans for patients with recurrent glenohumeral instability. Methods: Patients with recurrent shoulder instability and available imaging were retrospectively reviewed. Glenoid height on 3D CT and 2D MRI was measured by two blinded raters. Difference and equivalence testing were performed using a paired t -test and two one-sided tests, respectively. The interclass correlation coefficient (ICC) was used to test for interrater reliability, and percent agreement between the measurements of one reviewer was used to assess intrarater reliability. Results: Using an equivalence margin of 1 mm, 3D CT and 2D MRI were found to be different (p = 0.123). The mean glenoid height was significantly different when measured on 2D MRI (39.09 ± 2.93 mm) compared to 3D CT (38.71 ± 2.89 mm) (p = 0.032). The mean glenoid width was significantly different between 3D CT (30.13 ± 2.43 mm) and 2D MRI (27.45 ± 1.72 mm) (p < 0.001). The 3D CT measurements had better interrater agreement (ICC, 0.91) than 2D MRI measurements (ICC, 0.8). intrarater agreement was also higher on CT. Conclusions: Measurements of glenoid height using 3D CT and 2D MRI with subsequent calculation of the glenoid width using a validated methodology were not equivalent, and 3D CT was superior. Based on the validated methods for the measurement of glenoid bone loss on advanced imaging studies, 3D CT study must be preferred over 2D MRI in order to estimate the amount of glenoid bone loss in candidates for shoulder stabilization surgery and to assist in surgical decision-making.

Effects of Nintedanib on Markers of Epithelial Damage in Subjects with IPF: Data from the INMARK Trial

( Jin Woo Song ),( R Gisli Jenkins ),( Imre Noth ),( Moisés Selman ),( Vincent Cottin ),( Yasuhiko Nishioka ),( Antje Prasse ),( Eric S White ),( Carina Ittrich ),( Claudia Diefenbach ),( Klaus B Rohr 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Background The INMARK trial investigated effects of nintedanib on blood biomarkers in subjects with IPF. We investigated the effect of nintedanib on markers of epithelial damage. Methods Subjects (n=346) with IPF and FVC ≥80% predicted were randomised 1:2 to receive nintedanib 150 mg bid or placebo double-blind for 12 weeks, followed by open-label nintedanib for 40 weeks. Blood samples were taken at weeks 4, 8, 12, 16, 20, 24, 36, and 52. We assessed the rate of change (slope) in log10-transformed CA-125 and CA19-9 (two markers of epithelial damage) from baseline to week 12 using random coefficient regression and changes in log10-transformed CA-125 and CA19-9 over 52 weeks using a mixed model for repeated measures. Results The adjusted rate of change in CA-125 levels from baseline to week 12 was significantly different for nintedanib vs placebo (difference -0.046 U/mL/month [95% CI 0.056, -0.035]; p<0.001). Adjusted mean CA-125 levels decreased with nintedanib vs placebo from week 4; after week 12 CA-125 levels were similar between groups (Figure). There was no significant difference between nintedanib and placebo in the adjusted rate of change in CA19-9 levels from baseline to week 12 (difference -0.023 U/mL/month [95% CI -0.055, 0.009]; p=0.17). Adjusted mean CA19-9 levels over 52 weeks were similar in both groups. Conclusion CA-125 may be a biomarker of response to nintedanib in patients with IPF.