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Objective: The relationship between impaired fasting glucose (IFG) and risk of cardiovascular disease (CVD) or ischemic heart disease (IHD) varies widely according to sex and ethnicity. We evaluated the relationship between IFG and CVD or IHD among Korean men and women.Research Design and Methods: A total of 408,022 individuals who underwent voluntary private health examinations in 17 centers in South Korea were followed for 10 years. Data regarding CVD or IHD events were obtained from the Korean National Health Insurance database. IFG was categorized as grade 1 (fasting glucose 100-109 mg/dL) or grade 2 (110-125 mg/dL).Results: Incidence rates of CVD (per 100,000 person-years) were 2,203 for diabetes. Age-adjusted hazard ratios (HRs) for CVD were 1.17 (95% CI 1.13-1.20) for grade 1 IFG, 1.30 (1.24-1.35) for grade 2 IFG, and 1.81 (1.75-1.86) for diabetes. The increased risk for women was similar to that of men. Age-adjusted HRs for IHD and ischemic stroke were also significantly increased for men and women with IFG and diabetes. After multivariate adjustment of conventional risk factors (hypertension, dyslipidemia, smoking, obesity, and family history of CVD), the overall risk of CVD was greatly attenuated in all categories. However, the HRs for IHD and ischemic stroke remained significantly increased in men for grade 2 IFG but not in women.Conclusions: In Korea, grade 2 IFG is associated with increased risk of IHD and ischemic stroke, independent of other conventional risk factors, in men but not in women. [ABSTRACT FROM AUTHOR]

By sputtering synthesis of cubicCu3N, which decomposes at moderate temperatures, film growth proceeds with simultaneous nitrogenreemission from inside, leading to the formation of some unusual structures or morphology. Wereport a relief morphology comprising densely packed rosette-like features. The rosettes, typically20 µm in size, show a radial furcation followed by successive bifurcation at∼74°, resulting in a fivefold symmetric structure sometimes. The area expansion ofthe features can be as large as ten per cent with regard to the underlyingbottom. Scanning electron micrographs reveal that it is the gliding ofCu3N nanocrystals along the Cu-rich {111}-planes that is responsible for the unusually large areaexpansion. The gliding and packing along the {111}-planes also explain the bifurcation angleof the ramified rosettes. Such a relief morphology can serve as a template for large-areafabrication of concave structures by inverse duplication, adding to the already abundantinnovative applications of this material. [ABSTRACT FROM AUTHOR]

Objective: To exploring the regulatory effect of miR-29a on the transforming growth factor-β1 (TGF-β1) /Smad homolog 3 (Smad3) pathway during the process of rare earth neodymium oxide (Nd(2)O(3)) induced pulmonary fibrosis in mice. Methods: In March 2021, 72 SPF grade C57/BL6J male mice were selected and randomly divided into a control group, Nd(2)O(3) group, Nd(2)O(3)+miR-29a agomir group, and Nd(2)O(3)+NC agomir group, with 18 mice in each group. The Nd(2)O(3) group, Nd(2)O(3)+miR-29a agomir group, and Nd(2)O(3)+NC agomir group were treated with non exposed tracheal instillation, with a dust concentration of 250 mg/ml and a dust volume of 0.1 ml. The control group was given the same volume of physiological saline. After exposure to Nd(2)O(3), 0.1 ml (5 nmol) of miR-29a agomir was injected into the tail vein of mice in the Nd(2)O(3)+miR-29a agomir group every 3 days, while 0.1 ml of NC agomir was injected into the tail vein of mice in the Nd(2)O(3)+NC agomir group. On the 7 th, 14 th, and 28 th days after dust exposure, 6 mice were killed in each group, and the lung tissue of the mice was taken out. HE staining was used to observe the pathological status of the mouse lung tissue; ELISA method was used to detect the levels of TGF-β1 and connective tissue growth factor (CTGF) in lung tissue; Use qRT-PCR detection method to detect the expression level of TGF-β1 mRNA; Using immunofluorescence assay to detect the expression level of Smad3 in mouse lung tissue; Use bioinformatics websites such as TargetScan7 and miRDB to predict the target gene of miR-29a. When the metrological date were satisfied with normal distribution, Mean±SD was used for comparison between groups, t test was used for two indepent samples, and LSD method was used when the variance was homogeneity in pairwise comparison. Results: HE staining showed that the Nd(2)O(3) group of mice showed obvious infiltration of inflammatory cells and structural disorder of alveoli in the early stage of lung tissue. At 28 days, the collagen fibers in the mouse lung tissue increased and the lung tissue showed fibrotic honeycomb like changes. The degree of pulmonary fibrosis in the Nd(2)O(3)+miR-29a agomir group of mice was significantly reduced; The content of TGF-β1 and CTGF in the lung tissue of mice in the Nd(2)O(3)+miR-29a agomir group was lower than that in the Nd(2)O(3)+NC agomir group ( P <0.05) ; The relative expression level of TGF-β1 in the lung tissue of mice in the Nd(2)O(3)+miR-29a agomir group was lower than that in the Nd(2)O(3)+NC agomir group ( P <0.05) ; The expression level of Smad3 in the nucleus of the Nd(2)O(3)+miR-29a agomir group was lower than that of the Nd(2)O(3)+NC agomir group ( P <0.05). The prediction results of bioinformatics websites have found 152 downstream target genes related to miR-29a, among which FBN1, MAP2K6, KPNB1, COL1A2, SNIP1, LAMC1, and SP1 genes may be related to the regulatory effect of miR-29a on TGF-β1/Smad3 signaling pathway. Conclusion: miR-29a may affect lung fibrosis induced by rare earth Nd(2)O(3) exposure in mice by regulating TGF-β1/Smad3 signaling pathway. Overexpression of miR-29a may inhibit TGF-β1/Smad3 signaling pathway and reduce the degree of pulmonary fibrosis in mice.

BL-11C, a new protein crystallography beamline, is an in-vacuum undulator-based microfocus beamline used for macromolecular crystallography at the Pohang Accelerator Laboratory and it was made available to users in June 2017. The beamline is energy tunable in the range 5.0-20 keV to support conventional single- and multi-wavelength anomalous-dispersion experiments against a wide range of heavy metals. At the standard working energy of 12.659 keV, the monochromated beam is focused to 4.1 µm (V) × 8.5 µm (H) full width at half-maximum at the sample position and the measured photon flux is 1.3 × 10 12  photons s -1 . The experimental station is equipped with a Pilatus3 6M detector, a micro-diffractometer (MD2S) incorporating a multi-axis goniometer, and a robotic sample exchanger (CATS) with a dewar capacity of 90 samples. This beamline is suitable for structural determination of weakly diffracting crystalline substances, such as biomaterials, including protein, nucleic acids and their complexes. In addition, serial crystallography experiments for determining crystal structures at room temperature are possible. Herein, the current beamline characteristics, technical information for users and some recent scientific highlights are described., (open access.)

Brain-computer interface (BCI) is an important tool for rehabilitation and control of an external device (e.g., robot arm or home appliances). Fully reconstruction of upper limb movement from brain signals is one of the critical issues for intuitive BCI. However, decoding of forearm rotation from imagined movements using electroencephalography (EEG) is difficult to decode degree of rotation accurately. In this paper, we reconstructed imagined forearm rotation from low- frequency (0.3-3 Hz) of EEG signals. We selected 20 EEG channel on motor cortex for analysis. Ten healthy subjects participated in our experiment. The subjects performed actual and imagined forearm rotation to reach different targets. We trained a reconstruction decoder which used the EEG signals measured from actual movements and the kinematic information only. Additionally, we applied a long short-term memory (LSTM) network to enhance decoding performances. As a result, we achieved the high correlation performance (Average: 0.67) to decode imagined forearm rotation angle. This result has demonstrated that the reconstruction decoder which is trained by the EEG data from actual movement has effective to decode robustly for the imagined forearm rotation angle.

We have developed an artificially controllable strategy of an electrodeposition process adequate for resistive random-access memory (ReRAM) applications of binary Cu 2 O. Typically, the precise control of OH - ion concentration (the intermediate supplier of oxygen ions) at the electrode's surface decides the overall reaction rate of the Cu 2 O. Here, the suggested Pb and Sb metal additives preferentially contribute to the consumption of OH - ions and the supply of OH - ions, respectively, during the Cu 2 O electrochemical reaction so that the final products are the (200) preferential quadrangular pyramids and the (111) preferential triangular pyramids. Interestingly, the coexistence of Sb/Pb precursors in the Cu electrolytes results in extraordinarily decreased reaction rate from the opposite action of OH - ion utilization as well as intense progressive growth behavior, and the resultant Cu 2 O films consist of crystallized small-size nanoparticles (NPs) in an amorphous-like matrix. In the case of ReRAM applications, while the polycrystalline film induces irregular device performance and the amorphous layer shows an easily irreparable electrical breakdown, our NP-assembled Cu 2 O films from Pb/Sb metal ions reveal the formation of a conduction bridge via phase change to a crystalline filament with no need for forming voltage and with superior electrical stability. It is attributed to the coalescence of crystal NPs into large grains during the set/reset cycle process for the heat dissipation of Joule heating. The Cu 2 O sample prepared with a 3 mM Sb + 3 mM Pb mixture solution exhibits forming-free ReRAM devices with high on/off resistance ratios of 1.2 × 10 4 and long-term electrical/thermal stability.

To date, TiO 2 films prepared by atomic layer deposition are widely used to prepare Cu 2 O nanowire (NW)-based photocathodes with photoelectrochemical (PEC) durability as this approach enables conformal coating and furnishes chemical robustness. However, this common approach requires complicated interlayers and makes the fabrication of photocathodes with reproducible performance and long-term stability difficult. Although sol-gel-based approaches have been well established for coating surfaces with oxide thin films, these techniques have rarely been studied for oxide passivation in PEC applications, because the sol-gel coating methods are strongly influenced by surface chemical bonding and have been mainly demonstrated on flat substrates. As a unique strategy based on solution processing, herein, we suggest a creative solution for two problems encountered in the conformal coating of surfaces with oxide layers: (i) how to effectively prevent corrosion of materials with hydrophilic surfaces by simply using a single TiO 2 surface protection layer instead of a complex multilayer structure and (ii) guaranteeing perfect chemical durability. A Cu(OH) 2 NW can be easily prepared as an intermediate phase by anodization of a Cu metal, where the former inherently possesses a hydrophilic hydroxylated surface and thus, enables thorough coating with TiO 2 precursor solutions. Chemically robust nanowires are then generated as the final product via the phase transformation of Cu(OH) 2 to Cu 2 O via sintering at 600 °C. The coated NWs exhibit excellent PEC properties and a stable performance. Consequently, the perfect chemical isolation of the Cu 2 O NWs from the electrolyte allows a remarkable PEC operation with the maintenance of the initial photocurrent for more than one day.

Background: Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up., Methods: Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4-14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5-<25·0 kg/m(2)., Findings: All-cause mortality was minimal at 20·0-25·0 kg/m(2) (HR 1·00, 95% CI 0·98-1·02 for BMI 20·0-<22·5 kg/m(2); 1·00, 0·99-1·01 for BMI 22·5-<25·0 kg/m(2)), and increased significantly both just below this range (1·13, 1·09-1·17 for BMI 18·5-<20·0 kg/m(2); 1·51, 1·43-1·59 for BMI 15·0-<18·5) and throughout the overweight range (1·07, 1·07-1·08 for BMI 25·0-<27·5 kg/m(2); 1·20, 1·18-1·22 for BMI 27·5-<30·0 kg/m(2)). The HR for obesity grade 1 (BMI 30·0-<35·0 kg/m(2)) was 1·45, 95% CI 1·41-1·48; the HR for obesity grade 2 (35·0-<40·0 kg/m(2)) was 1·94, 1·87-2·01; and the HR for obesity grade 3 (40·0-<60·0 kg/m(2)) was 2·76, 2·60-2·92. For BMI over 25·0 kg/m(2), mortality increased approximately log-linearly with BMI; the HR per 5 kg/m(2) units higher BMI was 1·39 (1·34-1·43) in Europe, 1·29 (1·26-1·32) in North America, 1·39 (1·34-1·44) in east Asia, and 1·31 (1·27-1·35) in Australia and New Zealand. This HR per 5 kg/m(2) units higher BMI (for BMI over 25 kg/m(2)) was greater in younger than older people (1·52, 95% CI 1·47-1·56, for BMI measured at 35-49 years vs 1·21, 1·17-1·25, for BMI measured at 70-89 years; pheterogeneity<0·0001), greater in men than women (1·51, 1·46-1·56, vs 1·30, 1·26-1·33; pheterogeneity<0·0001), but similar in studies with self-reported and measured BMI., Interpretation: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations., Funding: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC-BY license. Published by Elsevier Ltd.. All rights reserved.)

Background: The association between low systolic blood pressure (SBP) and vascular disease is unclear, especially in nonclinical populations., Methods and Results: We studied 1 235 246 individuals who participated in routine medical examinations between 1992 and 1995. The hazard ratios (HRs) were adjusted for potential confounders. During 22.7 million person-years of follow-up, 34 816 individuals died of atherosclerotic vascular diseases. An increase in SBP was directly related to an increase in vascular mortality at SBP above ≈100 mmHg. The group with the lowest SBP (<90 mm Hg) had a higher HR for mortality from atherosclerotic vascular disease (HR, 1.53; 95% confidence interval, 1.15-2.03) in comparison with those with an SBP of 90 to 99 mm Hg. The HR associated with the lowest SBP was 2.54 (95% confidence interval, 1.51-4.29) for ischemic heart disease and 1.21 (95% confidence interval, 0.79-1.85) for stroke. Regarding stroke subtype, mortality from hemorrhagic stroke (HR per 10 mm Hg increase, 0.53; 95% confidence interval, 0.29-0.96), rather than mortality from ischemic stroke (HR per 10 mm Hg increase, 1.00; 95% confidence interval, 0.51-1.97), was inversely associated with SBP when SBP fell to <100 mm Hg. Even when excluding the first 5 years of follow-up, the HRs associated with the lowest SBP did not decrease. The inverse association between SBP and vascular mortality in the range <100 mm Hg tended to be apparent in people aged 60 to 95 years in comparison with individuals aged 30 to 59 years., Conclusions: J-curve associations exist between SBP and vascular mortality, which reach a nadir at ≈100 mm Hg. SBP of <90 mm Hg may portend death from vascular disease, particularly from ischemic heart disease., (© 2016 American Heart Association, Inc.)

Purpose: Using nationwide cancer incidence data, we examined whether the strength of the association of cigarette smoking with lung cancer risk differs according to major histological type and gender, taking account of other risk factors in the Korean population., Methods: The study population derived from government employees and teachers aged 20 years and over who participated in a national health examination program in 1998 or 1999. Total study subjects were 1,357,447. After excluding 1556 subjects who were treated with lung cancer during 1998-2000, we restricted our analysis to 1,355,891 cases. We followed up those 1,355,891 subjects who were cancer-free at baseline until December 31, 2010. The incident cancer cases were identified from the Korea Central Cancer Registry, which is a nationwide hospital-based cancer registry system that includes 94 % of the university hospitals and 96 % of the resident training hospitals of the country., Results: A higher risk for having ever smoked was observed for squamous-cell and small-cell carcinoma in both men and women. Heavy and long-term smokers were at higher risk for these carcinomas. Significant associations with quantity and duration-related factors were observed mainly among men. These findings indicate that smoking is closely related to the risk of squamous-cell and small-cell carcinoma among women as well as men. However, the magnitude of smoking-related lung cancer risk is likely to differ between men and women., Conclusion: The hazard ratios for all types of lung cancer were significantly higher in male current smokers than in male never smokers. In case of women, the hazard ratios for adenocarcinoma were not different between current smokers and never smokers. The hazard ratios we found, however, were lower than those reported in Western countries and in Korea, but consistent with those reported in North-eastern Asian countries.

Background: Although reproductive and hormonal factors - such as early menarche and late menopause - have been reported as independent risk factors for cancer, few studies have examined these factors in East Asian populations., Methods: We performed a large prospective cohort study of 66,466 women. Ovarian hormone exposure was defined as length of time between menarche and menopause. Incidence rates for breast, ovarian, endometrial and cervical cancers were examined separately in relation to reproductive lifespan defined as age at menopause minus age at menarche. Multivariable adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using the Cox proportional hazards model., Results: Women with early menarche were at increased risk for developing breast cancer (HR, 1.57, 95% CI, 1.17-2.10) for age at menarche ≤12 years compared to women with age at menarche ≥17 years. Women with late age at menopause (≥52 years) had increased risks for cancers of the breast (HR, 1.59, 95%CI, 1.11-2.28) and ovary (HR, 3.22, 95% CI, 1.09-9.55) compared to women with early menopause (≤45 years of age). Women with longer duration of ovarian hormone exposure (≥40 years) were at increased risk for developing breast cancer (HR, 2.23, 95% CI, 1.35-3.68) as well as endometrial cancer (p for trend, 0.0209)., Conclusions: We showed that longer reproductive spans are associated with an increased risk of breast and endometrial cancer in Korean women., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

[Purpose] The present study attempted to measure two-point discrimination in the upper extremities of healthy Koreans in their 20's. [Subjects and Methods] Using a three-point esthesiometer, we conducted an experiment with a group of 256 college students (128 male and 128 female), attending N University in Chonan, Republic of Korea. [Results] Females showed two-point discrimination at a shorter distance than males at the following points: (i) 5 cm above the elbow joint, the middle part, and 5 cm below the shoulder joint of the anterior upper arm; (ii) 5 cm above the elbow joint and 5 cm below the shoulder joint of the posterior upper arm; (iii) 5 cm above the front of the wrist joint of the forearm; 5 cm below the elbow joint, the palmar part of the distal interphalangeal joint of the thumb, the dorsal part of the distal interphalangeal joint of the middle and little fingers. It was also found that females showed greater two-point discrimination than males in distal regions rather than proximal regions. [Conclusion] The findings of this study will help establish normal values for two-point discrimination of upper extremities of young Koreans in their 20's.

Elevated serum γ-glutamyltransferase (GGT) is a marker of hepatic injury and is associated with risk of chronic disease. However, the value of GGT as a biomarker for cancer risk remains unclear. Therefore, we evaluated the association of serum GGT with cancer incidence among more than 1.6 million Koreans. We included 1,662,087 Koreans (1,108,121 men and 553,966 women aged 20-95 years) who received health insurance from the National Health Insurance Service and had a biennial medical evaluation between 1995 and 1998. Follow-up was through December 2012. Using Cox proportional hazards models, we adjusted for age, smoking status, alcohol consumption, exercise and body mass index after exclusion of early cases (cancer diagnosis or death within 5 years of starting follow-up) and estimated hazard ratios (HRs) of overall and organ-specific cancer incidence by GGT quintiles. During the 17-year follow-up, 129,087 new cancer cases occurred among the participants. Across levels of GGT, there was a positive gradient of HR and the highest quintile of GGT (≥ 60 IU/L) had the highest HR for all cancers in both men and women. By cancer site, the association was strongest for liver cancer, comparing the highest and lowest strata in men [HR, 6.67; 95% confidence interval (95%CI), 5.88-7.57] and in women (HR, 7.57; 95%CI, 6.41-8.94). Significant associations were also observed for cancers of the esophagus, larynx, stomach, colorectal, bile duct and lung in men and of the bile duct in women. Increased serum GGT level is independently associated with risk of cancer., (© 2015 UICC.)

Objective: Although reproductive and hormonal factors, such as menarche and menopause, have been reported as independent risk factors for atherosclerotic cardiovascular disease (ASCVD), few studies have examined these factors in East Asian populations. In the Korean Heart Study, ASCVD risk related to duration of ovarian hormone exposure was examined in a cohort of 66,104 Korean women., Methods: Study members were recruited from participants of routine health examinations at health promotion centers across South Korea in 1996-2004. Ovarian hormone exposure was defined as duration between menarche and menopause. Incidence rates for ASCVD, stroke, and ischemic heart disease were examined in relation to ovarian hormone exposure., Results: The mean duration of ovarian hormone exposure at study baseline was 33.7 years, and risk for ASCVD was negatively associated with duration. Women with shorter ovarian hormone exposure (<30 y) had a higher risk of developing ASCVD (hazard ratio [HR], 1.30; 95% CI, 1.01-1.68) than women with longer ovarian hormone exposure (35-35 y). In similar comparison groups, women with ovarian hormone exposure shorter than 30 years were at increased risk for developing total stroke (HR, 1.18; 95% CI, 1.00-1.38), thrombotic stroke (HR, 1.30; 95% CI, 1.05-1.61), ischemic heart disease (HR, 1.40; 95% CI, 1.19-1.63), and acute myocardial infarction (HR, 1.73; 95% CI, 1.08-2.47)., Conclusions: Our study provides further confirmation of increased cardiovascular risk with shorter reproductive years. Therefore, women with reduced lifetime ovarian hormone exposure should focus on minimizing ASCVD risk by lifestyle modifications such as smoking avoidance or increased physical activities.

Background and Aims: To evaluate the performance of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Pooled Cohort Equations in the Korean Heart Study (KHS) population and to develop a Korean Risk Prediction Model (KRPM) for atherosclerotic cardiovascular disease (ASCVD) events., Methods: The KHS cohort included 200,010 Korean adults aged 40-79 years who were free from ASCVD at baseline. Discrimination, calibration, and recalibration of the ACC/AHA Equations in predicting 10-year ASCVD risk in the KHS cohort were evaluated. The KRPM was derived using Cox model coefficients, mean risk factor values, and mean incidences from the KHS cohort., Results: In the discriminatory analysis, the ACC/AHA Equations' White and African-American (AA) models moderately distinguished cases from non-cases, and were similar to the KRPM: For men, the area under the receiver operating characteristic curve (AUROCs) were 0.727 (White model), 0.725 (AA model), and 0.741 (KRPM); for women, the corresponding AUROCs were 0.738, 0.739, and 0.745. Absolute 10-year ASCVD risk for men in the KHS cohort was overestimated by 56.5% (White model) and 74.1% (AA model), while the risk for women was underestimated by 27.9% (White model) and overestimated by 29.1% (AA model). Recalibration of the ACC/AHA Equations did not affect discriminatory ability but improved calibration substantially, especially in men in the White model. Of the three ASCVD risk prediction models, the KRPM showed best calibration., Conclusions: The ACC/AHA Equations should not be directly applied for ASCVD risk prediction in a Korean population. The KRPM showed best predictive ability for ASCVD risk., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Although the increased risk of coronary artery disease (CAD) in the patients with idiopathic pulmonary fibrosis (IPF) has been reported, there was few detailed information on the risk factors for CAD in IPF. The aim of this study was to investigate the prevalence of CAD in IPF with analysis of other risk factors., Methods: The subjects were 460 patients (mean age, 65 years; 79% male; 74% current or ex-smoker) diagnosed as IPF at Asan Medical Center and 1,925 controls matched with age, gender, smoking habits, and date of IPF diagnosis from the cohort of Korean Heart Study. Cardiovascular risk factors and prevalence of CAD in both groups were compared and the incidence of newly developed CAD during follow-up was also analyzed., Results: IPF group was more diabetic, and control group had a higher proportion of hypertension and hypercholesterolemia. The prevalence of CAD in IPF group (7%) was two times higher than that of control group (3%). Multivariate analysis revealed that age (OR, 1.04; 95% CI, 1.02-1.07), hypertension (OR, 2.13; 95% CI, 1.36-3.33), hypercholesterolemia (OR, 3.85; 95% CI, 2.51-5.88), and IPF (OR, 2.64; 95% CI, 1.68-4.14) were significant risk factors for CAD. During follow-up (median: 2.5 years for IPF and 4.4 years for controls), the incidence of newly diagnosed CAD was higher in the patients with IPF (6.8%) compared to controls (2.8%) (RR, 1.92; 95% CI, 1.08-3.43)., Conclusions: IPF itself was an independent risk factor for CAD after the adjustment of age, hypertension, diabetes, and hypercholesterolemia.

Alzheimer's disease (AD), a progressive and neurodegenerative disorder of the brain, is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, aurone derivatives were designed and synthesized as AChE inhibitors based on the lead structure of sulfuretin. Of those synthesized, compound 10d showed ca. 1700-fold and 6-fold higher AChE inhibitory activity than sulfuretin and galantamine, respectively. This compound also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2mg/kg., (Copyright © 2014. Published by Elsevier Ltd.)

Background: To describe the rationale, objectives, protocol, and preliminary results for a new prospective cohort study of cardiovascular disease (CVD) risk factors in South Korea., Methods: Study members were recruited from participants in routine health assessments at health promotion centres across South Korea. Established and emerging CVD risk factors were measured. Eighteen centres holding electronic health records agreed to linkage of participants' records to future health insurance claims for monitoring of disease events. The recruitment of 430,920 participants (266,782 men, 164,138 women), aged 30-74 years, provides broad geographical reach across South Korea., Results: Risk factor prevalence was more favourable in women than men, and, in general, in the younger rather than older study members. There was also close similarity between the characteristics of the present sample and the Korean National Health and Nutrition Examination Survey. The expected associations between risk factors and both CVD and death were also apparent., Conclusions: Data from the present sample, based on data linkage, show close agreement with South Korea-wide surveys (for risk factor prevalence) and the extant literature (for risk factor associations). These findings gives confidence in future results anticipated from this cohort study of east Asians - a group that has been traditionally under-researched., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Age-related differences in diabetes outcomes are important both for clinical and policy considerations. To clarify the basis of such differences, we investigated patterns of associations for age in relation to hospitalization and glycemic control and examined the role of other factors., Methods: 4471 patients with diabetes aged 40-79 years were drawn from a retrospectively retrieved National Health Insurance Cohort. Using logistic regression, risk factors measured over the two years (2007-2008) were examined for their associations with hospitalization and poor glycemic control during the last year (2009) of follow-up., Results: Compared to the middle-aged patients, older patients were more likely to have been hospitalized (Adjusted odds ratio (OR(adjusted)) = 1.97(95% CI = 1.28, 3.04) for the oldest group (ages 70-79) vs youngest group (ages 40-49)) but less likely to have poor glycemic control (OR(adjusted) = 0.45 (95% CI = 0.37, 0.56) for the oldest group vs youngest group). Older patients were also less likely to be obese but had more complications, longer duration of diabetes, lower continuity of care, and higher blood pressure and total cholesterol level. The pattern of associations for hospitalization and glycemic control was not uniform across the risk factors, sharing only a few common factors such as the duration of diabetes and blood pressure. In general, poor glycemic control was affected predominantly by metabolic management, while hospitalization was strongly related to functional status (i.e., number of complications) and care quality measures (i.e., continuity of care)., Conclusion: Hospitalization was higher among the older diabetic patients, despite better glycemic control. Factors were differently associated with the two diabetes-related outcomes, providing more comprehensive risk profiles for hospitalization. The co-existence of improved glycemic control and increased hospitalization among older diabetic patients suggests an extension of a geriatric evaluation to wider functional and comorbidity status.

Objective: The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score., Design: A prospective cohort study within a national insurance system., Setting: 18 health promotion centres nationwide between 1996 and 2001 in Korea., Participants: 268 315 Koreans between the ages of 30 and 74 years without CHD at baseline., Outcome Measure: Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI)., Results: The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3-6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort., Conclusions: The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Adiponectin is found to associate with diabetes in studies apart from cohort studies. This prospective cohort study is to evaluate the predictive role of adiponectin in diabetes among participants with impaired fasting glucose (IFG). A total of 42,845 participants who visited 7 health examination centers located in Seoul and Kyunggi province, South Korea, during 2004-2008 were first included. Of the 42,845 participants, 5,085 participants had IFG. IFG was categorized as stage 1 (fasting glucose 100-109 mg/dL) or stage 2 (110-125 mg/dL). The incidence rates of diabetes were followed up to December, 2011. Hazard ratios (HRs) and 95 % confidence intervals (CI) were performed by Cox proportional hazard model. Of the 5,085 participants, 652 participants developed diabetes during a mean follow-up of 4.4 years. Low adiponectin was associated with diabetes among men with stage 2 IFG (HR, 1.78; 95 %CI, 1.33-2.38) while it was associated with diabetes among women with stage 1 IFG (HR, 2.64; 95 %CI, 1.38-5.03) and stage 2 IFG (HR, 2.17; 95 %CI, 1.07-4.42). When combined men and women, the association between adiponectin and diabetes was statistically significant in stage 2 IFG with an increase of about 82 % (HR, 1.82; 95 %CI, 1.40-2.39) after adjusting for age, sex, body mass index, waist circumference, and fasting serum glucose. There was an interaction by sex and stage 1 IFG in the association between adiponectin and risk of diabetes (P < 0.001). Adiponectin was independently associated with diabetes among participants with IFG. This association was apparent in stage 2 IFG. Adiponectin may be used as a predictor of diabetes in patients having IFG.

Objective: To examine the validity and reliability of a new questionnaire for measuring depression in a South Korean population, and then to estimate the prevalence of depression in that country using this tool., Methods: In total, 742,600 individuals (123,725 women), aged 30-64 years at entry into the Korean Cancer Prevention Study, completed a depression symptom in 1992 (baseline enrollment) and again in 1994. We examined the concurrent validity of the depression questionnaire by relating data from it to known socio-demographic and behavioral correlates of depression; its predictive capacity by relating scores from the questionnaire to the occurrence of future hospitalization for depression; and the test-retest reliability by comparing scores from its administration in 1992 to those in 1994., Results: The prevalence of major depression was 7.5% in men and 10.0% in women. Factors significantly related to major depression were being younger (men), being female, not being married, of lower socioeconomic status, being a smoker, a heavy drinker, and not exercising regularly. Men (hazard ratio; 95% confidence interval: 2.0; 1.8, 2.2) and women (1.6; 1.3, 1.9) with questionnaire-ascertained depression experienced an elevated risk of hospitalization for the disorder during follow-up. The rates of agreement between responses to 1992 and 1994 surveys were 91.3% in men and 88.3% in women., Conclusions: These findings imply validity of the instrument and support its use in future studies directed at links of depression with somatic disease endpoints., Limitation: The questions do not have a specified time frame of reference., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women., Methods: A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used., Results: Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders., Conclusion: A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

Objective: Although diabetes increases the risk of cardiovascular disease (CVD) and mortality, the dose-response relationship between fasting glucose levels below those diagnostic of diabetes with cardiovascular events has not been well characterized., Research Design and Methods: A prospective cohort study of more than one million Koreans was conducted with a mean follow-up of 16 years. A total of 1,197,384 Korean adults with no specific medical conditions diagnosed were classified by baseline fasting serum glucose level. Associations of fasting glucose level with CVD incidence and mortality, stroke incidence and mortality, and all-cause mortality were analyzed using multivariate proportional hazards regression., Results: The relationships between fasting glucose levels and CVD risks generally followed J-shape curves, with lowest risk in the glucose range of 85-99 mg/dL. As fasting glucose levels increased to >100 mg/dL, risks for CVD, ischemic heart disease, myocardial infarction, and thrombotic stroke progressively increased, but risk for hemorrhagic stroke did not. Fasting glucose levels <70 mg/dL were associated with increased risk of all stroke (hazard ratio 1.06, 95% CI 1.01-1.11) in men and (hazard ratio 1.11, 1.05-1.17) in women., Conclusions: Both low glucose level and impaired fasting glucose should be considered as predictors of risk for stroke and coronary heart disease. The fasting glucose level associated with the lowest cardiovascular risk may be in a narrow range.

The regulations of the NO and PGE(2) productions are research topics of interest in the field of anti-inflammatory drug development. In the present study, 5,6,7-trimethoxy- and 5,6,7-trihydroxyflavones 3a-3g were synthesized from cinnamic acid derivatives. In particular, 4'-bromo-5,6,7-trimethoxyflavone (3b) most potently inhibited the productions of NO and PGE(2) in LPS-treated RAW 264.7 cells (IC(50)=14.22 ± 1.25 and 10.98 ± 6.25 μM, respectively), and these inhibitory effects were more potent than those of oroxylin A or baicalein. Consistent with these findings, 3b concentration-dependently reduced the LPS-induced expressions of iNOS and COX-2 at the protein and mRNA levels. In addition, the release of TNF-α, IL-6, and IL-1β and the mRNA expressions of these cytokines were reduced by 3b in a concentration-dependent manner. Furthermore, 3b attenuated the LPS-induced transcriptional activities of NF-κB and this was accompanied by parallel reductions in the degradation and phosphorylation of IκB-α, and consequently by a decrease in the nuclear translocation of the p65 subunit of NF-κB. Taken together, these results suggest that suppressions of the expressions of iNOS, COX-2, TNF-α, IL-6, and IL-1β via NF-κB inactivation are responsible for the anti-inflammatory effects of 3b., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A new hard x-ray beamline, 10B KIST-PAL beamline (BL10B), has been designed and constructed at the Pohang Light Source (PLS) in Korea. The beamline, operated by Pohang Accelerator Laboratory-Korean Institute of Science and Technology consortium, is dedicated to x-ray scattering (XRS) and x-ray absorption fine structure (XAFS) experiments. X rays with photon energies from 4.0 to 16.0 keV are delivered to the experimental station passing a collimating mirror, a fixed-exit double-crystal Si(111) monochromator, and a toroidal mirror. Basic experimental equipment for XAFS measurement, a high resolution diffractometry, an image plate detector system, and a hot stage have been prepared for the station. From our initial commissioning and performance testing of the beamline, it is observed that BL10B beamline can perform XRS and XAFS measurements successfully.

Background: Narcolepsy typically begins between adolescence and early adulthood causing severe neuropsychiatric impairments, but few prevalence studies are available on adolescent narcoleptics. In the present study, we investigated the prevalence of narcolepsy-cataplexy in adolescents., Methods: In total 20,407 students, aged 14-19 years, participated in this study. Ullanlinna Narcolepsy Scale (UNS) was applied to all subjects and those with a UNS score of > or =14 were contacted by phone for semi-structured interview. Subjects then suspected of having narcolepsy participated in a laboratory investigation, which included polysomnography and HLA typing, or were interviewed in detail by telephone., Results: Three subjects were finally diagnosed as narcolepsy with cataplexy and seven subjects might be diagnosed as narcolepsy without cataplexy. Among three narcoleptics with cataplexy, two subjects were HLA-DQB1*0602 and DRB1*1501 positive, but one subject had no test of HLA typing. The prevalence of narcolepsy with cataplexy in Korean adolescence was thus determined to be 0.015% (95% confidence interval = 0.0-0.0313%)., Conclusion: This epidemiologic study is the first of its type on adolescent narcolepsy to use the International Classification of Sleep Disorders, 2nd edition (ICSD-2) diagnostic criteria. Considering those cases with an onset after adolescence were not included, the prevalence of narcolepsy with cataplexy determined in the present study is comparable with that of other studies in adults.

Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-gamma secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4(+) memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.

General regulations and risk assessment regarding toxicants are single-compound oriented even though humans are exposed to multi-chemicals in the general environment. This study investigated the effects of different levels of N,N-dimethylformamide (DMF) and co-exposure levels of methyl ethyl ketone (MEK) and toluene (TOL) on two biomarkers of DMF exposure: non-metabolized urinary (U-)DMF and the DMF metabolite urinary N-methylformamide (NMF). Thirty-five workers were selected from a two-stage field investigation strategy and were classified into four groups based on DMF exposure and co-exposure levels. Breathing-zone air concentrations of DMF, MEK, and TOL as well as dermal DMF exposure were determined. Post-shift U-DMF and U-NMF levels were determined for each individual. U-DMF concentrations were significantly higher in high-DMF groups than in low-DMF groups, but U-NMF concentrations were significantly (P<0.05) lower in the high-DMF-high-co-exposure group than in the high-DMF-low-co-exposure group; there were no significant differences between two low-DMF groups. The ratio of U-NMF to U-DMF showed the biotransformation from DMF to NMF was significantly suppressed at high co-exposure (P<0.001) for high-DMF exposure groups, possibly because of competitive inhibition of CYP2E1, the responsible enzyme involved. Due to the ubiquity of MEK/TOL in DMF-exposed occupational settings, the biological exposure index for occupational DMF exposure should be re-evaluated at high co-exposure levels.

IL-23 is a heterodimeric cytokine consisting of p19 and the p40 subunit of IL-12. IL-23 has been shown to possess IL-12-like biological activities, but is different in its capacity to stimulate memory T cells in vitro. In this study, we investigated whether IL-23 could influence envelope protein 2 (E2)-specific cell-mediated immunity induced by immunization of hepatitis C virus E2 DNA. We found that IL-23 induced long-lasting Th1 and CTL immune responses to E2, which are much stronger than IL-12-mediated immune responses. Interestingly, IL-23N220L, an N-glycosylation mutant showing reduced expression of excess p40 without changing the level of IL-23, exhibited a higher ratio of IFN-gamma- to IL-4-producing CD4(+) T cell frequency than did wild-type IL-23, suggesting a negative regulatory effect of p40 on Th1-prone immune response induced by IL-23. These data suggest that IL-23, particularly IL-23N220L, would be an effective adjuvant of DNA vaccine for the induction of durable Ag-specific T cell immunity.

The envelope protein of hepatitis C virus (HCV) is composed of two membrane-associated glycoproteins, E1 and E2. To obtain HCV E2 protein as a secretory form at a high level, we constructed a recombinant chinese hamster ovary (CHO) cell line expressing a C-terminal truncated E2 (E2t) fused to human growth hormone (hGH), CHO/hGHE2t. The hGHE2t fusion protein was purified from the culture supernatant using anti-hGH mAb affinity chromatography at approximately 80% purity. The purified hGHE2t protein appeared to be assembled into oligomers linked by intermolecular disulfide bond(s) when density gradient centrifugation and SDS-polyacrylamide gel electrophoresis were employed. When the purified fusion protein was used for testing its ability to bind to antibodies specific for HCV by enzyme-linked immunosorbent assay, the protein was recognized by antibodies in sera from 90% of HCV-positive patients. Treatment of hGHE2t protein by beta-mercaptoethanol, but not by heat and SDS, significantly reduced its reactivity to the antibodies of patient sera, suggesting that intermolecular and/or intramolecular disulfide bonds are important for its ability to recognize its specific antibody and that the E2 protein contains discontinuous antigenic epitope(s).

Cyclic AMP-regulated gene expression is mediated by specific phosphoproteins (CREBs) which bind to cAMP-responsive elements of gene promoters. By analyzing the transactivation activities and phosphorylations in vivo of deletion and point mutated chimeric fusion proteins of the placental CREB-327, in which the DNA-binding domain is replaced by the heterologous binding-domain of the yeast transcription factor GAL4, we localized the cAMP-responsive and phosphorylated domain to a minimal-essential sequence module of 46 amino acids (residues 92-137). This serine-rich, multiply-phosphorylated sequence consists of at least three interdependent subdomains required for transcriptional activation. Although phosphorylation of serine-119 by cyclic AMP-dependent protein kinase A is necessary for transcriptional activation, such activation requires both a phosphorylated heptadecapeptide domain located ten residues amino terminal to the serine-119 and an eleven-residue domain carboxyl terminal to the serine-119. Deletion of these two domains does not impair phosphorylation of serine-119. Further, deletion of the carboxyl-terminal domain does not alter phosphorylation of the heptadecapeptide domain. We propose that akin to the phosphorylation-dependent activation of enzymes, the transcriptional transactivation functions of CREB-327 involve a phosphorylation-dependent allosteric conformational mechanism.

The expression of genes in response to cAMP is mediated by one or more trans-activator proteins, CREBs, that bind to cAMP-responsive enhancers (CREs) of the general motif 5'-TGACGTCA-3'. The carboxyl-terminal amino acid sequences of two isoforms of CREB, CREB-327 and CREB-341, deduced from the cDNAs consist of a positively charged (basic) region adjacent to a leucine zipper motif. Three peptides corresponding to the hypothetical DNA-binding and dimerization domains of CREB-327 were synthesized. A peptide that includes both the basic and leucine zipper domains binds to the CRE specifically. Moreover, this peptide readily forms CRE-binding heterodimers with full-length CREB both synthesized by in vitro cell-free translation and isolated from PC-12 cells, but did not heterodimerize with in vitro translated jun or fos. Two other peptides, either partially or totally lacking the basic region, but containing the intact leucine zipper domain, readily form dimers but do not bind to the CRE. We conclude that the carboxy-terminal basic and leucine zipper regions are necessary and sufficient for specific binding of CREB to the CRE as a homodimer. The leucine zipper domain is responsible for the dimerization, and the basic region confers binding specificity for the CRE. Heterodimerization of CREB-327 does not form heterodimers with jun or fos.

Clones carrying sequences expressed at altered abundance levels in dunce mutants were isolated by differentially screening a genomic library with cDNA probes representing the RNA population from dunce+ flies and the RNA population from dunce mutant flies. These mutants have an elevated cAMP content, so some isolates potentially contain cAMP responsive genes. Two classes of clones were isolated. One class contains genes expressed at a higher steady state abundance level in dunce mutants compared to dunce+ flies and the other contains genes expressed at a lower steady state level in the mutants. The recovery of clones from the differential screen demonstrates that in addition to altering normal behavior, fertility, and cAMP metabolism, dunce mutation confers an alteration in the level of expression of certain genes. The class of clones carrying sequences which are overexpressed in the mutants have been characterized. These clones carry a common repetitive sequence which codes for a 5.5 kb poly(A)+ RNA - the RNA species found to be overexpressed in the mutants. Restriction analysis and hybridization experiments show these repetitive sequences to be members of the copia family of transposable elements. Administration of pharmacological agents to normal flies to increase cAMP levels leads to an increased steady state level of copia RNA. Thus, copia RNA metabolism appears to be influenced by cAMP levels.