387 research outputs found

    Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers

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    Background/AimsOccult HBV infection can persist following HBsAg loss and be transmitted, but the virological features are not well defined.MethodsHere we investigated 25 Korean patients who lost HBsAg during follow up, either spontaneously or subsequent to therapy.ResultsWhereas subtype adr (genotype C) was found in 96% of HBsAg positive patients, 75 % of patients who lost HBsAg spontaneously were seemed to be infected with the ayw subtype with sequence similar to genotype D. Mutations in the major hydrophilic region (MHR) of HBsAg were found in 7 patients who lost HBsAg spontaneously. The mutations include T123S, M125I/N, C139R, D144E, V177A, L192F, and W196L, some of which have not been reported before. Functional analysis via transfection experiments indicate that the C139R and D144E mutations drastically reduced HBsAg antigenicity, while the Y225del mutation found in one interferon-treated patient impaired HBsAg secretion.ConclusionsLack of detectable HBsAg in patient serum could be explained by low level of ccc DNA in liver tissue, low antigenicity of the surface protein, or its secretion defect

    Detection of Single Nanoparticles inside a Single Terahertz Resonator

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    With the rapid advancement of 5G/6G communications using millimeter wavelengths, the concomitant usage of these long wavelength radiation for remote sensing and monitoring of biological and chemical agents is anticipated. However, the ability to detect and identify these agents with sizes ranging from nanometers to microns is hampered by its millimeter wavelength, which drastically reduces the interaction cross-section. Herein, it is reported that single gold nanoparticles (NPs) drop-casted on the nanoresonator can be observed by monitoring the far-field transmitting spectra of individual terahertz (THz) nanoresonators, which enhance the electric field hundreds of times on the nanoscale. Despite the enormous mismatch in length scales, full-wave 3D numerical modeling of the single THz nanoresonator is also performed to interpret the experimental results, indicating the possibility to turn off the resonance using only one NP embedded in the hotspot of the nanoresonator. Such NP detection becomes the most sensitive when the particle, whose size is comparable to the gap width, is tightly fitted into the nanoresonator. This work unveils the potential associated with refractive index sensing and hyperspectral absorption spectroscopy for detecting and fingerprinting ultra-low density of bio/chemical molecules such as viruses, lipid vesicles, and explosives

    Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries

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    Background: This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameterduring ergonovine provocation testing.Methods: A total of 158 patients who underwent an ergonovine provocation test with intracoronaryadenosine injection between 2011 and 2014 were selected. Patients were divided into four groups basedon the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1,induced spasm < 50%; Group 2, 50–89%; Group 3, 90–99%; and Group 4, total occlusion.Results: Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ±± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardialartery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3,and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4,respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lowerin patients with spasm positive results (0.68 [0.59–0.76] vs. 0.18 [0.00–0.41], p < 0.001 in the studypopulation; 0.60 [0.54–0.67] vs. 0.40 [0.27–0.44], p < 0.001 in Group 2) with the best cut-off value of0.505 (sensitivity 0.955, specificity 0.921).Conclusions: Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstrictedepicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter wassignificantly lower in patients with spasm positive results

    Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.

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    BackgroundDiabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.PurposeWe hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.MethodsRat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.ResultsQuantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.ConclusionTwo isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP

    Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide-naïve chronic hepatitis B patients in Korea: data from the clinical practice setting in a single-center cohort

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    Background/AimsThis study assessed the antiviral efficacy and safety of tenofovir disoproxil fumarate (TDF) for up to 12 months in Korean treatment-naïve chronic hepatitis B (CHB) patients.MethodsA total of 411 treatment-naïve CHB patients who had been treated with TDF for at least 3 months (median 5.6) were consecutively enrolled. Clinical, biochemical, virological parameters and treatment adherence were routinely assessed every 3 months.ResultsThe median age was 51.3 years, 63.0% of the patients were male, 49.6% were HBeAg (+), and 210 patients had liver cirrhosis. The median baseline HBV DNA was 5.98 (SD 1.68) log10 IU/mL. Among the patients completing week 48, 83.3% had a complete virologic response (CVR, <12 IU/mL by HBV PCR assay), and 88.2% had normalized levels of alanine aminotransferase (ALT). The cumulative probabilities of CVR at 3, 6, 9 and 12 months were 22.8%, 53.1%, 69.3% and 85.0%. During the follow-up period, 9.8% patients achieved HBeAg loss and 7.8% patients achieved HBeAg seroconversion. There was no virological breakthrough after initiating TDF. The most common TDF-related adverse event was gastrointestinal upset, and three patients discontinued TDF therapy. However, no serious life-threatening side effect was noted.ConclusionsIn a clinical practice setting, TDF was safe and highly effective when administered for 12 months to Korean treatment-naïve CHB patients

    Performance evaluation of the HepB Typer-Entecavir kit for detection of entecavir resistance mutations in chronic hepatitis B

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    Background/AimsMolecular diagnostic methods have enabled the rapid diagnosis of drug-resistant mutations in hepatitis B virus (HBV) and have reduced both unnecessary therapeutic interventions and medical costs. In this study we evaluated the analytical and clinical performances of the HepB Typer-Entecavir kit (GeneMatrix, Korea) in detecting entecavir-resistance-associated mutations.MethodsThe HepB Typer-Entecavir kit was evaluated for its limit of detection, interference, cross-reactivity, and precision using HBV reference standards made by diluting high-titer viral stocks in HBV-negative human serum. The performance of the HepB Typer-Entecavir kit for detecting mutations related to entecavir resistance was compared with direct sequencing for 396 clinical samples from 108 patients.ResultsUsing the reference standards, the detection limit of the HepB Typer-Entecavir kit was found to be as low as 500 copies/mL. No cross-reactivity was observed, and elevated levels of various interfering substances did not adversely affect its analytical performance. The precision test conducted by repetitive analysis of 2,400 replicates with reference standards at various concentrations showed 99.9% agreement (2398/2400). The overall concordance rate between the HepB Typer-Entecavir kit and direct sequencing assays in 396 clinical samples was 99.5%.ConclusionsThe HepB Typer-Entecavir kit showed high reliability and precision, and comparable sensitivity and specificity for detecting mutant virus populations in reference and clinical samples in comparison with direct sequencing. Therefore, this assay would be clinically useful in the diagnosis of entecavir-resistance-associated mutations in chronic hepatitis B

    Prospective Validation of FibroTest in Comparison with Liver Stiffness for Predicting Liver Fibrosis in Asian Subjects with Chronic Hepatitis B

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    Liver stiffness measurement (LSM) and FibroTest (FT) are frequently used as non-invasive alternatives for fibrosis staging to liver biopsy. However, to date, diagnostic performances of Enhanced Liver Fibrosis (ELF) test, which consists of hyaluronic acid, aminoterminal propeptide of procollagen type-III, and tissue inhibitor of matrix metalloproteinases-1, have not been compared to those of LSM and FT in Asian chronic hepatitis B (CHB) patients.Between June 2010 and November 2011, we prospectively enrolled 170 CHB patients who underwent liver biopsies along with LSM, FT, and ELF. The Batts system was used to assess fibrosis stages.Areas under receiver operating characteristic curves (AUROCs) to predict significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4) were 0.901, 0.860, and 0.862 for ELF, respectively; 0.937, 0.956, and 0.963 for LSM; and 0.896, 0.921, and 0.881 for FT. AUROCs to predict F≥2 were similar between each other, whereas LSM and FT had better AUROCs than ELF for predicting F≥3 (both p<0.05), and LSM predicted F4 more accurately than ELF (p<0.05). Optimized cutoffs of ELF to maximize sum of sensitivity and specificity were 8.5, 9.4, and 10.1 for F≥2, F≥3, and F = 4, respectively. Using suggested ELF, LSM and FT cutoffs to diagnose F1, F2, F3, and F4, 91 (53.5%), 117 (68.8%), and 110 (64.7%) patients, respectively, were correctly classified according to histological results.ELF demonstrated considerable diagnostic value in fibrosis staging in Asian CHB patients, especially in predicting F≥2. However, LSM consistently provided better performance for predicting F≥3 and F4
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