A randomized, open-label study comparing low-dose clevudine plus adefovir combination therapy with clevudine monotherapy in naïve chronic hepatitis B patients

PURPOSE: Clevudine 30 mg showed potent antiviral activity with a marked post-treatment antiviral effect. However, long-term treatment with clevudine monotherapy induced resistance and myopathy in some cases. The objective of this study is to evaluate the preliminary efficacy and safety of the combination of clevudine 20 mg and adefovir compared to clevudine monotherapy. METHODS: Seventy-four patients were randomized to either a combination of clevudine 20 mg and adefovir or clevudine 20 or 30 mg and were treated for 2 years. The viral kinetics for 24 weeks, virological response [VR; hepatitis B virus (HBV) DNA less than 300 copies/ml], and the biochemical response [BR; normal alanine aminotransferase (ALT)] were assessed. RESULTS: There was no difference in baseline characteristics among the three groups. Viral kinetics study showed no statistically significant difference among them during 24 weeks. The combination group showed 95 % virological response with a statistically significant difference compared to the clevudine 30 mg (67 %) and 20 mg (71 %) groups (p = 0.0376). Biochemical response rates were similar in all groups (78–94 %). No resistance was reported in the combination group, while 20 % of patients treated with clevudine 30 mg or 20 mg reported resistance during 2 years. Muscle-related symptoms such as myalgia (1 in clevudine 30 mg, 1 in the combination group) and muscle weakness (1 in clevudine 30 mg, 2 in clevudine 20 mg) were reported in five patients (7 %); of these, three patients discontinued the study. CONCLUSION: We concluded that the combination of clevudine 20 mg and adefovir produced a potent antiviral response together with a good resistance profile compared to clevudine monotherapy at 96 weeks in this pilot study

Predictive Value of Pharyngeal Width at Rest (JOSCYL Width) for Aspiration in Elderly People

Objective To develop a new tool for aspiration risk prediction based on pharyngeal width at rest in older adults with symptoms of aspiration. Methods Lateral cervical spine roentgenograms were obtained from 33 older adult patients who complained of dysphagia and from 33 healthy, age-matched controls. Pharyngeal width at rest was measured at two points. We named the average of these two pharyngeal widths ‘JOSCYL Width’, calculated ‘JOSCYL Scale’, and compared these parameters between dysphagia and control groups. Correlations of individual JOSCYL Width and JOSCYL Scale, with Penetration Aspiration Scale (PAS) and Dysphagia Outcome and Severity Scale (DOSS) scores were analyzed for the dysphagia group. To determine optimal cutoff points for predicting aspiration, a receiver operating characteristic curve analysis was performed on JOSCYL Width and JOSCYL Scale. Results Both JOSCYL Width and JOSCYL Scale of the dysphagia group were larger than those of the control group (p<0.001). The correlation between JOSCYL Width and severity of dysphagia was significant for the dysphagia group (PAS p=0.007; DOSS p=0.012). The correlation between JOSCYL Scale and the severity of dysphagia was also significant for the dysphagia group (PAS p=0.009; DOSS p=0.011). Optimal cutoffs for JOSCYL Width and JOSCYL Scale for predicting aspiration were 20.0 mm and 5.9, respectively. Conclusion JOSCYL Width and JOSCYL Scale can be new indicators for predicting aspiration in older adults. They are both precise and easy to use

Anti-Skin Aging Effect of Syriacusins from Hibiscus Syriacus on Ultraviolet-Irradiated Human Dermal Fibroblast Cells

Abstract -Photosensitized peroxidation of membrane lipids has been implicated in skin pathologies such as phototoxicity and premature aging. We have previously reported that syriacusin compounds isolated from Hibiscus Syriacus inhibited lipid peroxidation. Here, we investigated whether syriacusins could be effective inhibitor to skin aging using ultraviolet-irradiated human dermal fibroblast cells (HDFCs). Syriacusins A, B, and C inhibit the activity of human neutrophil elastase (HNE), a serine protease to degrade extracellular matrix (ECM) proteins including elastin, with IC50s of 8.0, 5.2, and 6.1 μM, respectively. No changes in cell viability were detected by syriacusins A and B in UV-B (10 mJ/cm 2 ) irradiated HDFCs. Matrix metalloproteinase (MMP)-1 expression in HDFCs was increased by UV-B irradiation. MMP-1 expression in UV-B irradiated HDFCs was decreased by 10 μM and 20 μM syriacusin A to 50% and 20% of untreated control, respectively. Syriacusin B treated with 20 μM reduced MMP-1 expression in UV-B irradiated HDFCs to 60% of untreated control. Syriacusin A also inhibited MMP-2 expression accompanying the increase of type-I pro-collagen in UV-B irradiated HDFCs. These results demonstrate that syriacusin A could be a more effective compound to inhibit skin aging caused by UV irradiation. It suggests that syriacusins A and B might be developed as possible agents to treat or prevent skin aging

Low roll-off of efficiency at high current density in phosphorescent organic light emitting diodes

The authors demonstrate that the reduction of quantum efficiency with increasing current density in phosphorescent light emitting diodes (PhOLEDs) is related to the formation of excitons in hole transporting layer based on the analysis of emission spectra and exciton formation zone. Low roll-off of efficiency in a PhOLED was achieved using dual emitting layers (D-EMLs) by confining the exciton formation near the interface between the emitting layers. The external quantum efficiency was maintained almost constant up to 22 mA/cm2 (10 000 cd/m2) by adopting the D-EMLs in Ir(ppy)3 based PhOLEDs, resulting in high external quantum efficiency (ext=13.1%) at high luminance.This work was supported by the Ministry of Commerce, Industry and Energy of Korea through the OLED center, Samsung SDI, Dongwoo Finechem, and CKC Program

Ligand binding pocket formed by evolutionarily conserved residues in the glucagon-like peptide-1 (GLP-1) receptor core domain

BACKGROUND : Little is known about the interaction between GLP-1 and the heptahelical core domain of GLP1R. RESULTS : GLP-1 Asp9 and Gly4 interact with the evolutionarily conserved residues in extracellular loop 3. CONCLUSION : Ligand binding pocket formed by evolutionarily conserved residues in the GLP1R core domain. Significance: This study highlights the mechanism underlying high affinity interaction between GLP-1 and the binding pocket of the receptor.http://www.jbc.org2016-02-28hb201

Natural Products in the Prevention of Metabolic Diseases: Lessons Learned from the 20th KAST Frontier Scientists Workshop

The incidence of metabolic and chronic diseases including cancer, obesity, inflammation-related diseases sharply increased in the 21st century. Major underlying causes for these diseases are inflammation and oxidative stress. Accordingly, natural products and their bioactive components are obvious therapeutic agents for these diseases, given their antioxidant and anti-inflammatory properties. Research in this area has been significantly expanded to include chemical identification of these compounds using advanced analytical techniques, determining their mechanism of action, food fortification and supplement development, and enhancing their bioavailability and bioactivity using nanotechnology. These timely topics were discussed at the 20th Frontier Scientists Workshop sponsored by the Korean Academy of Science and Technology, held at the University of Hawaii at Manoa on 23 November 2019. Scientists from South Korea and the U.S. shared their recent research under the overarching theme of Bioactive Compounds, Nanoparticles, and Disease Prevention. This review summarizes presentations at the workshop to provide current knowledge of the role of natural products in the prevention and treatment of metabolic diseases