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Biomedical subjects

Eugene H Chung

Publications and source records attributed to Eugene H Chung.

5 recordsLinked to original sources

Clinical Profile and Mode of Initiation of Spontaneous Ventricular Tachyarrhythmias in Patients With Brugada Syndrome (START-BrS).

BACKGROUND: Data on the spontaneous onset of ventricular tachyarrhythmias (VTAs) in Brugada syndrome (BrS), including polymorphic ventricular tachycardia (PVT) and monomorphic ventricular tachycardia (MVT), remain limited. OBJECTIVES: The goal of this study was to compare the clinical profile and mode of initiation of PVT and MVT in BrS. METHODS: This retrospective multicenter registry included 154 patients with BrS from 29 centers with documented VTA initiation captured by implantable cardioverter-defibrillator (94.9%) or electrocardiogram (5.1%). A total of 234 VTAs were analyzed, and initiation patterns were classified by using predefined electrocardiographic criteria. RESULTS: PVT was observed in 80.5% of patients, MVT in 16.9%, and both in 2.6%. Patients with MVT tended to be older, exhibit drug-induced Brugada electrocardiogram, and were more frequently White. Pause-dependent initiation occurred in approximately 25% of PVT and approximately 33% of MVT episodes. Coupling intervals initiating PVT were nonsignificantly shorter than for MVT (median 368 milliseconds vs 395 milliseconds), with a significantly lower prematurity index and faster early arrhythmia cycle length. Antecedent premature ventricular complexes were present in approximately 43% of both VTA types, commonly sharing morphology with the initiating premature ventricular complex. The prevalence of pathogenic/likely pathogenic SCN5A mutation did not differ between groups. CONCLUSIONS: In this largest analysis to date of spontaneous VTA onset in BrS, MVT occurred in a substantial minority and was associated with older age, White ethnicity, drug-induced electrocardiogram pattern, and a preceding tachycardia. Initiation patterns were broadly similar across arrhythmia types, although PVT exhibited a significantly lower prematurity index and faster early cycle length despite only nonsignificant shorter coupling intervals. These findings refine the clinical and electrophysiological characterization of BrS-related arrhythmias and delineate distinct features of PVT and MVT initiation.

Adult↗

Biomimetic artificial ECMs stimulate bone regeneration.

We demonstrate that a biomimetic polymer network is capable of affecting bone regeneration in vivo. Starting with a foundation consisting of an environmentally responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel, we incorporated matrix metalloproteinase-13 (MMP-13) degradable crosslinkers and peptides containing integrin-binding domains (i.e., Arg-Gly-Asp) to create a biomimetic matrix designed to encourage osteoblast migration and proliferation. We independently tuned matrix stiffness and peptide concentration to generate a response surface model of osteoblast proliferation on different types of matrices. Osteoblast proliferation was significantly influenced by matrix stiffness (i.e., its complex modulus) and peptide concentration. When implanted in a rat femoral ablation model, these matrices induced bone regeneration only when protease degradable crosslinks were used to create the network. For the matrices with MMP-13 degradable crosslinkers, the bone formed had a trabecular-like structure and was distributed throughout the marrow space. Based on the correlated effects of matrix stiffness and ligand concentration, the response surface model will facilitate improvements in the regenerative capacity of these artificial extracellular matrices.

Animals↗

Hydrogels as artificial matrices for human embryonic stem cell self-renewal.

Human embryonic stem cells (hESCs) have the potential to differentiate into all cell types in the body and hold great promise for regenerative medicine; however, large-scale expansion of undifferentiated hESCs remains a major challenge. Self-renewal of hESCs requires culturing these cells on either mouse or human fibroblast cells (i.e., a feeder layer of cells), or on artificial extracellular matrices (ECMs) while supplementing the media with soluble growth factors. Here we report a completely synthetic ECM system composed of a semi-interpenetrating polymer network (sIPN), a polymer hydrogel, which was designed to allow the independent manipulation of cell adhesion ligand presentation and matrix stiffness. In the short term, hESCs that were cultured on the sIPN adhered to the surface, remained viable, maintained the morphology, and expressed the markers of undifferentiated hESCs. This was the first demonstration that a completely synthetic ECM can support short-term self-renewal of hESCs.

Biocompatible Materials↗

Synthetic MMP-13 degradable ECMs based on poly(N-isopropylacrylamide-co-acrylic acid) semi-interpenetrating polymer networks. I. Degradation and cell migration.

Thermoresponsive and injectable semi-interpenetrating polymer networks (sIPNs) containing a biospecific cell-adhesive signal and proteolytically degradable domains were developed as a synthetic equivalent of the extracellular matrix (ECM). The sIPNs synthesized define a modular hydrogel ECM where different properties of the matrix can be manipulated independently, thus creating a system where parametric analysis of the effect of hydrogel properties on cell proliferation and differentiation is possible. sIPNs composed of poly(N-isopropylacrylamide-co-acrylic acid) [p(NIPAAm-co-AAc)] and RGD-grafted poly(acrylic acid) linear chains [p(AAc)-g-RGD] were synthesized with peptide crosslinkers containing a matrix metalloproteinase-13 (MMP-13, collagenase-3) degradable domain. The lower critical solution temperature (LCST) of peptide-crosslinked p(NIPAAm-co-AAc) sIPNs was not influenced by the addition of either linear p(AAc) or peptide-modified p(AAc) chains ( approximately 34 degrees C) in PBS. Degradation of peptide-crosslinked hydrogels and sIPNs was enzyme specific and concentration dependent. Exposure of rat calvarial osteoblast (RCO) culture to the degradation products from the peptide-crosslinked hydrogels did not significantly affect cell viability. Migration of RCOs into the sIPNs was dependent upon the presence of both a cell-adhesive RGD peptide (Ac-CGGNGEPRGDTYRAY-NH2) and proteolytically-degradable crosslinks; however, there was greater dependence on the latter. The sIPNs synthesized are versatile materials for assessing cell fate in synthetic ECM constructs in vitro and tissue regeneration in vivo.

Acrylamides↗

Exercise testing in aortic stenosis.

Physician-supervised exercise testing in asymptomatic patients with aortic stenosis allows an objective assessment of the hemodynamic response to exercise and it provides a measure of exercise capacity. Exercise testing cannot be used to determine the presence or absence of coronary artery disease, but limited data indicate that exercise testing can provide prognostic information. The results of such testing can be used to provide an exercise prescription and to reassure the patient who might otherwise excessively limit his or her activity.

Aortic Valve Stenosis↗