Publications by authors named "Yun Jung Kim"

81 Publications

Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models.

Sci Rep 2021 06 7;11(1):12004. Epub 2021 Jun 7.

Bioanalytical and Immunoanalytical Research Group, Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea.

Human granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders. We optimized and validated analytical tools by adopting validation parameters for immunogenicity assessment. Using these validated tools, we analyzed serum samples from rats and monkeys injected subcutaneously with GX-G3 (1, 3 or 10 mg/kg once a week for 4 weeks followed by a 4-week recovery period) to determine immunogenicity response and toxicokinetic parameters with serum concentration of GX-G3. Several rats and monkeys were determined to be positive for anti-GX-G3 antibodies. Moreover, the immunogenicity response of GX-G3 was lower in monkeys than in rats, which was relevant to show less inhibition of toxicokinetic profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.
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http://dx.doi.org/10.1038/s41598-021-91360-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184775PMC
June 2021

A Risk Prediction Model for Operative Mortality after Heart Valve Surgery in a Korean Cohort.

J Chest Surg 2021 Apr;54(2):88-98

Department of Thoracic and Cardiovascular Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.

Background: This study aimed to develop a new risk prediction model for operative mortality in a Korean cohort undergoing heart valve surgery using the Korea Heart Valve Surgery Registry (KHVSR) database.

Methods: We analyzed data from 4,742 patients registered in the KHVSR who underwent heart valve surgery at 9 institutions between 2017 and 2018. A risk prediction model was developed for operative mortality, defined as death within 30 days after surgery or during the same hospitalization. A statistical model was generated with a scoring system by multiple logistic regression analyses. The performance of the model was evaluated by its discrimination and calibration abilities.

Results: Operative mortality occurred in 142 patients. The final regression models identified 13 risk variables. The risk prediction model showed good discrimination, with a c-statistic of 0.805 and calibration with Hosmer-Lemeshow goodness-of-fit p-value of 0.630. The risk scores ranged from -1 to 15, and were associated with an increase in predicted mortality. The predicted mortality across the risk scores ranged from 0.3% to 80.6%.

Conclusion: This risk prediction model using a scoring system specific to heart valve surgery was developed from the KHVSR database. The risk prediction model showed that operative mortality could be predicted well in a Korean cohort.
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http://dx.doi.org/10.5090/jcs.20.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038884PMC
April 2021

6-month-olds are sensitive to English morphology.

Dev Sci 2021 07 2;24(4):e13089. Epub 2021 Mar 2.

Department of Linguistics, University of California, Los Angeles, Los Angeles, CA, USA.

Each language has its unique way to mark grammatical information such as gender, number and tense. For example, English marks number and tense/aspect information with morphological suffixes (e.g., -s or -ed). These morphological suffixes are crucial for language acquisition as they are the basic building blocks of syntax, encode relationships, and convey meaning. Previous research shows that English-learning infants recognize morphological suffixes attached to nonce words by the end of the first year, although even 8-month-olds recognize them when they are attached to known words. These results support an acquisition trajectory where discovery of meaning guides infants' acquisition of morphological suffixes. In this paper, we re-evaluated English-learning infants' knowledge of morphological suffixes in the first year of life. We found that 6-month-olds successfully segmented nonce words suffixed with -s, -ing, -ed and a pseudo-morpheme -sh. Additionally, they related nonce words suffixed with -s, but not -ing, -ed or a pseudo-morpheme -sh and stems. By 8-months, infants were also able to relate nonce words suffixed with -ing and stems. Our results show that infants demonstrate knowledge of morphological relatedness from the earliest stages of acquisition. They do so even in the absence of access to meaning. Based on these results, we argue for a developmental timeline where the acquisition of morphology is, at least, concurrent with the acquisition of phonology and meaning.
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http://dx.doi.org/10.1111/desc.13089DOI Listing
July 2021

Stem similarity modulates infants' acquisition of phonological alternations.

Cognition 2021 04 3;209:104573. Epub 2021 Jan 3.

Department of Linguistics, Queen Mary University of London, United Kingdom.

Phonemes have variant pronunciations depending on context. For instance, in American English, the [t] in pat [pæt] and the [d] in pad [pæd] are both realized with a tap [ɾ] when the -ing suffix is attached, [pæɾɪŋ]. We show that despite greater distributional and acoustic support for the [t]-tap alternation, 12-month-olds successfully relate taps to stems with a perceptually-similar final [d], not the dissimilar final-[t]. Thus, distributional learning of phonological alternations is constrained by infants' preference for the alternation of perceptually-similar segments. Further, the ability to relate variant surface forms emerges between 8- and 12-months. Our findings of biased learning provide further empirical support for a role for perceptual similarity in the acquisition of linguistically-relevant categories. We discuss the implications of our findings for phonological theory, language acquisition and models of the mental lexicon.
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http://dx.doi.org/10.1016/j.cognition.2020.104573DOI Listing
April 2021

Pattern and Impact of Off-label Underdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Who are Indicated for Standard Dosing.

Am J Cardiol 2020 05 8;125(9):1332-1338. Epub 2020 Feb 8.

Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

With safety concerns about increasing bleeding, off-label underdosing of non-vitamin K antagonist anticoagulants (NOACs) is common in East Asian patients with atrial fibrillation (AF). We tried to investigate the pattern of NOAC underdosing and associated clinical outcomes in patients with AF who are indicated for standard dosing. Using the Korean National Health Insurance Service database, we evaluated 16,568 patients with a new prescription of NOAC who are indicated for standard NOAC dosing and compared 4,536 patients with warfarin with respect to thromboembolic events (ischemic stroke or systemic embolization), all-cause mortality and major bleeding. Of the 16,568 patients indicated for standard NOAC dosing, 8,549 (51.9%) received off-label underdosing (50.6% rivaroxaban, 53.0% apixaban). During a median follow up of 15.0 months, as compared with warfarin, underdosing of rivaroxaban was associated with lower risks of major thromboembolic events (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.41 to 0.69) and all-cause mortality (HR 0.57, 95% CI: 0.41 to 0.82), and a similar risk of major bleeding (HR 1.10, 95% CI: 0.82 to 1.46). However, underdosing of apixaban was associated with similar risks of major thromboembolic events (HR: 0.90; 95% CI: 0.70 to 1.16), all-cause mortality (HR 0.94, 95 CI: 0.71 to 1.24) and major bleeding (HR 0.84, 95% CI: 0.61 to 1.17). In conclusion, in this Korean population with AF who are indicated for standard NOAC dosing, off-label underdosing is common and its clinical benefit over warfarin was inconsistent according to types of NOAC. Notably, apixaban underdosing provides no benefit in effectiveness compared with warfarin.
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http://dx.doi.org/10.1016/j.amjcard.2020.01.044DOI Listing
May 2020

Tuning Two Interfaces with Fluoroethylene Carbonate Electrolytes for High-Performance Li/LCO Batteries.

ACS Omega 2019 Feb 14;4(2):3220-3227. Epub 2019 Feb 14.

Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.

Various electrolytes have been reported to enhance the reversibility of Li-metal electrodes. However, for these electrolytes, concurrent and balanced control of Li-metal and positive electrode interfaces is a critical step toward fabrication of high-performance Li-metal batteries. Here, we report the tuning of Li-metal and lithium cobalt oxide (LCO) interfaces with fluoroethylene carbonate (FEC)-containing electrolytes to achieve high cycling stability of Li/LCO batteries. Reversibility of the Li-metal electrode is considerably enhanced for electrolytes with high FEC contents, confirming the positive effect of FEC on the stabilization of the Li-metal electrode. However, for FEC contents of 50 wt % and above, the discharge capacity is significantly reduced because of the formation of a passivation layer on the LCO cathodes. Using balanced tuning of the two interfaces, stable cycling over 350 cycles at 1.5 mA cm is achieved for a Li/LCO cell with the 1 M LiPF FEC/DEC = 30/70 electrolyte. The enhanced reversibility of the Li-metal electrode is associated with the formation of LiF and polycarbonate in the FEC-derived solid electrolyte interface (SEI) layer. In addition, electrolytes with high FEC contents lead to lateral Li deposition on the sides of Li deposits and larger dimensions of rodlike Li deposits, suggesting the elastic and ion-conductive nature of the FEC-derived SEI layer.
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http://dx.doi.org/10.1021/acsomega.8b03022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648377PMC
February 2019

Budget Impact Analysis of the Change in Peritoneal Dialysis Use Rate in Korea.

Perit Dial Int 2019 Nov-Dec;39(6):547-552. Epub 2019 Jul 23.

National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea

While the number of peritoneal dialysis (PD) patients has decreased by 14.4% from 2006 to 2016, the number of hemodialysis (HD) patients has sharply increased, by 237.2%, in the same period, leading to an increase in the total medical cost. We analyzed the effects of the changes in PD use rates for dialysis patients in Korea on the healthcare budget using budget impact analysis (BIA).The analysis modeled the influence of the increase in dialysis for the target population, changes in modality use rate, and/or changes in costs per patient-year on total medical cost for patients on dialysis, using the National Health Insurance Service (NHI) claims data. We developed 8 scenarios according to the changing PD use rate.In scenarios 1 - 4 (increase in PD patients by 6%, 13%, 20%, and 50% of non-diabetic prevalent HD patients under 65), 5-year budget savings ranged from $47 million to $394 million (0.9% - 7.3% of the end-stage renal disease [ESRD] budget). In scenarios 5 - 8 (increase in incident PD patients by 20%, 50%, 70%, and 100% of non-diabetic patients under 65), 5-year savings ranged from $25 million to $74 million (0.5% - 1.4% of the ESRD budget). In all scenarios, budget savings were higher as PD patients increased, showing a gradually growing trend.In all scenarios from the payer's perspective, savings could be achieved through an increase in PD use. Selecting PD for ESRD patients without different expected clinical outcomes between HD and PD would be beneficial to the NHI budget.
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http://dx.doi.org/10.3747/pdi.2018.00037DOI Listing
August 2020

Rational Design of Highly Packed, Crack-Free Sulfur Electrodes by Scaffold-Supported Drying for Ultrahigh-Sulfur-Loaded Lithium-Sulfur Batteries.

ACS Appl Mater Interfaces 2019 Aug 6;11(33):29849-29857. Epub 2019 Aug 6.

Department of Chemical and Biomolecular Engineering , Korea Advanced Institute of Science and Technology , 291 Daehak-ro , Yuseong-gu, Daejeon 34141 , Republic of Korea.

Despite the notable progress in the development of rechargeable lithium-sulfur batteries over the last decade, achieving high performance with high-sulfur-loaded sulfur cathodes remains a key challenge on the path to the commercialization of practical lithium-sulfur batteries. This paper presents a novel method by which to fabricate a crack-free sulfur electrode with an ultrahigh sulfur loading (16 mg cm) and a high sulfur content (64%). By introducing a porous scaffold on the top of a cast of sulfur cathode slurry, the formation of cracks during the drying of the cast can be prevented due to the lower volume shrinkage of the skin. The scaffold-supported sulfur cathode delivers a notably high capacities of 10.3 mAh cm and 473 mAh cm after a prolonged cycle, demonstrating that the crack-free structure renders more uniform redox reactions at such high sulfur loading. The highly packed, crack-free feature of the sulfur cathode is advantageous, given that it reduces the electrolyte uptake to as low as an E/S ratio of 4 μL mg, which additionally contributes to the high energy density. Therefore, the scaffold-supported drying fabrication method as presented here provides an effective route by which to design practically viable, energy-dense lithium-sulfur batteries.
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http://dx.doi.org/10.1021/acsami.9b08006DOI Listing
August 2019

Safety and Effectiveness of Contemporary P2Y Inhibitors in an East Asian Population With Acute Coronary Syndrome: A Nationwide Population-Based Cohort Study.

J Am Heart Assoc 2019 07 16;8(14):e012078. Epub 2019 Jul 16.

Division of Cardiology Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea.

Background Prior reports indicate that the effect of P2Y inhibitors may be different in East Asian patients ("East Asian paradox"); therefore, understanding the outcomes associated with potent P2Y inhibitors in different populations is clinically important. Methods and Results In this observational cohort study using administrative healthcare data sets, we compared safety and effectiveness of contemporary P2Y inhibitors in patients with acute coronary syndrome. The primary safety outcomes were major and any bleeding, and the primary effectiveness outcomes were major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) and all-cause mortality. Among 70 715 patients with acute coronary syndrome, 56 216 (79.5%) used clopidogrel, 11 402 (16.1%) used ticagrelor, and 3097 (4.4%) used prasugrel. The median follow-up period was 18.0 months (interquartile range: 9.6-26.4 months). In a propensity-matched cohort, compared with clopidogrel, ticagrelor was associated with a higher risk of any bleeding (hazard ratio: 1.23; 95% CI, 1.14-1.33) but a lower risk of mortality (hazard ratio: 0.76; 95% CI, 0.63-0.91). Prasugrel, compared with clopidogrel, was associated with higher risks of any bleeding (hazard ratio: 1.23; 95% CI, 1.06-1.43) and major bleeding (hazard ratio: 1.50; 95% CI, 1.01-2.21) but a similar risk of effectiveness outcomes. No significant difference was noted between ticagrelor and prasugrel with respect to key safety or effectiveness outcomes. Several sensitivity analyses showed similar results. Conclusions In East Asian patients with acute coronary syndrome, compared with clopidogrel, ticagrelor was associated with an increased risk of bleeding but a decreased risk of mortality. Prasugrel was associated with an increase of any bleeding without difference in effectiveness outcomes. The risks of bleeding and ischemic events were similar between ticagrelor and prasugrel.
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http://dx.doi.org/10.1161/JAHA.119.012078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662138PMC
July 2019

Preclinical evaluation of a biobetter candidate: Pharmacokinetics and pharmacodynamics of GX-G3 in healthy and neutropenia-induced rats.

Drug Dev Res 2019 09 11;80(6):807-813. Epub 2019 Jul 11.

Department of Bio-institute, Genexine, Inc., Seongnam, Gyeonggi, Republic of Korea.

Neutropenia is a condition of an abnormally low number of neutrophils which render patients more susceptible to infections, especially to bacterial infections, as the condition may become life threatening and deadly without prompt medical attention. Various factors such as, anticancer drugs, radiotherapy, infectious diseases, congenital defects, or vitamin B12/B9 deficiency can trigger neutropenia. GX-G3, a human hybrid (hy) Fc-fused granulocyte colony stimulating factor (G-CSF), was developed as next-generation G-CSF for the treatment of cancer therapy-induced neutropenia. In this study, with the aim of investigating this promising potential next-generation G-CSF, comparative pharmacokinetic and pharmacodynamic studies were conducted in healthy and neutropenia-induced rats. It was found that t of GX-G3 is longer than same mass injection of filgrastim and pegfilgrastim and AUEC (area under theeffect-time curve from time zero to the last measurable ANC level) of absolute neutrophil count showed a significant increase after GX-G3 injection compared with filgrastim and pegfilgrastim in healthy rats. Besides, in duration of neutropenia after the same mass injection GX-G3 showed about 3.3 days of reduction effect compared with that of filgrastim, and 1.3 days of reduction effect compared with that of pegfilgrastim in neutropenia-induced rats. These results demonstrate that the half-life of GX-G3 is longer than pegfilgrastim and GX-G3 is more effective than filgrastim and pegfilgrastim in neutropenia-induced rats.
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http://dx.doi.org/10.1002/ddr.21563DOI Listing
September 2019

Time- and Dose-Dependent Association of Statin Use With Risk of Clinically Relevant New-Onset Diabetes Mellitus in Primary Prevention: A Nationwide Observational Cohort Study.

J Am Heart Assoc 2019 04;8(8):e011320

6 Division of Cardiology Asan Medical Center University of Ulsan College of Medicine Seoul Korea.

Background Given that statins are increasingly being used for primary-prevention, the public concerns regarding the risk of new-onset diabetes mellitus associated with statin use may be an issue. Methods and Results Using healthcare data from the national health insurance examinees, our study comprised a cohort of adults aged ≥40 years with hypercholesterolemia who would be eligible for statin therapy for primary prevention from 2005 to 2012. The primary outcome was the occurrence of clinically relevant new-onset diabetes mellitus requiring medical therapy. Among 2 162 119 adults with hypercholesterolemia who might be eligible for statin therapy, 638 625 (29.5%) ever used statins and 1 523 494 (70.5%) never used statins. In the propensity-matched cohort of 518 491 pairs, during mean follow-up of 3.9 years, being an ever-user of statin was significantly associated with diabetes mellitus risk compared with being a never-user of statin (13.4 versus 6.9 per 1000 person-years; adjusted hazard ratio [ HR ], 1.88; 95% CI , 1.85-1.93). With increasing duration of statin use, the risk of diabetes mellitus was proportionally increased ( HR 1.25 <1 year, HR 2.22 for 1-2 years, and HR 2.62 >2 years). An excess risk of diabetes mellitus was also associated with a higher intensity ( HR 1.75 for low-to-moderate potency and HR 2.31 for high potency) and a cumulative dosing of statin ( HR 1.06 for low-tertile, HR 1.74 for middle-tertile, and HR 2.52 for high-tertile of defined-daily-disease). Conclusions In patients receiving statin therapy for primary prevention, there was a time- and dose-dependent association of statin use with an increasing risk of new-onset diabetes mellitus.
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http://dx.doi.org/10.1161/JAHA.118.011320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507181PMC
April 2019

Achieving three-dimensional lithium sulfide growth in lithium-sulfur batteries using high-donor-number anions.

Nat Commun 2019 01 14;10(1):188. Epub 2019 Jan 14.

Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

Uncontrolled growth of insulating lithium sulfide leads to passivation of sulfur cathodes, which limits high sulfur utilization in lithium-sulfur batteries. Sulfur utilization can be augmented in electrolytes based on solvents with high Gutmann Donor Number; however, violent lithium metal corrosion is a drawback. Here we report that particulate lithium sulfide growth can be achieved using a salt anion with a high donor number, such as bromide or triflate. The use of bromide leads to ~95 % sulfur utilization by suppressing electrode passivation. More importantly, the electrolytes with high-donor-number salt anions are notably compatible with lithium metal electrodes. The approach enables a high sulfur-loaded cell with areal capacity higher than 4 mA h cm and high sulfur utilization ( > 90 %). This work offers a simple but practical strategy to modulate lithium sulfide growth, while conserving stability for high-performance lithium-sulfur batteries.
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http://dx.doi.org/10.1038/s41467-018-07975-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331553PMC
January 2019

Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

Stroke 2018 Dec 3:STROKEAHA118023093. Epub 2018 Dec 3.

From the Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea (M.S.C., D.-W.P., G.-B.N.).

Background and Purpose- Limited data are available describing the relative effectiveness, safety, and optimal dosing of non-vitamin K antagonist oral anticoagulants (NOACs) for treatment of nonvalvular atrial fibrillation in East Asian patients. We tried to compare effectiveness and safety outcomes of standard- and low-dose NOACs and warfarin in this population. Methods- Using nationwide administrative claims-based datasets from the Korean National Health Insurance Service Database (July 1, 2015, to December 31, 2016), this study comprised 56 504 anticoagulation-naive nonvalvular atrial fibrillation patients with high thromboembolic risk (CHADS-VASc score, ≥2) treated with oral anticoagulants. Main study outcomes included thromboembolic events (ischemic stroke or systemic embolism), major bleeding, and mortality. Results- Among the study patients, 10 409 (18.4%) received warfarin and 46 095 (81.6%) were treated with NOACs: dabigatran (n=12 593; 22.3%), rivaroxaban (n=21 000; 37.2%), and apixaban (n=12 502; 22.1%). Low-dose NOAC (75.1% dabigatran, 59.7% rivaroxaban, and 62.7% apixaban) was more frequently used than standard-dose NOAC. During median follow-up of 15.0 months, each NOAC was associated with significantly lower risk of thromboembolic events (hazard ratio [HR], 0.76; 95% CI, 0.75-0.81 for dabigatran; HR, 0.74; 95% CI, 0.65-0.83 for rivaroxaban; and HR, 0.68; 95% CI, 0.59-0.78 for apixaban). Regarding safety outcomes, dabigatran (HR, 0.81; CI, 0.69-0.95) and apixaban (HR, 0.67; CI, 0.56-0.79) were associated with lower risk of major bleeding but not with rivaroxaban (HR, 0.96; CI, 0.84-1.11). Among adults <75 years of age without chronic kidney disease, use of low-dose apixaban did not demonstrate clinical benefit over warfarin with respect to thromboembolic events (HR, 0.99; CI, 0.76-1.28) and mortality (HR, 0.85; CI, 0.62-1.16). Conclusions- In this cohort of East Asian patients with nonvalvular atrial fibrillation, NOACs were associated with better effectiveness and safety outcomes versus warfarin. Lower NOAC doses were more often used, but an unjustified underdosing of apixaban seems to result in lower clinical benefit.
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http://dx.doi.org/10.1161/STROKEAHA.118.023093DOI Listing
December 2018

Oleic acid enhances keratinocytes differentiation via the upregulation of miR-203 in human epidermal keratinocytes.

J Cosmet Dermatol 2019 Feb 11;18(1):383-389. Epub 2018 Apr 11.

Agricultural Chemistry, College of Agriculture & Life Sciences, Chonnam National University, Gwangju, Korea.

Background: Oleic acid (OA) is an unsaturated free fatty acid (FFA) constituent of sebum. FFAs modulate keratinocyte differentiation. In this study, we determined whether OA affects keratinocyte differentiation in neonatal human epidermal keratinocytes (HEKn).

Methods: HEKn was grown in EpiLife medium. The cells were treated with various concentrations of OA. The expression levels of keratin 10 and involucrin were determined using Western blotting (for the proteins) and quantitative real time polymerase chain reaction (qRT-PCR) (for the mRNAs). Cytoskeletal changes were investigated by immunofluorescent staining. The levels of microRNA (miR)-203 were determined by stem-loop qRT-PCR. The effect of miR-203 on keratinocyte differentiation was evaluated using anti-miR-203.

Results: Treatment with OA promoted the expression of keratin 10 and involucrin, which are markers of spinous and granular layer keratinocytes, respectively. Treatment with OA also induced cell stratification and cytoskeletal changes such as the concentric ring organization of actin, a loss of planar polarity, and increased localization of epithelial cadherin (E-cadherin) at cell-cell contacts. OA increased the expression of miR-203, which is associated with keratinocyte differentiation, and reduced the expression of p63, a target of miR-203, in HEKn. Furthermore, transfection with anti-miR-203 suppressed the OA-induced expression of involucrin.

Conclusions: Oleic acid accelerates keratinocyte differentiation via the upregulation of miR-203 in HEKn under sub-confluent conditions.
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http://dx.doi.org/10.1111/jocd.12543DOI Listing
February 2019

Inhaled bronchodilators and acute myocardial infarction: a nested case-control study.

Sci Rep 2017 12 20;7(1):17915. Epub 2017 Dec 20.

National Evidence-based Healthcare Collaborating Agency, Namsan Square (Kukdong B/D) 173 Toegye-Ro, Jung-Gu, Seoul, 04554, Republic of Korea.

We investigated the association between the use of inhaled bronchodilators and the risk of AMI. A nested case-control study using the nationwide insurance claims database was conducted. Overall, 11,054 AMI cases and 47,815 matched (up to 1:5) controls were identified from 1,036,119 subjects without acute major cardiovascular events in the past year. Long-acting and short-acting β-agonists (LABAs and SABAs) were associated with increase in the risk of AMI, although an inhaled corticosteroid combined with a long-acting β-agonist was not. Long-acting muscarinic antagonists (LAMAs) in a dry powder inhaler (DPI) were significantly associated with reduced risk of AMI, while LAMAs in a soft mist inhaler (SMI) didn't decrease the risk of it. In hypertensive or diabetic patients, LAMAs in a DPI were associated with reduced risk of AMI, but LABAs were associated with increased risk. Among the β-blocker users, the reduction of AMI risk by LAMAs was the most significant. In conclusions, inhaled β-agonists were associated with increase in the risk of AMI, while LABAs accompanied by ICSs were not associated with increase in the risk of AMI. LAMAs in a DPI use were associated with lower risk of AMI.
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http://dx.doi.org/10.1038/s41598-017-17890-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738390PMC
December 2017

Mutation of the cyclic di-GMP phosphodiesterase gene in Burkholderia lata SK875 attenuates virulence and enhances biofilm formation.

J Microbiol 2017 Oct 28;55(10):800-808. Epub 2017 Sep 28.

Department of Animal Science and Technology, Konkuk University, Seoul, 05029, Republic of Korea.

Burkholderia sp. is a gram-negative bacterium that commonly exists in the environment, and can cause diseases in plants, animals, and humans. Here, a transposon mutant library of a Burkholderia lata isolate from a pig with swine respiratory disease in Korea was screened for strains showing attenuated virulence in Caenorhabditis elegans. One such mutant was obtained, and the Tn5 insertion junction was mapped to rpfR, a gene encoding a cyclic di-GMP phosphodiesterase that functions as a receptor. Mutation of rpfR caused a reduction in growth on CPG agar and swimming motility as well as a rough colony morphology on Congo red agar. TLC analysis showed reduced AHL secretion, which was in agreement with the results from plate-based and bioluminescence assays. The mutant strain produced significantly more biofilm detected by crystal violet staining than the parent strain. SEM of the mutant strain clearly showed that the overproduced biofilm contained a filamentous structure. These results suggest that the cyclic di-GMP phosphodiesterase RpfR plays an important role in quorum sensing modulation of the bacterial virulence and biofilm formation.
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http://dx.doi.org/10.1007/s12275-017-7374-7DOI Listing
October 2017

Enhancing the Cycling Stability of Sodium Metal Electrodes by Building an Inorganic-Organic Composite Protective Layer.

ACS Appl Mater Interfaces 2017 Feb 9;9(7):6000-6006. Epub 2017 Feb 9.

Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology , 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.

Owing to the natural abundance of sodium resources and their low price, next-generation batteries employing an Na metal anode, such as Na-O and Na-S systems, have attracted a great deal of interest. However, the poor reversibility of an Na metal electrode during repeated electrochemical plating and stripping is a major obstacle to realizing rechargeable sodium metal batteries. It mainly originates from Na dendrite formation and exhaustive electrolyte decomposition due to the high reactivity of Na metal. Herein, we report a free-standing composite protective layer (FCPL) for enhancing the reversibility of an Na metal electrode by mechanically suppressing Na dendritic growth and mitigating the electrolyte decomposition. A systematic variation of the liquid electrolyte uptake of FCPL verifies the existence of a critical shear modulus for suppressing Na dendrite growth, being in good agreement with a linear elastic theory, and emphasizes the importance of the ionic conductivity of FCPL for attaining uniform Na plating and stripping. The Na-Na symmetric cell with an optimized FCPL exhibits a cycle life two times longer than that of a bare Na electrode.
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http://dx.doi.org/10.1021/acsami.6b14437DOI Listing
February 2017

Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea.

Oncotarget 2017 Feb;8(6):9587-9596

Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.

Background: Preclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection.

Results: A total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611-0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047).

Materials And Methods: Data were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival.

Conclusions: This large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.
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http://dx.doi.org/10.18632/oncotarget.14525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354755PMC
February 2017

Structural modulation of lithium metal-electrolyte interface with three-dimensional metallic interlayer for high-performance lithium metal batteries.

Sci Rep 2016 08 3;6:30830. Epub 2016 Aug 3.

Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

The use of lithium (Li) metal anodes has been reconsidered because of the necessity for a higher energy density in secondary batteries. However, Li metal anodes suffer from 'dead' Li formation and surface deactivation which consequently form a porous layer of redundant Li aggregates. In this work, a fibrous metal felt (FMF) as a three-dimensional conductive interlayer was introduced between the separator and the Li metal anode to improve the reversibility of the Li metal anode. The FMF can facilitate charge transfer in the porous layer, rendering it electrochemically more active. In addition, the FMF acted as a robust scaffold to accommodate Li deposits compactly in its interstitial sites. The FMF-integrated Li metal (FMF/Li) electrode operated with a small polarisation even at a current density of 10 mA cm(-2), and it exhibited a seven times longer cycle-life than that of an FMF-free Li electrode in a symmetric cell configuration. A Li metal battery (LMB) using the FMF/Li electrode and a LiFePO4 electrode exhibited a two-fold increase in cycling stability compared with that of a bare Li metal electrode, demonstrating the practical effectiveness of this approach for high performance LMBs.
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http://dx.doi.org/10.1038/srep30830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971473PMC
August 2016

The effects of inhaled respiratory drugs on the risk of stroke: A nested case-control study.

Pulm Pharmacol Ther 2016 10 11;40:7-14. Epub 2016 Jul 11.

National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea. Electronic address:

Although there have been concerns that inhaled long-acting muscarinic antagonists increase the risk of stroke, controversies exist. We investigated whether respiratory drugs including long-acting muscarinic antagonists are associated with the risk of stroke. A nested case-control study using the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea) was conducted. Overall, 16,354 stroke cases and 74,451 matched (up to 1:5) controls were identified from 809,684 subjects without acute major cardiovascular events in the past year between January 1, 2010, and December 31, 2011. To determine whether the use of inhaled respiratory drugs is associated with the risk of stroke, conditional logistic regression analysis adjusted by comorbidities, cardiovascular drugs and healthcare utilization was performed. After adjusting for covariates, there were no statistically significant effects of the inhaled drugs on stroke incidence, except for inhaled corticosteroids without a long-acting β2-agonists, which was significantly associated with hemorrhagic stroke. Inhaled respiratory medications, including long-acting muscarinic antagonists, did not affect the risk of stroke in the inhaled respiratory drug users.
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http://dx.doi.org/10.1016/j.pupt.2016.07.002DOI Listing
October 2016

Predictors of False-Negative Results from Percutaneous Transthoracic Fine-Needle Aspiration Biopsy: An Observational Study from a Retrospective Cohort.

Yonsei Med J 2016 Sep;57(5):1243-51

Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: We investigated factors predictive of false-negative pulmonary lesions with nonspecific benign cytology results on percutaneous transthoracic fine-needle aspiration biopsy (FNAB).

Materials And Methods: We included 222 pulmonary lesions that had a nonspecific benign result from percutaneous transthoracic FNAB between March 2005 and December 2012, and were confirmed by subsequent pathologic results or adequate clinical follow up over at least 2 years. Clinical, imaging, and biopsy procedure-related findings were compared between lesions with a final diagnosis of malignancy (false-negative) and lesions with a benign diagnosis (true-negative). Multivariate logistic regression analysis was performed to identify significant predictors of false-negatives.

Results: Of 222 lesions, 115 lesions were proved to be false-negatives, and 107 were true-negatives. Compared with the true-negatives, false-negative lesions showed significantly older age (p=0.037), higher maximum standardized uptake value (SUVmax) on positron emission tomography (p=0.001), larger lesion size (p=0.007), and lesion characteristics of a subsolid nodule (p=0.007). On multivariate logistic regression analysis, SUVmax, lesion size, and lesion characteristics were significant predictors of false-negative results.

Conclusion: Among the clinical, radiologic, and procedure-related factors analyzed, high SUVmax, large lesion size, and subsolid lesions were useful for predicting malignancy in pulmonary lesions with nonspecific benign cytology results on FNAB.
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http://dx.doi.org/10.3349/ymj.2016.57.5.1243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960393PMC
September 2016

Level of Blood Pressure Control and Cardiovascular Events: SPRINT Criteria Versus the 2014 Hypertension Recommendations.

J Am Coll Cardiol 2016 Jun;67(24):2821-31

Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine and National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea. Electronic address:

Background: Blood pressure (BP) targets from the SPRINT (Systolic Blood Pressure Intervention Trial) differ from targets of the 2014 hypertension (HTN) recommendations of the Eighth Joint National Committee.

Objectives: The goal of this study was to estimate the proportion of hypertensive adults with who would meet BP goals under the SPRINT criteria and under the 2014 recommendations, and to determine related effects on cardiovascular morbidity and mortality.

Methods: We used data from the Korean National Health and Nutrition Examination Survey of 2008 to 2013 (n = 13,346), as well as the Korean National Health Insurance Service health examinee cohort of 2007 (n = 67,965), to estimate the proportion of subjects meeting BP goals of each of the criteria. Using data from the Korean National Health Insurance Service health examinee cohort of 2007 (n = 67,965), we compared risks of major cardiovascular events (composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) associated with different BP control goals.

Results: A substantially lower proportion of hypertensive adults met BP goals of the SPRINT criteria compared with the 2014 recommendations (11.9% vs. 70.8%, respectively). Ten-year predicted cardiovascular risks were lowest in the intensive control group (below SPRINT BP goals), intermediate in the less-intensive group (above SPRINT goals but below 2014 recommendation goals), and highest in the uncontrolled group (above 2014 recommendations) (6.15%, 7.65%, and 9.39%, respectively; p < 0.001). After multivariable adjustment, the less-intensive and uncontrolled groups had a greater risk of major cardiovascular events (hazard ratios 1.17 and 1.62, respectively; p value for trend, <0.001) than the intensive group.

Conclusions: Substantially fewer hypertensive adults would meet SPRINT BP goals than would meet 2014 recommendation goals. Stricter BP control is associated with a decreased risk of major cardiovascular events.
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http://dx.doi.org/10.1016/j.jacc.2016.03.572DOI Listing
June 2016

Inhaled Corticosteroids Use Is Not Associated With an Increased Risk of Pregnancy-Induced Hypertension and Gestational Diabetes Mellitus: Two Nested Case-Control Studies.

Medicine (Baltimore) 2016 May;95(22):e3627

From the National Evidence-Based Healthcare Collaborating Agency (C-HL, JK, EJJ, YJK, SC, DKK, J-JY, HIY); Division of Pulmonary and Critical Care Medicine (C-HL, J-JY), Department of Internal Medicine, Seoul National University College of Medicine; Department of Obstetrics and Gynecology (J-HL), Seoul National University College of Medicine, Seoul National University Hospital; Division of Pulmonary and Critical Care Medicine (DKK), Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center; Division of Pulmonary and Critical Care Medicine (HIY), Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam-Si, Republic of Korea; and Department of Health Policy and Hospital Management, Graduate School of Public Health, Korea University (JK).

There have been concerns that systemic corticosteroid use is associated with pregnancy-induced hypertension (PIH) and diabetes mellitus. However, the relationship between inhaled corticosteroids (ICSs) and the risk of PIH has not been fully examined, and there was no study investigating the association between ICS use and the development of gestational diabetes mellitus (GDM). The aims of the study are to determine whether the use of ICSs during pregnancy increases the risk of PIH and GDM in women.We conducted 2 nested case-control studies utilizing the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea), in which 1,306,281 pregnant women who delivered between January 1, 2009 and December 31, 2011 were included. Among them, PIH cases and GDM cases were identified and matched controls were included. Conditional logistic regression analyses adjusted by other concomitant drugs use during and before pregnancy and confounding covariates including comorbidities were performed.Total 43,908 PIH cases and 219,534 controls, and 34,190 GDM cases and 170,934 control subjects were identified. When other concomitant drugs use during pregnancy was adjusted, ICS use was associated with an increased rate of PIH (adjusted odds ratio, 1.40 [95% CI, 1.05-1.87]). ICS medication possession ratios and cumulative doses were associated with an increased risk of PIH. However, the statistical significance was not found in other models. In both unadjusted and adjusted multivariable models, ICSs use was not associated with increase in the risk of GDM.ICSs use is not associated with an increased risk of PIH and GDM.
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http://dx.doi.org/10.1097/MD.0000000000003627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900701PMC
May 2016

Association of Metformin Use With Cancer-Specific Mortality in Hepatocellular Carcinoma After Curative Resection: A Nationwide Population-Based Study.

Medicine (Baltimore) 2016 Apr;95(17):e3527

From the Department of Radiation Oncology (Y-SS, M-SK, WIJ), Korea Institute of Radiological and Medical Sciences; Division for Healthcare Technology Assessment Research (Y-JK, M-SK, SHK, HJT, CMP, AJJ, HJK, JAC, MJK), National Evidence-based Healthcare Collaborating Agency; Department of General Surgery (K-SS), Seoul National University Hospital; Department of General Surgery (SBK); Department of Internal Medicine (CJH, YJK), Korea Institute of Radiological and Medical Sciences; Department of Anatomy (HJC), Seoul National University College of Medicine, Seoul, Korea; and Department of Oncology (MNP), McGill University, Montreal, QC, Canada.

Many preclinical reports and retrospective population studies have shown an anticancer effect of metformin in patients with several types of cancer and comorbid type 2 diabetes mellitus (T2DM). In this work, the anticancer effect of metformin was assessed in hepatocellular carcinoma (HCC) patients with T2DM who underwent curative resection.A population-based retrospective cohort design was used. Data were obtained from the National Health Insurance Service and Korea Center Cancer Registry in the Republic of Korea, identifying 5494 patients with newly diagnosed HCC who underwent curative resection between 2005 and 2011. Crude and adjusted hazard ratios (HRs) were calculated using Cox proportional hazard models to estimate effects. In the sensitivity analysis, we excluded patients who started metformin or other oral hypoglycemic agents (OHAs) after HCC diagnosis to control for immortal time bias.From the patient cohort, 751 diabetic patients who were prescribed an OHA were analyzed for HCC-specific mortality and retreatment upon recurrence, comparing 533 patients treated with metformin to 218 patients treated without metformin. In the fully adjusted analyses, metformin users showed a significantly lower risk of HCC-specific mortality (HR 0.38, 95% confidence interval [CI] 0.30-0.49) and retreatment events (HR 0.41, 95% CI 0.33-0.52) compared with metformin nonusers. Risks for HCC-specific mortality were consistently lower among metformin-using groups, excluding patients who started metformin or OHAs after diagnosis.In this large population-based cohort of patients with comorbid HCC and T2DM, treated with curative hepatic resection, metformin use was associated with improvement of HCC-specific mortality and reduced occurrence of retreatment events.
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http://dx.doi.org/10.1097/MD.0000000000003527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998724PMC
April 2016

ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis.

Elife 2016 04 13;5. Epub 2016 Apr 13.

Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.

The endosomal sorting complexes required for transport (ESCRT) pathway facilitates multiple fundamental membrane remodeling events. Previously, we determined X-ray crystal structures of ESCRT-III subunit Snf7, the yeast CHMP4 ortholog, in its active and polymeric state (Tang et al., 2015). However, how ESCRT-III activation is coordinated by the upstream ESCRT components at endosomes remains unclear. Here, we provide a molecular explanation for the functional divergence of structurally similar ESCRT-III subunits. We characterize novel mutations in ESCRT-III Snf7 that trigger activation, and identify a novel role of Bro1, the yeast ALIX ortholog, in Snf7 assembly. We show that upstream ESCRTs regulate Snf7 activation at both its N-terminal core domain and the C-terminus α6 helix through two parallel ubiquitin-dependent pathways: the ESCRT-I-ESCRT-II-Vps20 pathway and the ESCRT-0-Bro1 pathway. We therefore provide an enhanced understanding for the activation of the spatially unique ESCRT-III-mediated membrane remodeling.
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http://dx.doi.org/10.7554/eLife.15507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865371PMC
April 2016

Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer.

BMC Cancer 2016 Mar 16;16:224. Epub 2016 Mar 16.

Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background: EGFR mutation-induced cell proliferation causes changes in tumor biology and tumor metabolism, which may reflect tumor marker concentration and 18F-FDG uptake on PET/CT. Direct aspirates of primary lung tumors contain different concentrations of tumor markers than serum tumor markers, and may correlate better with EGFR mutation than serum tumor markers. The purpose of this study is to investigate an association between cytologic tumor markers and FDG uptake with EGFR mutation status in non-small cell lung cancer (NSCLC).

Methods: We prospectively collected tumor aspirates of 61 patients who underwent EGFR mutation analysis. Serum and cytologic CYFRA 21-1, CEA, and SCCA levels were measured and correlated with EGFR gene mutations. FDG PET/CT was performed on 58 patients for NSCLC staging, and SUV was correlated with EGFR mutation status.

Results: Thirty (50%) patients had EGFR mutation and 57 patients had adenocarcinoma subtype. Univariate analysis showed that female gender, never smoker, high levels of cytologic CYFRA 21-1 (c-CYFRA) and lower maximum standard uptake value (SUVmax) were correlated with EGFR mutations. ROC generated cut-off values of 20.8 ng/ml for c-CYFRA and SUVmax of 9.6 showed highest sensitivity for EGFR mutation detection. Multivariate analysis revealed that female gender [hazard ratio (HR): 18.15, p = 0.025], higher levels of c-CYFRA (HR: 7.58, and lower SUVmax (HR: 0.08, p = 0.005) were predictive of harboring EGFR mutation.

Conclusions: The cytologic tumor marker c-CYFRA was positively associated with EGFR mutations in NSCLC. EGFR mutation-positive NSCLCs have relatively lower glycolysis compared with NSCLCs without EGFR mutation.
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http://dx.doi.org/10.1186/s12885-016-2251-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793740PMC
March 2016

Sustainable Redox Mediation for Lithium-Oxygen Batteries by a Composite Protective Layer on the Lithium-Metal Anode.

Adv Mater 2016 Feb 2;28(5):857-63. Epub 2015 Dec 2.

Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, South Korea.

A synergic combination of a soluble -redox mediator and a protected Li metal -electrode to prevent the self-discharge of the redox mediator is realized by -exploiting a 2,2,6,6-tetramethylpiperidinyl 1-oxyl (TEMPO) redox mediator and an Al2 O3 /PVdF-HFP composite -protective layer (CPL). Stabilization of Li metal by simple CPL coating is effective at -suppressing the chemical reduction of the oxidized TEMPO and opens up the possibility of sustainable redox mediation for robust cycling of Li-O2 batteries.
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http://dx.doi.org/10.1002/adma.201503169DOI Listing
February 2016

Factors affecting computed tomography image quality for assessment of mechanical aortic valves.

Int J Cardiovasc Imaging 2016 Jun 1;32 Suppl 1:63-71. Epub 2015 Dec 1.

Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea.

Evaluating mechanical valves with computed tomography (CT) can be problematic because artifacts from the metallic components of valves can hamper image quality. The purpose of this study was to determine factors affecting the image quality of cardiac CT to improve assessment of mechanical aortic valves. A total of 144 patients who underwent aortic valve replacement with mechanical valves (ten different types) and who underwent cardiac CT were included. Using a four-point grading system, the image quality of the CT scans was assessed for visibility of the valve leaflets and the subvalvular regions. Data regarding the type of mechanical valve, tube voltage, average heart rate (HR), and HR variability during CT scanning were compared between the non-diagnostic (overall image quality score ≤2) and diagnostic (overall image quality score >2) image quality groups. Logistic regression analyses were performed to identify predictors of non-diagnostic image quality. The percentage of valve types that incorporated a cobalt-chrome component (two types in total) and HR variability were significantly higher in the non-diagnostic image group than in the diagnostic group (P < 0.001 and P = 0.013, respectively). The average HR and tube voltage were not significantly different between the two groups (P > 0.05). Valve type was the only independent predictor of non-diagnostic quality. The CT image quality for patients with mechanical aortic valves differed significantly depending on the type of mechanical valve used and on the degree of HR variability.
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http://dx.doi.org/10.1007/s10554-015-0817-5DOI Listing
June 2016

Healthcare utilisation by pregnant patients with asthma in South Korea: a cohort study using nationwide claims data.

BMJ Open 2015 Nov 6;5(11):e008416. Epub 2015 Nov 6.

Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea, Seoul, Republic of Korea Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam-Si, Republic of Korea.

Objectives: Few nationwide population-based studies have examined the burden of asthma during pregnancy. Here, we investigated the burden and medical treatment of asthma during pregnancy requiring healthcare utilisation in South Korea.

Design: Cohort study.

Setting: Nationwide insurance claims database.

Participants: A total of 1,306,281 pregnant women who delivered in South Korea in 2009-2011.

Outcomes: The prevalence and exacerbation rates of asthma requiring healthcare utilisation, and the prescription of antiasthmatic drugs during pregnancy.

Results: The prevalence of asthma requiring healthcare utilisation was 0.43% among pregnant women. Among those with asthma requiring healthcare utilisation, 6.9% were hospitalised and treated with systemic steroids and short-acting β2-agonists during pregnancy. Oral drugs were prescribed less during the third trimester than during the first trimester (all p values for trends were <0.001). A significant number of patients with asthma were likely to stop taking antiasthmatic drugs after becoming pregnant.

Conclusions: The prevalence of asthma requiring healthcare utilisation during pregnancy was not very high. However, a significant number of women were likely to stop taking antiasthmatic drugs, and those who did tended to experience exacerbations.
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http://dx.doi.org/10.1136/bmjopen-2015-008416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636627PMC
November 2015

Clinical application and potential effects of 2014 hypertension guidelines on incident cardiovascular events.

Am Heart J 2015 Nov 30;170(5):1042-1049.e5. Epub 2015 Jul 30.

Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine and National Evidence-based Healthcare Collaborating Agency, Seoul, Korea. Electronic address:

Background: The applicability to real-world hypertensive patients and the potential effects on future cardiovascular events of the 2014 hypertension guidelines of the Eighth Joint National Committee (JNC-8) remain to be determined.

Methods: Using the Korean National Health and Nutrition Examination Survey of 2008 to 2012 (n = 30,697), we estimated the proportion of Korean adults eligible for hypertension therapy under the 2014 JNC-8 and previous JNC-7 guidelines and the changes affected by the 2014 guidelines. Using the validation cohort (n = 116,767) from the 2003 National Health Examination with 7 years of follow-up, we determined the clinical effects of recent recommendations changes on incident cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke).

Results: Compared with the JNC-7 guidelines, the 2014 guidelines would decrease the number of adults eligible for hypertension therapy from 10.1 million (28.2%) to 9.3 million (25.9%). In the validation cohort, compared with nonhypertensive adults, those eligible for hypertension therapy under the JNC-7 or JNC-8 guidelines had significantly higher risks of cardiovascular events (hazard ratio [HR], 5.05; 95% confidence interval [CI], 4.58-5.57, P < 0.001; and HR, 5.11; 95% CI, 4.63-5.64, P < 0.001, respectively). In addition, adults newly ineligible for treatment under the 2014 guidelines had an increased risk of cardiovascular events relative to nonhypertensive adults (HR, 4.36; 95% CI, 3.65-5.20; P < 0.001).

Conclusions: The 2014 hypertension guidelines would modestly decrease the proportion of Korean adults eligible for hypertension therapy. Adults newly ineligible for hypertension therapy by the 2014 guidelines have a higher risk of cardiovascular events compared to nonhypertensive adults. Our observations should be confirmed or refuted through large, randomized clinical trials.
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http://dx.doi.org/10.1016/j.ahj.2015.07.028DOI Listing
November 2015
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