Amir Lerman

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (605)4698.79 Total impact

  • Circulation Cardiovascular Imaging 12/2015; 8(1). DOI:10.1161/CIRCIMAGING.114.002636 · 5.32 Impact Factor
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    ABSTRACT: Purpose: Perirenal fat is associated with poor blood pressure control and chronic kidney disease, but the underlying mechanisms remain elusive. We tested the hypothesis that perirenal fat impairs renal arterial endothelial function in pigs with obesity-metabolic derangements (ObM). Material and methods: Fourteen domestic pigs were studied after 16 weeks of a high-fat/high-fructose diet (ObM) or standard chow (Lean). Renal blood flow (RBF), glomerular filtration rate (GFR), and visceral fat volumes were studied in-vivo with CT. Renal arterial endothelial function was also studied ex-vivo in the organ bath. Results: ObM pigs demonstrated increased body weight, blood pressure, cholesterol, and intra-abdominal fat compared to lean pigs, and perirenal fat volume was significantly larger. RBF and GFR were markedly elevated, while urinary protein level was preserved. Ex-vivo acetylcholine-induced endothelium-dependent vasodilation of renal artery rings was substantially impaired in ObM compared to Lean. Endothelial function was further blunted in both ObM and Lean arterial rings by incubation with perirenal fat harvested from ObM, but not from Lean pigs, and was restored by inhibition of tumor necrosis factor (TNF)-α. ObM perirenal fat also showed increased pro-inflammatory macrophage infiltration and TNF-α expression. Conclusions: ObM perirenal fat directly causes renal artery endothelial dysfunction, partly mediated by TNF-α.
    The Journal of urology 09/2015; DOI:10.1016/j.juro.2015.08.105 · 4.47 Impact Factor
  • Amir Lerman · Taek-Geun Kwon · Lilach O Lerman
    JACC. Cardiovascular imaging 09/2015; 8(9):1068-70. DOI:10.1016/j.jcmg.2015.05.008 · 7.19 Impact Factor
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    ABSTRACT: Epicardial adipose tissue (EAT) has been recognized as a sensitive marker of cardiometabolic risk. Recent evidence suggests efficacy of long-term statin therapy in reducing EAT in patients with coronary artery disease. Whether short-term statin therapy is associated with changes in the volume of EAT is currently unknown. A cohort of patients with atrial fibrillation who underwent pulmonary vein isolation were randomized to receive either 80 mg/day of atorvastatin (n = 38, 32 men, age 56 ± 11 years) or placebo (n = 41, 33 men, age 56 ± 10 years) for a 3-month period. EAT volume was assessed by cardiac computed tomography at baseline and at follow-up. Patients randomized to statin treatment exhibited a modest but significant decrease in median EAT volume (baseline vs follow-up: 92.3 cm(3) [62.0 to 133.3] vs 86.9 cm(3) [64.1 to 124.8], p <0.05), whereas median EAT remained unchanged in the placebo group (81.9 cm(3) [55.5 to 110.9] vs 81.3 cm(3) [57.1 to 110.5], p = NS). Changes in median systemic inflammatory markers and lipid profile were also seen with statin treatment: C-reactive protein (2.4 mg/L [0.7 to 3.7] vs 1.1 mg/L [0.5 to 2.7], p <0.05), total cholesterol (186 mg/dL [162.5 to 201] vs 123 mg/dL [99 to 162.5], p <0.001), and low-density lipoprotein cholesterol (116 mg/dL [96.5 to 132.5] vs 56 [40.5 to 81] mg/dL, p <0.001) diminished, whereas median body mass index did not change (27.8 kg/m(2) [25 to 30] versus 27.6 kg/m(2) [25.7 to 30.5], p = NS). No variations occurred in the placebo group. In conclusion, short-term intensive statin therapy significantly reduced the volume of EAT in patients with atrial fibrillation.
    The American journal of cardiology 09/2015; DOI:10.1016/j.amjcard.2015.07.067 · 3.28 Impact Factor
  • Jaskanwal D Sara · Lilach O Lerman · Amir Lerman
    Journal of the American College of Cardiology 09/2015; 66(10):1116-8. DOI:10.1016/j.jacc.2015.07.030 · 16.50 Impact Factor
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    ABSTRACT: Current risk models for predicting long-term mortality after percutaneous coronary intervention are restricted to all-cause mortality. We sought to develop novel risk models for the prediction of cardiac and noncardiac mortality after percutaneous coronary intervention. We retrospectively evaluated patients who underwent index percutaneous coronary intervention at Mayo Clinic from 2003 to 2008. Long-term deaths were ascertained through scheduled prospective surveillance. Cause of death was determined via telephone interviews, medical records, and autopsy reports. Fine and Gray extension of Cox proportional hazards models was used to model cause-specific cumulative incidence. Candidate variables and interactions were chosen a priori, without variable selection methods. Resulting models were mapped to an integer-based risk score. The study comprised 6636 patients followed up over a median of 62 months (25th, 75th percentiles: 45, 77 months). There were 1488 deaths, 518 (35%) cardiac, 938 (63%) noncardiac, and 32 (2%) unknown. The 5-year predicted cardiac mortality ranged from 0.6% to 97%, with a corrected c-statistic of 0.82. Risk factors for cardiac death included age, body mass index, ejection fraction, and history of congestive heart failure. The integer score for noncardiac death included age, medicine index, body mass index, current smoker, noncardiac Charlson index and cardiac Charlson index, and accommodated significant age-based interactions for smoking and the 2 Charlson indices. Predicted noncardiac mortality at 5 years ranged from 0.2% to 81%, with a corrected c-statistic of 0.77. We report novel risk models to predict cardiac and noncardiac long-term mortality after percutaneous coronary intervention. © 2015 American Heart Association, Inc.
    Circulation Cardiovascular Interventions 09/2015; 8(9). DOI:10.1161/CIRCINTERVENTIONS.114.002121 · 6.22 Impact Factor
  • Soumen Jana · Amir Lerman · Robert D Simari
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    ABSTRACT: The fibrosa layer of a cardiac aortic valve is composed mostly of a dense network of type I collagen fibers oriented in circumferential direction. This main layer bears the tensile load and responds to the high stress on a leaflet. The inner fibrosa layer is also the site of pathophysiologic changes that result in valvular dysfunction, including stenosis and regurgitation. In vitro studies of these changes are limited by the absence of a substrate that mimics the circumferentially oriented structure of the fibrosa layer. In heart valve tissue engineering, generation of this layer is challenging. This study aimed to develop an artificial fibrosa layer of a native aortic leaflet. A unique morphologically biomimicked, pliable but standalone substrate with circumferentially oriented nanofibers was fabricated by electrospinning on a novel collector designed for this study. The substrate had low-bulk tensile stiffness and ultimate strength; thus, cultured valvular interstitial cells (VICs) showed a fibroblast phenotype that is generally observed in healthy aortic leaflet. Furthermore, gene and protein expression and morphology of VICs in substrates were close to those in the fibrosa layer of a native aortic leaflet. This artificial fibrosa layer can be useful for in vitro studies of valvular dysfunctions.
    ACS Applied Materials & Interfaces 08/2015; 7(36). DOI:10.1021/acsami.5b04805 · 6.72 Impact Factor
  • Soumen Jana · Amir Lerman
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    ABSTRACT: Heart valve tissue engineering could be a possible solution for the limitations of mechanical and biological prostheses, which are commonly used for heart valve replacement. In tissue engineering, cells and their aggregates are seeded into a 3-dimensional platform, termed the scaffold, to make the engineered tissue construct. However, mimicking the mechanical and spatial heterogeneity of a heart valve structure in a fabricated scaffold with uniform cell distribution is daunting when approached conventionally. Bioprinting is an emerging technique that can produce biological products containing matrix and cells, together or separately with morphological, structural and mechanical diversity. This advance increases the possibility of fabricating the structure of a heart valve in vitro and using it as a functional tissue construct for implantation. This review describes the use of bioprinting technology in heart valve tissue engineering. Copyright © 2015. Published by Elsevier Inc.
    Biotechnology advances 08/2015; DOI:10.1016/j.biotechadv.2015.07.006 · 9.02 Impact Factor
  • Mayo Clinic Proceedings 08/2015; 90(8):1167-8. DOI:10.1016/j.mayocp.2015.05.013 · 6.26 Impact Factor
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    ABSTRACT: Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients. We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7 %) vs. suboptimal (HbA1c ≥ 7 %) glycaemic control at the time of catheterization. Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6 %, p = 0.40) and dependent CMD (61.7 vs. 62.2 %, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95 % 1.04-1.18; p < 0.001) and female gender (OR 3.87; CI 95 % 1.45-11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95 % 0.95-0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95 % 0.23-1.46; p 0.26) or dependent CMD (OR 0.99, CI 95 % 0.43-2.24; p = 0.98). The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed.
    Cardiovascular Diabetology 08/2015; 14(1):106. DOI:10.1186/s12933-015-0269-1 · 4.02 Impact Factor
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    ABSTRACT: Background: Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. Methods and results: In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial-dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ CBF Ach) and diameter (% Δ CAD Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3<TSH≤10.0 mU/mL, n=1200. Subjects with a history of hypothyroidism had a significantly lower % Δ CBF Ach (48.26 [80.66] versus 64.58 [128.30]) compared to patients with euthyroidism, while the % Δ CAD Ach did not vary significantly between groups. After adjusting for covariates, females with hypothyroidism still had a significantly lower % Δ CBF Ach (estimated difference in % Δ CBF Ach [SE]: -16.79 [8.18]). Conclusions: Hypothyroidism in women is associated with microvascular endothelial dysfunction, even after adjusting for confounders, and may explain some of the increased risk of cardiovascular disease in these patients.
    Journal of the American Heart Association 07/2015; 4(8). DOI:10.1161/JAHA.115.002225 · 4.31 Impact Factor
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    ABSTRACT: Myocardial perfusion scintigraphy (MPS) is used widely to assess cardiovascular risk in patients with chest pain. The utility of carotid intima-media thickness (CIMT) and endothelial function as assessed by reactive hyperemia-peripheral arterial tonometry index (RHI) in risk stratifying patients with angina-like symptoms needs to be defined. We investigated whether the addition of CIMT and RHI to Framingham Cardiovascular Risk Score (FCVRS) and MPS improves comprehensive cardiovascular risk prediction in patients presenting with angina-like symptoms. We enrolled 343 consecutive patients with angina-like symptoms suspected of having stable angina. MPS, CIMT, and RHI were performed and patients were followed for cardiovascular events for a median of 5.3years (range 4.4-6.2). Patients were stratified by FCVRS and MPS. During the follow-up, 57 patients (16.6%) had cardiovascular events. Among patients without perfusion defect, low RHI was significantly associated with cardiovascular events in the intermediate and high FCVRS groups (hazard ratio (HR) [95% confidence interval (CI)] of RHI≤2.11 was 6.99 [1.34-128] in the intermediate FCVRS group and 6.08 [1.08-114] in the high FCVRS group). Furthermore, although MPS did not predict, only RHI predicted hard cardiovascular events (cardiovascular death, myocardial infarction, and stroke) independent from FCVRS, and adding RHI to FCVRS improved net reclassification index (20.9%, 95% CI 0.8-41.1, p=0.04). Especially, RHI was significantly associated with hard cardiovascular events in the high FCVRS group (HR [95% CI] of RHI≤1.93 was 5.66 [1.54-36.4], p=0.007). Peripheral endothelial function may improve discrimination in identifying at-risk patients for future cardiovascular events when added to FCVRS-MPS-based risk stratification. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 07/2015; 190(1). DOI:10.1016/j.ijcard.2015.04.124 · 4.04 Impact Factor
  • Taek-Geun Kwon · Lilach O Lerman · Amir Lerman
    Journal of the American College of Cardiology 06/2015; 65(23):2478-2480. DOI:10.1016/j.jacc.2015.04.032 · 16.50 Impact Factor
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    ABSTRACT: Obesity and hypertension are major risk factors for cardiovascular diseases, and their growing coexistence accounts for an increase in adverse cardiac events, but the mechanisms are yet to be determined. We hypothesized that obesity exacerbates mitochondrial dysregulation imposed by hypertension and augments left ventricular dysfunction. Obesity-prone Ossabaw pigs were randomized to lean (standard diet) and obese (high-fat diet), without (Lean-sham and Obese-sham) or with renovascular hypertension (Lean-hypertension and Obese-hypertension), induced after 12 weeks of diet (n=7 each). Cardiac function, myocardial perfusion and oxygenation, and microvascular remodeling were assessed 4 weeks later. Mitochondrial biogenesis signals and structural proteins, respiratory chain complex activities, and mitochondrial self-degradation were examined, as was fibrosis. Obesity alone exerted no apparent effect on mitochondrial dynamics, but aggravated in hypertensive hearts the reduction of mitochondrial proteins, deoxyribonucleic acid content, and respiratory chain complex IV subunits activity, and amplified mitochondrial self-degradation. Synergistic interaction of obesity with hypertension also exacerbated myocardial fibrosis and left ventricular diastolic dysfunction. Mitochondrial content, respiratory chain complex IV subunits activity, and mitophagy were correlated with myocardial fibrosis. These findings suggest that obesity aggravates in renovascular hypertension cardiac mitochondrial aberrations. Mitochondrial function may regulate the progression of cardiac injury and functional deterioration in hypertension concomitant with obesity. © 2015 American Heart Association, Inc.
    Hypertension 06/2015; 66(2). DOI:10.1161/HYPERTENSIONAHA.115.05478 · 6.48 Impact Factor
  • Feilong Wang · Amir Lerman · Joerg Herrmann
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    ABSTRACT: The ubiquitin-proteasome system (UPS) is an integral part of the protein metabolism and protein quality control in eukaryotic cells. It is involved in a number of biological processes of significance for vascular biology and pathology such as oxidative stress, inflammation, foam cell formation, and apoptosis. This review summarizes both indirect and direct lines of evidence for a role of the UPS in atherosclerosis from the initiation to the progression and complication stage and concludes with a future perspective.
    American Journal of Cardiovascular Disease 06/2015; 5(1):83-100.
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    ABSTRACT: Cardiac rehabilitation (CR) following myocardial infarction is vastly underused. As such, the aim of this study was to test a digital health intervention (DHI) as an adjunct to CR. Patients undergoing standard Mayo Clinic CR were recruited prior to CR (n = 25) or after 3 months CR (n = 17). Changes in risk factors and rehospitalizations plus emergency department (ED) visits were assessed after 3 months. Patients assigned to DHI during CR had significant reductions in weight (-4.0 ± 5.2 kg, P = .001), blood pressure (-10.8 ± 13.5 mmHg, P = .0009), and the group using DHI after 3 months of CR had significant reductions in weight (-2.5 ± 3.8 kg, P = .04) and systolic BP (-12.6 ± 12.4 mmHg, P = .001) compared to the control groups. Both DHI groups also displayed significant reductions in rehospitalizations/ED visits (-37.9 %, P = 0.01 and -28 %, P = .04, respectively). This study suggests that a guideline-driven DHI CR program can augment secondary prevention strategies during usual CR by improving risk factors for repeat events.
    Journal of Cardiovascular Translational Research 05/2015; 8(5). DOI:10.1007/s12265-015-9629-1 · 3.02 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    JACC. Cardiovascular Interventions 05/2015; 8(6):824-33. DOI:10.1016/j.jcin.2015.01.029 · 7.35 Impact Factor
  • JACC. Cardiovascular Interventions 05/2015; 8(6):834-6. DOI:10.1016/j.jcin.2014.12.245 · 7.35 Impact Factor
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    R. Jay Widmer · Jocelyn M. Widmer · Amir Lerman
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    ABSTRACT: We currently face a myriad of grand global challenges in fields such as poverty, the environment, education, science, and medicine. However, our current means of dealing with such challenges has fallen short, and ingenious solutions are required to overcome the inherent resistance to progress toward ameliorating such difficulties. Here, we highlight the promises and challenges of international collaboration in achieving success toward these trials. We note prior successes in fields such as education, medicine, science, and environmental issues made to date, yet at the same time we do note deficiencies and shortcomings in these efforts. Hence, the notion of international collaboration should be strengthened and encouraged by governments, non-profit organizations, and others moving forward using creative means to bring talented teams together to tackle these challenges across the globe.
    04/2015; 6(2):e0012. DOI:10.5041/RMMJ.10196
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    ABSTRACT: Left ventricular (LV) hypertrophy (LVH) plays an important role in hypertensive heart disease, and may be accompanied by myocardial autophagy. However, the pattern of autophagy during evolution of LVH is unclear. We hypothesized that autophagy activation indicates advancing cardiac LVH with tissue remodeling. Ten domestic pigs with a 10-week unilateral renovascular hypertension (HTN) were classified as mild or moderate HTN (n = 5 each group) based on the degree of renal artery stenosis (above or below 75%). Seven normal pigs served as controls. Left ventricular remodeling, function, and microvascular density were assessed using multi-detector- and micro-computed tomography and histology. Markers of myocardial autophagic and endoplasmic reticulum (ER) stress-related unfolded protein response (UPR), apoptosis, and fibrosis were examined ex vivo. Both HTN groups had increased myocyte cross-sectional area, but it was greater in moderate HTN, accompanied by elevated LV muscle-mass. Moderate, but not mild HTN, also showed impaired microvascular density and impaired myocardial perfusion. Autophagy mediators were unaltered in mild HTN but UPR markers were increased, while in moderate HTN they were all upregulated, whereas UPR markers were suppressed. Myocardial apoptosis and fibrosis were also greater in moderate HTN. Autophagic proteins were correlated with LVH and fibrosis. Autophagic activity is stimulated during the exacerbation of LVH, following a transient early increase in ER stress, and may be involved in the progression of cardiac remodeling in renovascular hypertensive heart disease. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email:
    American Journal of Hypertension 04/2015; DOI:10.1093/ajh/hpv057 · 2.85 Impact Factor

Publication Stats

23k Citations
4,698.79 Total Impact Points


  • 2013–2015
    • Sun Yat-Sen University
      • Department of Vascular Surgery
      Shengcheng, Guangdong, China
  • 1999–2015
    • Mayo Foundation for Medical Education and Research
      • • Division of Cardiovascular Diseases
      • • Department of Internal Medicine
      Рочестер, Michigan, United States
  • 1990–2015
    • Mayo Clinic - Rochester
      • • Department of Cardiovascular Diseases
      • • Department of Internal Medicine
      Рочестер, Minnesota, United States
  • 2006–2013
    • Konyang University Hospital
      Gaigeturi, Jeju-do, South Korea
  • 2012
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 2004–2012
    • Rochester College
      Rochester, New York, United States
  • 2011
    • University of Florida
      Gainesville, Florida, United States
  • 2002–2009
    • University of Minnesota Rochester
      Rochester, Minnesota, United States
    • University Hospital Essen
      Essen, North Rhine-Westphalia, Germany
  • 2008
    • Vanderbilt University
      Нашвилл, Michigan, United States
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 2003
    • Technion - Israel Institute of Technology
      H̱efa, Haifa District, Israel
    • Second University of Naples
      Caserta, Campania, Italy
    • Aarhus University
      Aarhus, Central Jutland, Denmark
  • 2000
    • University of Pennsylvania
      • Department of Pediatrics
      Filadelfia, Pennsylvania, United States
  • 1998
    • University of Zurich
      Zürich, Zurich, Switzerland
    • University of Rome Tor Vergata
      Roma, Latium, Italy