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Background Cross-national studies are an emerging research area in public health. Specifically, cross-national health comparisons are important for understanding the factors driving the success or failure of public health policies. Therefore, this study systematically analyzed studies that compared health status (physical health and cognition) of the older adults using national panel data for three East Asian countries—China, Japan, and Korea. Methods Google Scholar and PubMed were used for the literature search. The search strategy targeted papers published between 2005 and 2020, yielding a total of 2690 papers, of which seven were selected for the review. The Center for Evidence-Based Medicine (CEBM) criteria was used to assess study design quality. The risk of bias for non-randomized studies (RoBANS) tool, a quality assessment tool developed in Korea to evaluate non-randomized interventional studies, measured risk of bias. Results Of the seven included papers, two studies performed cognitive comparisons, four studies performed physical health comparisons, and one study compared both cognition and physical health. The studies selected for this study by CEBM criteria included four prospective cohort studies (Level 2B) and three expert opinions without explicit critical appraisal (Level 5). Risk of bias using the RoBANS tool found a risk of confounding variables in four out of seven papers. Finally, measurement items of cognitive and physical health differed across all three countries’ panel surveys. Conclusion These results suggest that in order to compare East Asian health policies according to the aging society, it is necessary to develop consistent cognitive and physical health evaluation tools in the future.

Summary: Background: Mammography is the current standard for breast cancer screening. This study aimed to develop an artificial intelligence (AI) algorithm for diagnosis of breast cancer in mammography, and explore whether it could benefit radiologists by improving accuracy of diagnosis. Methods: In this retrospective study, an AI algorithm was developed and validated with 170 230 mammography examinations collected from five institutions in South Korea, the USA, and the UK, including 36 468 cancer positive confirmed by biopsy, 59 544 benign confirmed by biopsy (8827 mammograms) or follow-up imaging (50 717 mammograms), and 74 218 normal. For the multicentre, observer-blinded, reader study, 320 mammograms (160 cancer positive, 64 benign, 96 normal) were independently obtained from two institutions. 14 radiologists participated as readers and assessed each mammogram in terms of likelihood of malignancy (LOM), location of malignancy, and necessity to recall the patient, first without and then with assistance of the AI algorithm. The performance of AI and radiologists was evaluated in terms of LOM-based area under the receiver operating characteristic curve (AUROC) and recall-based sensitivity and specificity. Findings: The AI standalone performance was AUROC 0·959 (95% CI 0·952–0·966) overall, and 0·970 (0·963–0·978) in the South Korea dataset, 0·953 (0·938–0·968) in the USA dataset, and 0·938 (0·918–0·958) in the UK dataset. In the reader study, the performance level of AI was 0·940 (0·915–0·965), significantly higher than that of the radiologists without AI assistance (0·810, 95% CI 0·770–0·850; p

AIMS: We evaluated the use and annual cost of complementary and alternative medicine (CAM) compared to conventional medicine in type 2 diabetes mellitus (DM) in the Korean population. METHODS: We analyzed the database of 2752 DM patients obtained from the Korean National Diabetes Program (KNDP). The cost data of conventional medicine starting 1-year before enrolment of the KNDP were obtained from the hospital electronic database. The cost data of CAM over the same period were obtained from questionnaires. RESULTS: Among the 2752 subjects, 677 patients (24.6%) used CAM, with the most common type being red ginseng and herbal medicine. Patients with a higher income, neuropathy, and self-monitoring of blood glucose (SMBG) were more likely to use CAM. Men, those with a higher education level and income, no cerebrovascular accident (CVA) history, and SMBG showed a relatively higher cost of CAM of total medical cost. The independent predictors for CAM were a higher income, the existence of diabetic neuropathy, no CVA history, and SMBG. CONCLUSIONS: Use and cost of CAM varied depending on income, accompanying complications and SMBG. To evaluate the total medical costs in DM patients, a comprehensive approach considering not only conventional cost but also CAM is required. [ABSTRACT FROM AUTHOR]

Purpose: This study has a purpose to investigate the side effects of three EGFR-TKIs targeted therapeutic agents (gefitinib, erlotinib, and afatinib) and all-cause mortality in patients with metastatic lung cancer., Methods: We performed a prospective cohort study. We selected all patients with newly diagnosed metastatic lung cancer between January and November 2019. Main exposure was daytime versus nighttime use of targeted EGFR TKIs. The study outcome was a symptom change using the mobile application, and all-cause mortality between January 2019 and March 2023., Results: Among the 87 study participants, 35 (40%) took their medication at night. Among the 87 study participants, 35 (40%) took their medication at night. At 6 weeks of treatment, acne (1.36; 95% confidence interval [CI] 1.09, 1.64; p for interaction = 0.04) and dry skin (1.35; 95% CI 1.09, 1.61, p for interaction = 0.01) in the day group showed a much increase from baseline compared to the night group. In contrast, the night group reported greater reductions in lung cancer-related symptoms from baseline compared to the day. During follow-up (median 43 months), the night group had a lower risk of all-cause death than the day group, especially in younger patients (adjusted hazard ratio = 0.34; 95% CI 0.13, 0.87)., Conclusions: The group taking EGFR-TKIs at night experienced fewer side effects and had longer overall survival compared to the day group. Clinicians should consider recommending that lung cancer patients take their once-daily oral anticancer drugs in the evening rather than the morning to improve treatment outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Although cross-sectional studies have reported the relationships among performance of activities of daily living (ADLs), income satisfaction, and health satisfaction, longitudinal associations in stroke survivors remain unclear., Objective: To examine the effects of ADL function and income satisfaction on health satisfaction over time in stroke survivors., Design: Retrospective longitudinal study designs with latent growth curve models (LGMs) to control for time-varying and time-invariant covariates., Setting: Community., Participants: A total of 198 stroke survivors., Outcomes and Measures: Self-reported ADL performance, income satisfaction, and health satisfaction., Results: The average age of participants was 70.68 yr (SD = 8.09; 107 men, 91 women). Each LGM showed that an increase in ADL score (standardized β = 0.116∼0.296, all ps < .05) and income satisfaction (standardized β = 0.513∼0.726, all ps < .001) positively predicted health satisfaction over time, even after controlling for time-varying annual income, demographics, and behavioral characteristics. The fit results of all LGMs were within the acceptable range: χ2(47) = 66.378, p = .0327; χ2(47) = 57.742, p = .1355; root-mean-square error of approximation, <0.08; comparative fit index and Tucker-Lewis index, >0.90; standardized root-mean-square residual, <0.05., Conclusions and Relevance: Because ADLs are significant modifiable health satisfaction factors, occupational therapy practitioners would need to focus more closely on ADL training in clinical settings. Furthermore, referring those clients to appropriate vocational rehabilitation to improve their income satisfaction would be necessary. Plain-Language Summary: This study recognizes the unique challenges and opportunities that arise when stroke survivors are preparing to return to their communities by emphasizing the significance of ADL training and income satisfaction during this stage of recovery. The study suggests that the therapeutic use of ADL training and income satisfaction could increase health satisfaction for stroke survivors. Therefore, comprehensive ADL training, as an occupational therapy intervention, could be crucial for stroke survivors who are preparing to return to their community from a clinical setting. Furthermore, connecting with vocational rehabilitation could also be important for improving income satisfaction for stroke survivors who are preparing to return to a community., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)

Hypoxia plays an essential role in the pathogenesis of various liver diseases, and albumin is one of the important biomarkers secreted by the liver. In this study, we developed an albumin monitoring system composed of hepatic hypoxia-on-a-chip and an albumin sensor to study liver function change due to hypoxia. In hepatic hypoxia-on-a-chip, we vertically stack an oxygen-scavenging channel on a liver on a chip with a thin gas-permeable membrane in the middle. This unique design of the hepatic hypoxia-on-a-chip can help to induce hypoxia quickly, attaining <5% within 10 min. An electrochemical albumin sensor was fabricated based on the covalent immobilization of antibodies on the Au electrode to monitor albumin secreting function on the hepatic hypoxia-on-a-chip. Standard albumin samples spiked in PBS, and culture media were measured by the electrochemical impedance spectroscopy using the fabricated immunosensor. The LOD was calculated to be 10 ag/mL in both cases. Using the electrochemical albumin sensor, we measured albumin secretion in normoxia and hypoxia in the chips. The albumin concentration decreased to 27% after 24 h in hypoxia compared to normoxia. This response was consistent with physiological studies. With technical refinements, the present albumin monitoring system can be a powerful tool in studying hepatic hypoxia with real-time liver function monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

(1) Background: The effectiveness of adjuvant chemotherapy in older patients with gastric cancer after D2-gastrectomy is unclear. This study investigated the efficacy of adjuvant chemotherapy in elderly patients with stage II/III gastric cancer. (2) Methods: A real-world population-based retrospective cohort of patients aged ≥65 with stage II/III gastric cancer (n = 2616; median age: 73.5; 12.2% aged >80 years) treated between 1 January 1997 and 31 December 2020 were included. All data was retrieved from the Hong Kong Hospital Authority Clinical Management System (CMS). Clinical characteristics of those patients with and without adjuvant chemotherapy treatment were balanced after propensity score matching (PSM). In total, 732 patients treated with adjuvant chemotherapy were matched with 732 patients treated with surgery alone. Hazard ratios (HRs) estimated via Cox proportional hazards regression models were used to compare the overall survival (OS) and cancer-specific survival (CSS) of the two patient groups. (3) Results: Adjuvant chemotherapy was associated with better OS (37 vs. 25 months; HR: 0.80; 95% CI: 0.75-0.84; p < 0.001) than surgery alone. The OS benefit was observed in both the 65-80 (44 vs. 27 months; HR: 0.79; 95% CI: 0.74-0.84; p < 0.001) and >80 (14 vs. 11 months; HR: 0.82; 95% CI: 0.71-0.96; p < 0.001) age groups. A better CSS was observed in patients who received adjuvant chemotherapy than those who only had surgery (5-year CSS: 64.1% vs. 61.1%, HR: 0.85; 95% CI: 0.79-0.93; p < 0.001). (4) Conclusions: adjuvant chemotherapy significantly improved OS and CSS in older patients with stage II/III gastric cancer.

Purpose: We aimed to identify factors influencing smoking cessation success among cancer patients registered in an inpatient smoking cessation program at a single cancer center., Materials and Methods: The electronic medical records of enrolled patients with solid cancer were retrospectively reviewed. We evaluated factors associated with 6-month smoking cessation., Results: A total of 458 patients with cancer were included in this study. Their mean age was 62.9±10.3 years, and 56.3% of the participants had lung cancer. 193 (42.1%) had not yet begun their main treatment. The mean number of counseling sessions for the participants was 8.4±3.5, and 46 (10.0%) patients were prescribed smoking cessation medications. The 6-month smoking cessation success rate was 48.0%. Multivariate analysis showed that younger age (<65 years), cohabited status, early stage, and the number of counseling sessions were statistically significant factors affecting 6-month smoking cessation success ( p <0.05). Initiation of a cessation program before cancer treatment was significantly associated with cessation success (odds ratio, 1.66; 95% confidence interval, 1.02-2.70; p =0.040)., Conclusion: Smoking cessation intervention must be considered when establishing a treatment plan immediately after a cancer diagnosis among smokers., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Whey protein (WP) in milk shows physiologically active functions such as cholesterol control and immune system strengthening. In this study, we performed hydrolysis and peptide polarity fractionation to enhance the efficacy and diversity of its physiological activities, using the digesting enzyme, pancreatin. Our results indicate that hydrolysis significantly increased the cell proliferation of the WP fractions, with the lower-polarity fractions showing greater efficacy in this regard. Our results indicate that hydrolysis significantly increases cell proliferation of the WP fractions. Additionally, we confirmed differences in the antioxidant activity of the WP fractions as a function of polarity was confirmed via scavenging 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay in vitro . WP itself did not show anti-inflammatory efficacy. However, all the hydrolyzed fractions downregulated the mRNA expression levels of inflammatory cytokines in all treated cell lines and, based on a senescence-associated (SA)-β-galactosidase assay, the fraction with the lowest polarity (F6) inhibited cellular senescence to the greatest extent. Furthermore, we identified the peptide sequences with various physiological activities from whey protein hydrolysates through mass spectrometry. Taken together, our results indicate that the fractionation of WP via hydrolysis generates novel functions including promoting cellular cell proliferation, anti-inflammatory effects, and enhancing antioxidant and anti-cellular senescence., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Lentilactobacillus buchneri isolated from Korean fermented plant foods produces β-glucosidase, which can hydrolyze ginsenoside Rb1 from Panax ginseng to yield ginsenoside Rd. The aim of this study was to determine the mechanisms underlying the extracellular β-glucosidase activity obtained from Lentilactobacillus buchneri URN103L. Among the 17 types of lactic acid bacteria showing positive β-glucosidase activity in the esculin iron agar test, only URN103L was found to exhibit high hydrolytic activity on ginsenoside Rb1. The strain showed 99% homology with Lentilactobacillus buchneri NRRLB 30929, whereby it was named Lentilactobacillus buchneri URN103L. Supernatants of selected cultures with β-glucosidase activity were examined for hydrolysis of the major ginsenoside Rb1 at 40 °C, pH 5.0. Furthermore, the β-glucosidase activity of this strain showed a distinct ability to hydrolyze major ginsenoside Rb1 into minor ginsenosides Rd and Rg3. Lentilactobacillus buchneri URN103L showed higher leucine arylamidase, valine arylamidase, α-galactosidass, β-galactosidase, and β-glucosidase activities than any other strain. We conclude that β-glucosidase from Lentilactobacillus buchneri URN103L can effectively hydrolyze ginsenoside Rb1 into Rd and Rg3. The converted ginsenoside can be used in functional foods, yogurts, beverage products, cosmetics, and other health products.

NAD(H)/NADP(H)-dependent aldehyde/alcohol oxidoreductase (AAOR) participates in a wide range of physiologically important cellular processes by reducing aldehydes or oxidizing alcohols. Among AAOR substrates, furan aldehyde is highly toxic to microorganisms. To counteract the toxic effect of furan aldehyde, some bacteria have evolved AAOR that converts furan aldehyde into a less toxic alcohol. Based on biochemical and structural analyses, we identified Bacillus subtilis YugJ as an atypical AAOR that reduces furan aldehyde. YugJ displayed high substrate specificity toward 5-hydroxymethylfurfural (HMF), a furan aldehyde, in an NADPH- and Ni 2+ -dependent manner. YugJ folds into a two-domain structure consisting of a Rossmann-like domain and an α-helical domain. YugJ interacts with NADP and Ni 2+ using the interdomain cleft of YugJ. A comparative analysis of three YugJ structures indicated that NADP(H) binding plays a key role in modulating the interdomain dynamics of YugJ. Noticeably, a nitrate ion was found in proximity to the nicotinamide ring of NADP in the YugJ structure, and the HMF-reducing activity of YugJ was inhibited by nitrate, providing insights into the substrate-binding mode of YugJ. These findings contribute to the characterization of the YugJ-mediated furan aldehyde reduction mechanism and to the rational design of improved furan aldehyde reductases for the biofuel industry.

We propose a biomedical sensor system for continuous monitoring of glucose concentration. Despite recent advances in implantable biomedical devices, mm sized devices have yet to be developed due to the power limitation of the device in a tissue. We here present a mm sized wireless system with backscattered frequency-modulation communication that enables a low-power operation to read the glucose level from a fluorescent hydrogel sensor. The configuration of the reader structure is optimized for an efficient wireless power transfer and data communication, miniaturizing the entire implantable device to 3 × 6 mm 2 size. The operation distance between the reader and the implantable device reaches 2 mm with a transmission power of 33 dBm. We demonstrate that the frequency of backscattered signals changes according to the light intensity of the fluorescent glucose sensor. We envision that the present wireless interface can be applied to other fluorescence-based biosensors to make them highly comfortable, biocompatible, and stable within a body.

Resonant optical excitation of certain molecular vibrations in κ-(BEDT-TTF)&#95;{2}Cu[N(CN)&#95;{2}]Br has been shown to induce transient superconductinglike optical properties at temperatures far above equilibrium T&#95;{c}. Here, we report experiments across the bandwidth-tuned phase diagram of this class of materials, and study the Mott insulator κ-(BEDT-TTF)&#95;{2}Cu[N(CN)&#95;{2}]Cl and the metallic compound κ-(BEDT-TTF)&#95;{2}Cu(NCS)&#95;{2}. We find nonequilibrium photoinduced superconductivity only in κ-(BEDT-TTF)&#95;{2}Cu[N(CN)&#95;{2}]Br, indicating that the proximity to the Mott insulating phase and possibly the presence of preexisting superconducting fluctuations are prerequisites for this effect.

Sarcopenia is a disease characterized by the loss of muscle mass and function that occurs mainly in older adults. The present study was designed to investigate the hypothesis that water extract of Lycium chinense (WELC) would improve muscle function and promote myogenesis for sarcopenia. We investigated the effect of water extracts of L .  chinense on muscular endurance function and myogenesis to examine its efficacy in sarcopenia. Intake of WELC-containing cheese enhanced the muscular endurance function of mice in treadmill endurance tests. In addition, the cross-sectional areas of muscle fibers in the gastrocnemius muscle of L .  chinense -fed mice were greater than that of control mice. Furthermore, WELC and its key component marker substance betaine promoted myogenesis of myoblasts by increasing the expression of the myogenic protein myosin heavy chain 3 (Myh3) and myotube formation. Taken together, our results suggest that L .  chinense may potentially be useful in the development of preventive and therapeutic agents for sarcopenia, as well as in providing basic knowledge on myogenesis and muscular functions., Competing Interests: The authors have declared no conflicts of interest., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Objective: The TYR (Tyrosinase) and MC1R (Melanocortin 1 receptor) genes are recognized as important genes involved in plumage pigmentation in Korean native chickens. Specifically, most color patterns in chicken result from differential expression of the TYR gene. In this study, the co-segregation of the pigmentation and sequence of the TYR and MC1R genes was investigated through intercrosses between red (R1q1), red with black and black plumage color types of native Korean chickens., Materials and Methods: Using DNA, RNA, and tissue by plumage color of each Korean native chickens, the role of major genes in pigmentation of pheomelanin was evaluated. Reverse transcription polymerase chain reaction, sequencing, western blot, and immunohistochemical were performed to determine the effect of TYR and MC1R genes on plumage pigmentation in Korean native chickens., Results: The KCO line (Korean chicken Ogol: Black-line) with an EEC &#95; genotype exhibited black feathers, whereas red and red mixed with black chicken with EeC genotype exhibited white feathers. There were notable differences between the base sequences of MC1R and TYR in three Korean chicken breeds, with the highest variation in TYR . Perhaps this is the key characteristics of Korean chicken. Further, we analyzed the expression patterns of MC1R and TYR genes in each type of Korea native chicken and observed that TYR expression was high in feather follicle (R1q2) of KCO tissue. However, native red (Korean chicken red) and native red with black (Korean chicken red dark) chickens have increased TYR expression in the tissue. However, the expression of MC1R was much different from that of TYR ., Conclusion: In this study, our results suggest that the differences in position and TYR expression levels exert more influence on plumage pigmentation in native Korean chicken breeds than changes in MC1R expression levels., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Cheese contains various beneficial nutrients, including calcium and whey protein, as well as large amounts of saturated fatty acids. Thus, intake of cheese increases the production of low-density lipoprotein-cholesterol (LDL-C), a well-defined risk factor for cardiovascular disease. Therefore, identification of natural products that inhibit LDL-C production following cheese intake and verification of the efficacy of such products in animal models are essential. Here, we evaluated the effects of Allium hookeri , a well-known traditional herbal remedy, on metabolism and thermogenesis in mice consuming a cheese-containing diet. Intake of A. hookeri extracts significantly blocked increases in body weight and fat mass caused by intake of Gouda cheese in mice. Additionally, increases in blood triglyceride levels following intake of Gouda cheese were alleviated by A. hookeri . Moreover, intake of Gouda cheese enhanced thermogenesis efficiency. Thus, A. hookeri may have applications as an important additive for reducing the risk of metabolic disease resulting from cheese consumption., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Dekkera anomala YAE-1 strain separated from "airag" (Mongolian fermented mare's milk) produces β-glucosidase, which can convert ginsenoside Rb 1 from Panax ginseng. Ginseng-derived bioactive components such as ginsenoside Rb 1 have various immunological and anticancer activities. Airag was collected from five different mare milk farms located near Ulaanbaatar, Mongolia. YAE-1 strains were isolated from airag to examine the hydrolytic activities of β-glucosidase on Korean Panax ginseng using an API ZYM kit. Supernatants of selected cultures having β-glucosidase activity were examined for hydrolysis of the major ginsenoside Rb 1 at 40°C, pH 5.0. The YAE-1 strain was found to be nearly identical at 99.9% homology with Dekkera anomala DB-7B, and was thus named Dekkera anomala YAE-1. This strain exerted higher β-glucosidase activity than other enzymes. Reaction mixtures from Dekkera anomala YAE-1 showed great capacity for converting ginsenoside Rb 1 to ginsenoside Rd. The β-glucosidase produced by Dekkera anomala YAE-1 was able to hydrolyze ginsenoside Rb 1 and convert it to Rd during fermentation of the ginseng. The amount of ginsenoside Rd was highly increased from 0 to 1.404 mg/ml in fermented 20% ginseng root at 7 days.

Methods: This cross-sectional study based on the Korean National Diabetes Program 2 registry used its baseline clinical data collected from seven participating university hospitals in Korea. Patients with no significant changes in their oral hypoglycemic agents and no diabetes-related complications within the year prior to participation were enrolled. Patients' clinical characteristics according to metformin use were analyzed., Results: Among 858 subjects included in the analyses, 706 were metformin users and 152 were nonmetformin users. Metformin users were significantly younger and had higher and glycated hemoglobin with significantly lower rates of accompanying microvascular complications such as retinopathy, cataracts, overt proteinuria, renal insufficiency, and peripheral neuropathy than nonusers. Meanwhile, there was a significantly lower prevalence of malignancy and depression among metformin users. These associations remained significant in multivariate analyses. The prevalence rate of macrovascular complications was not significantly different between the two groups., Conclusions: There were significant differences with respect to clinical characteristics and comorbidity prevalence according to metformin use among Korean type 2 diabetes patients. Long-term follow-up of these patients is necessary to observe how this difference will affect clinical outcomes for these patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Sang Ouk Chin et al.)

Background: To evaluate corneal epithelial thickness change during medical treatment for eyes with myopic regression after femtosecond laser-assisted in situ keratomileusis (FS-LASIK)., Methods: This study included 84 eyes of 54 subjects diagnosed with myopic regression after FS-LASIK and treated using topical steroid and anti-glaucoma drugs. Corneal epithelial thickness was measured using Fourier-domain optical coherence tomography before and after treatment. Subjects were divided into three groups based on their corneal epithelial thickness at the time of myopic regression and regression analyses were used to investigate the association between corneal epithelial thickness, visual acuity, and refraction. Logistic regression and receiver operating characteristic (ROC) curve analysis was performed to determine whether corneal epithelial thickness could predict the success of treatment, improvements of ≥ two lines in uncorrected distance visual acuity and ≥ 0.5 diopter in refraction or K., Results: Corneal epithelial thickness decreased with greater change in the center as myopic regression subsided during medical treatment. Subgroup with the thickest epithelium (≥ 62 μm) showed a higher success rate and greater changes in refraction and vision. Reduced magnitude of corneal epithelial thickness showed significant correlations with changes of K and refractive error (all P < 0.001). Corneal epithelial thickness was a significant factor for the success of treatment and ROC curve showed that corneal epithelial thickness > 60.50 μm had 81.5% sensitivity and 84.2% specificity for the success of medical treatment., Conclusion: Corneal epithelial thickness decreases proportionally with the magnitude of improvement of myopic regression during treatment with steroid and anti-glaucoma drugs in post-LASIK eyes with myopic regression.

Background: Voriconazole, a triazole antifungal agent exhibits broad-spectrum antifungal activity. It is used to treat severe, invasive fungal infections, including invasive aspergillosis and candidemia. The aim of this study was to assess the pharmacokinetic equivalence of a test formulation (Vorico® Injection) and reference formulation (Vfend® IV) of voriconazole., Materials and Methods: This was a randomized, open-label, single-dose, three-group, two-treatment, two-sequence, two-period, crossover phase I trial with 7-day washout periods (ClinicalTrials.gov identifier NCT02631954). Twenty-four healthy Korean male subjects were recruited. In each group, eight subjects were randomized in a 1:1 manner to receive a single dose of 200 mg test or reference formulation intravenously over 1.5 h. Blood samples were collected over 24 h post-dose, and plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a non-compartmental analysis, and safety was evaluated., Results: Twenty-three subjects completed the study. The geometric mean ratio (90% confidence interval) of the test formulation to reference formulation was 0.9570 (0.8178 - 1.1199) for the maximum plasma concentration (C max ) and 1.0720 (1.0262 - 1.1198) for the area under the concentration-time curve from dosing to the last quantifiable concentration (AUC last ). The mean plasma concentration-time profiles, pharmacokinetic parameters, and safety were comparable between the two formulations., Conclusion: Equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence and similar safety profiles were observed for both test and reference formulations of voriconazole., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Purpose: Central retinal artery occlusion (CRAO) is an ophthalmic emergency with poor prognosis, despite diligent conventional treatment. According to the clinical recommendations of the Undersea and Hyperbaric Medical Society, hyperbaric oxygen (HBO2) is a potentially beneficial treatment; however, the benefit of adjunctive HBO2 in patients with CRAO in Korea remains unclear. The present study aimed to evaluate the effect of adjunctive HBO2 in patients with CRAO., Methods: This registry-based observational study included adult patients who presented to the emergency department or ophthalmology outpatient department within 24 hours of the onset of CRAO symptoms. Data of patients from October 2016 to February 2019 were analyzed. The patients were categorized into two groups according to the use of adjunctive HBO2: no HBO2 and HBO2., Result: During the study period, 34 consecutive patients were enrolled, of which 19 were included in the study. In the total cohort, 10 patients (52.6%) were treated with adjunctive HBO2. There were no statistically significant differences in terms of age, sex, comorbidities, duration from symptoms onset to hospital visit, presence of the cilioretinal artery, and use of anterior chamber paracentesis between the two groups. The HBO2 group showed significantly higher change in best-corrected visual acuity than the no HBO2 group (p=0.043)., Conclusion: Patients with CRAO in the HBO2 group showed significantly greater visual improvement than those in the no-HBO2 group. Clinicians should consider adjunctive HBO2 in the treatment approach in patients with CRAO who visit the hospital within 24 hours of symptoms onset., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Studies on the discovery and function of antioxidants are consistently being performed because oxidative stress can cause various diseases. Many compounds and natural products have antioxidant activity in vitro; however, it is often difficult to reproduce their effects in vivo. Additionally, methods to measure antioxidant activities in cells are also scarce. Here, we investigated the antioxidant activity of milk proteins by observing the formation of arsenite-induced stress granules as a tool to evaluate antioxidant activity in cells. Milk proteins not only decreased the formation of stress granules in several cell types but also scavenged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cations in vitro. In addition, milk proteins inhibited cellular senescence based on an SA-β-galactosidase assay, and increased differentiation to myotubes from myoblasts isolated from the skeletal muscles of mouse pups. Taken together, our results demonstrate that milk proteins have an antiaging effect, especially prevention of skeletal muscle loss, through their antioxidant activities. PRACTICAL APPLICATION: Our results provide that antioxidant effects of milk proteins containing α-caseins, β-caseins, and β-lactoglobulin can mitigate aging-related damage induced by oxidative stress through showing inhibition of cellular senescence and increase of differentiation and maturation of myoblast. Therefore, we suggest that milk proteins could be potent health supplements to prevent aging-associated diseases, especially sarcopenia., (© 2019 Institute of Food Technologists®.)

Objective: The aim of this study was to investigate the effects of omega-3 fatty acids added to statin monotherapy in Korean patients with type 2 diabetes who have persistent hypertriglyceridemia despite statin therapy., Methods: This study was a randomized controlled trial conducted in 4 clinical sites between February 2009 and February 2011. The inclusion criteria were patients with type 2 diabetes who had received ≥6 weeks of statin therapy and had fasting triglyceride (TG) levels ≥1.7mmol/L and low-density lipoprotein (LDL) cholesterol levels <2.6 mmol/L. The study regimen consisted of 16 weeks of randomized treatment with omega-3 fatty acids (4 g/day) plus a statin (n=26) or statin only (n=30). The primary endpoint was the change from baseline to final visit in mean TG level., Results: A total of 56 participants were analyzed. At week 16, the change in the TG level in the combination therapy group differed significantly from the change in the statin monotherapy group (-34.8% vs. -15.2%, p =0.0176). Treatment with omega-3 fatty acids plus a statin was also associated with a significant decrease in non-high-density lipoprotein cholesterol compared with baseline, but the difference was not significant compared with the statin monotherapy group (-8.0% vs. -2.5%, p =0.165). The changes in LDL cholesterol and HbA1c levels did not differ significantly between groups. The study medications were well tolerated, and adverse events were comparable between two groups., Conclusion: Adding omega-3 fatty acids to statin treatment reduced TG levels more effectively than statin monotherapy without undesirable effects in Korean type 2 diabetic patients who had hypertriglyceridemia despite well-controlled LDL cholesterol on stable statin therapy., Trial Registration: ClinicalTrials.gov Identifier: NCT02305355., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare. The funding source had no role in the collection of the data or in the decision to submit the manuscript for publication. Jang Won Son is an editor of Journal of Lipid and Atherosclerosis; however, he was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (Copyright © 2019 The Korean Society of Lipid and Atherosclerosis.)

Background: CT-P16 is a candidate biosimilar of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor that is used in the treatment of a range of advanced solid cancers., Objective: The objective of this study was to demonstrate the pharmacokinetic equivalence of CT-P16 and European Union (EU)-approved bevacizumab (EU-bevacizumab) and US-licensed bevacizumab (US-bevacizumab) reference products., Methods: In this double-blind, parallel-group phase I trial (ClinicalTrials.gov identifier NCT03247673), healthy adult males were randomized (1:1:1) to receive a single dose of CT-P16 5 mg/kg, EU-bevacizumab 5 mg/kg, or US-bevacizumab 5 mg/kg. Primary study endpoints were area under the concentration-time curve (AUC) from time zero to infinity (AUC ∞ ), AUC from time zero to the last quantifiable concentration (AUC last ), and maximum serum concentration (C max ). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean (GM) ratios of the AUC ∞ , AUC last , and C max were within the predefined bioequivalence margin of 80-125%. Safety and immunogenicity were also evaluated., Results: A total of 144 subjects were randomized: 47 to CT-P16, 49 to EU-bevacizumab, and 48 to US-bevacizumab. The 90% CIs for the GM ratios of AUC ∞ , AUC last , and C max for CT-P16/EU-bevacizumab, CT-P16/US-bevacizumab, and EU-bevacizumab/US-bevacizumab comparisons were all within the bioequivalence margin. Mean serum concentration-time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across all three treatment groups., Conclusion: CT-P16 demonstrated pharmacokinetic equivalence to EU-bevacizumab and US-bevacizumab. Safety and immunogenicity profiles were similar for CT-P16, EU-bevacizumab, and US-bevacizumab. These data support the further clinical evaluation of CT-P16 as a bevacizumab biosimilar., Clinical Trials Registration: NCT03247673.

Prediabetic subjects represent a vulnerable population, requiring special care to reduce the risk of diabetes onset. We developed and validated a diabetes risk score for prediabetic subjects using the Korea National Diabetes Program (KNDP) cohort. Subjects included in the multicenter and prospective cohort (n = 1162) had high diabetes risk at baseline (2005) and were followed until 2012. Survival analysis was performed to analyze the prospective cohort over time, and the bootstrap method was used to validate our model. We confirmed our findings in an external cohort. A diabetes risk score was calculated and the cut-off defined using a receiver operating characteristic curve. Age, body mass index, total cholesterol, and family history of diabetes were associated with diabetes. The model performed well after correction for optimism (C adj  = 0.735). A risk score was defined with a cut-off of ≥5 that maximized sensitivity (72%) and specificity (62%), with an area under the curve of 0.73. Prediabetic subjects with a family history of diabetes had a higher probability of diabetes (risk score = 5) irrespective of other variables; this result was confirmed in the external cohort. Hence, prediabetic subjects with a family history of diabetes have a higher probability of developing diabetes, regardless of other clinical factors.

Objective: This study aims to explore whether homeobox A11 antisense RNA (HOXA11-AS) could regulate inflammation induced by diabetic arteriosclerosis (DAA) via PI3K/AKT pathway., Patients and Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect expressions of HOXA11-AS and proinflammatory genes in carotid endarterectomy samples of symptomatic and asymptomatic atherosclerosis (AS) patients, diabetes mellitus (DM), and non-DM patients. The above-mentioned genes in DM animal model and non-DM animal model were also detected. We detected the expression of HOXA11-AS in vascular smooth muscle cells (VSMCs) treated with platelet-derived growth factor (PDGF) or PDGF inhibitor imatinib, respectively. Subsequently, we applied cell transfection technology to interfere with the expression of HOXA11-AS in VSMCs. In vascular endothelial cells (VECs) and VSMCs, we detected the effect of HOXA11-AS on the expressions of genes related to the proliferation, migration, and cell cycle. Then, VSMCs were treated with tumor necrosis factor-α (TNF-α), and the expression of HOXA11-AS was examined in VSMCs. The effect of HOXA11-AS on TNF-α-induced inflammation in VSMCs was detected as well. Finally, we analyzed the effect of HOXA11-AS on PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs., Results: HOXA11-AS expression was markedly increased in carotid endarterectomy specimens of symptomatic AS patients compared to that of asymptomatic AS patients. Expression levels of HOXA11-AS and pro-inflammatory genes were significantly elevated in carotid endarterectomy specimens of DM patients. Similarly, HOXA11-AS expression was also significantly increased in carotid arteries of DM mice compared with that of non-DM mice. PDGF could upregulate HOXA11-AS expression in VSMCs, which was reversed by PDGF inhibitor imatinib. HOXA11-AS knockdown could reduce the expressions of the proliferation-associated gene (PCNA) and the cycle-related genes (p21, p53), and also inhibited the proliferation and migration of VSMCs induced by PDGF. HOXA11-AS was upregulated by TNF-α. HOXA11-AS knockdown remarkably downregulated expressions of inflammation-related genes in VSMCs induced by TNF-α. In VECs, low expression of HOXA11-AS can inhibit the expression of TNF-α-induced pro-inflammatory genes and PDGF-induced vascular inflammation-related genes. Low expression of HOXA11-AS inhibited PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs., Conclusions: HOXA11-AS may participate in DAA by activating the PI3K/AKT pathway to regulate inflammation in VSMCs and VECs.

Background: The aim of the study was to assess the impact of socioeconomic status (SES) on health behaviors, metabolic control, and chronic complications in people with type 2 diabetes mellitus (T2DM) from South Korea, a country with universal health insurance coverage and that has experienced rapid economic and social transition., Methods: A total of 3,294 Korean men and women with T2DM aged 30 to 65 years, participating in the Korean National Diabetes Program (KNDP) cohort who reported their SES and had baseline clinical evaluation were included in the current cross-sectional analysis. SES included the level of education and monthly household income., Results: Lower education level and lower income level were closely related, and both were associated with older age in men and women. Women and men with lower income and education level had higher carbohydrate and lower fat intake. After adjustment for possible confounding factors, higher education in men significantly lowered the odds of having uncontrolled hyperglycemia (glycosylated hemoglobin ≥7.5%) (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.43 to 0.91 for highest education; P (trend)=0.048), while higher household income in men significantly lowered the odds of having diabetic retinopathy (OR, 0.59; 95% CI, 0.37 to 0.95 for highest income level; P (trend)=0.048). In women, lower income was associated with a higher stress level., Conclusion: Men with lower SES had higher odds of having diabetic retinopathy and uncontrolled hyperglycemia, showing the need to improve care targeted to this population., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018 Korean Diabetes Association.)

Aim: To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long-term glycaemic control and the preservation of β-cell function in people with type 2 diabetes mellitus (T2DM)., Methods: Newly diagnosed drug-naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow-up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti-glutamic acid decarboxylase autoantibody-positive., Results: Both intensive treatment methods were effective for short-term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow-up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well-controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow-up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug-free glycaemic remission compared with the COAD method (P = .015)., Conclusions: The findings indicate that outpatient clinic-based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in β-cell function and glycaemic control over the long term, without serious adverse events., (© 2017 John Wiley & Sons Ltd.)

The original version of this Article contained an error in the spelling of the author Benjamin H. Williams, which was incorrectly given as Benjamin H. Willams. This has now been corrected in both the PDF and HTML versions of the Article.

The epidemiological literature suggests that insulin resistance, hyperinsulinemia, and increased levels of insulin-like growth factors place patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The association between cancer incidence and the use of antidiabetic medications in patients with T2DM has been recently examined. There have been conflicting reports regarding an association between metformin and cancer risk. The aim of this study was to investigate the relationship between metformin use and the incidence of cancer in Koreans with T2DM.Data from The Korean National Diabetes Program (KNDP, 2006-2014), a nationwide, large-scale, prospective, multicenter cohort study in Korea, were used to study patients with T2DM. Patients ≥30 years old whose complete medical records were available were included in this study. Patients with a history of any cancer on KNDP registration or those who had been diagnosed with any type of cancer within 1 year of metformin use were excluded. Survival curves with respect to the incidence of cancer were plotted using the Kaplan-Meier method. Hazard ratios and 95% confidence intervals for cancer were estimated in a Cox proportional hazards regression analysis.During a mean 5.8 years of follow-up, 164 of the 1918 study patients (335 metformin nonusers and 1583 metformin users) developed cancer. The incidence per 1000 person-years was 21.8 in metformin nonusers and 13.2 in metformin users. Metformin users had a reduced risk of cancer, even after adjustment for demographic characteristics, metabolic parameters, diabetic complications, and other antidiabetic medications (hazard ratio 0.513, 95% confidence interval 0.318-0.826, P = .0060). Subgroup analysis of metformin users showed a reduced risk of cancer in males, patients < 65 years of age, patients with a T2DM duration < 5 years, nonobese patients, nonsmokers, and good glycemic control group.This large-scale, prospective, multicenter cohort study demonstrated an association between metformin use and reduced cancer risk in patients with T2DM.

To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA). However, ADMA showed a higher association with adolescent obesity (P < 0.001) and adult diabetes (P = 0.007) and decreased after obesity intervention program. Functional studies in cellular and mouse models demonstrated that an accumulation of ADMA is associated with the regulation of obesity-induced insulin resistance in skeletal muscle. ADMA treatment inhibited dimethylarginine-dimethylaminohydrolase (DDAH) activity and mRNA expression in insulin resistance muscle cell. Moreover, the treatment led to decrease of phosphorylation of insulin receptor (IR), AKT, and GLUT4 but increase of protein-tyrosine phosphatase 1B (PTP1B). Accordingly, increased ADMA significantly inhibited glucose uptake in myotube cell. We suggest that accumulation of ADMA is associated with modulation of insulin signaling and insulin resistance. ADMA might expand the possibilities of new therapeutic target for functional and clinical implications in the control of energy and metabolic homeostasis in humans.

Topological insulators exhibit a metallic surface state in which the directions of the carriers' momentum and spin are locked together. This characteristic property, which lies at the heart of proposed applications of topological insulators, protects carriers in the surface state from back-scattering unless the scattering centres are time-reversal symmetry breaking (i.e. magnetic). Here, we introduce a method of probing the effect of magnetic scattering by decorating the surface of topological insulators with molecules, whose magnetic degrees of freedom can be engineered independently of their electrostatic structure. We show that this approach allows us to separate the effects of magnetic and non-magnetic scattering in the perturbative limit. We thereby confirm that the low-temperature conductivity of SmB 6 is dominated by a surface state and that the momentum of quasiparticles in this state is particularly sensitive to magnetic scatterers, as expected in a topological insulator.

Analyses using a nationally representative cohort have revealed that high fatty liver index (FLI) is associated with low bone mineral density (BMD) regardless of insulin resistance in men, thereby supporting the deteriorated bone metabolism in nonalcoholic fatty liver disease (NAFLD)., Introduction: NAFLD is linked to deteriorated bone health. We investigated the association of FLI, a scoring model for NAFLD, with BMD., Methods: This was a population-based, cross-sectional study from the Korea National Health and Nutrition Examination Surveys including 4264 Koreans (1908 men and 2356 women). FLI was calculated using body mass index, waist circumference, serum triglyceride, and gamma-glutamyltranspeptidase level. Insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. BMD was measured using dual-energy X-ray absorptiometry at the lumbar spine, total hip, femoral neck, and whole body., Results: Men had a higher FLI than women, while the HOMA-IR index was similar between men and women. The significant association between FLI and BMD was observed only in men, but not in women. FLI was negatively correlated with total hip, femoral neck, and whole body BMD in men after adjusting for all potential confounders, including HOMA-IR (P < 0.001 to 0.010). Lumbar spine, total hip, femoral neck, and whole body BMD in men showed a decreasing trend as the FLI tertile increased after adjusting for all potential confounders, including HOMA-IR (P for trends < 0.001 to 0.034). In men aged 50 years or older, odds ratios for combined osteopenia and osteoporosis increased across increasing FLI tertiles after adjusting for confounders (P for trends < 0.011 to 0.029)., Conclusion: NAFLD is associated with low bone density regardless of insulin resistance in men. These findings suggest an undiscovered direct link between liver and bone that increases the risk of osteoporosis in men with NAFLD.

Aim: Diabetes mellitus (DM) patients are susceptible to foot injury or foot diseases such as diabetic foot and peripheral arterial disease. Although these conditions are considered important, few studies have investigated them in detail. Therefore, we investigated the epidemiology of diabetic foot complications (DFC) with respect to the effects on the public healthcare system., Methods: We evaluated the incidence, clinical characteristics, health service utilization frequency and medical expenses of DFC in type 2 DM patients in the Korea National Diabetes Program (KNDP), the largest multi-center, prospective cohort in Korea (n=4405). To determine precise outcomes, we used national representative databases, including claims data from the Health Insurance Review & Assessment Service of Korea., Results: During a median follow-up period of 3.30years, 528 patients (12.0%) were newly diagnosed with DFC at an incidence rate of 43.02 cases per 1000 person-years. The patients with DFC were significantly older than patients without DFC, but other clinical characteristics were similar between the two groups. The patients with DFC had more hospital visits (p<0.001), longer duration of hospitalization (p<0.001), and increased expenses (p<0.001) compared to patients without DFC. After multiple adjustments, the differences in number of hospital visits and medical expenses were consistent. In a before and after comparison within the DFC group, all three variables increased significantly after the onset of DFC (p<0.001)., Conclusions: DFC were significantly associated with poor clinical outcomes and caused a substantial burden to the national healthcare system in Korea. Therefore, intervention to prevent DFC is important., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study was conducted to isolate and characterize Paenibacillus sp. MBT213 possessing β-glucosidase activity from raw milk, and examine the enzymatic capacity on the hydrolysis of a major ginsenoside (Rb 1 ). Strain MBT213 was found to have a high hydrolytic ability on ginsenoside Rb 1 by Esculin Iron Agar test. 16S rDNA analysis revealed that MBT213 was Paenibacillu sp. Crude enzyme of MBT213 strain exhibited high conversion capacity on ginsenoside Rb1 into ginsenoside Rd proven by TLC and HPLC analyses. The API ZYM kit confirmed that Paenibacillu sp. MBT213 exerted higher β-glucosidase and β-galactosidase activity than other strains. Optimum pH and temperature for crude enzyme were found at 7.0 and 35°C in hydrolysis of ginsenoside Rb 1 . After 10 d of optimal reaction conditions for the crude enzyme, ginsenoside Rb 1 fully converted to ginsenoside Rd. Ginseng roots (20%) were fermented for 14 d, and analyzed by HPLC showed that amount of ginsenoside Rb1 significantly decreased, while that of ginsenoside Rd was significantly increased. The study confirmed that the β-glucosidase produced by Paenibacillus sp. MBT213 can hydrolyze the major ginsenoside Rb1 and convert to Rd during fermentation of the ginseng. The β-glucosidase activity of this novel Paenibacillus sp. MBT213 strain may be utilized in development of variety of health foods, dairy foods and pharmaceutical products.

In this study, the physicochemical and sensory properties of Gouda cheese supplemented with microcapsules of chili pepper extract were evaluated. Microcapsules of pepper extract were prepared by coacervation technique using gum acacia-gelatin wall and chili pepper oil core. Changes in pH, lactic acid bacteria (LAB) population, and free amino acid (FAA) content after supplementation of Gouda cheese with chili pepper capsules were monitored during ripening. Texture and sensory characteristics of the Gouda cheese ripened for 6 months were evaluated. The supplementation of pepper extract microcapsules (0.5% or 1%, w/w) did not influence the pH values and LAB content of the Gouda cheese ( p <0.05) during the ripening period. While the content of total FAA increased with the ripening process in all the cheese groups ( p <0.05), no significant difference ( p <0.05) in the content of total FAA was observed among the sample groups at each time point. The addition of pepper extract microcapsules (1%, w/w) to Gouda cheese significantly decreased hardness ( p <0.05) and negatively affected sensory attributes in terms of taste and texture ( p <0.05). The results demonstrated that supplementation with 0.5% pepper extract microcapsules could provide additional bioactive ingredients, along with maintenance of the quality of Gouda cheese.

Aim: Although hypoglycemia is associated with cognitive dysfunction, including dementia, in patients with type 2 diabetes mellitus (DM), the data are equivocal. The purpose of this study was to investigate the association between hypoglycemia, dementia, and other cognitive dysfunctions., Methods: This was a prospective observational study based upon the Korea National Diabetes Program (KNDP). Among the 4540 participants in the KNDP cohort, individuals aged ⩾60years without any history of hypoglycemia or cognitive dysfunction (n=1957) were included. Nationally representative data from the Health Insurance Review and Assessment Service of Korea claim database were used to obtain a more precise determination of patient outcome., Results: During a mean follow-up period of 3.4±0.9years, 118 subjects experienced hypoglycemia-related events. The incidence of dementia and cognitive dysfunction was 7.5 cases per 1000 person-years (PY) and 0.61 cases per 1000 PY, respectively. In the subjects who experienced hypoglycemic events (relative to those who did not), the incidence of dementia was significantly higher (P=0.0139), but the incidence of cognitive dysfunction was not (P=0.1106). Hypoglycemic events were associated with dementia (HR, 2.689; 95% CI, 1.080-6.694, P=0.0335) following multiple adjustments. There was also a significant linear trend toward an increased dementia risk commensurate with an increasing number of hypoglycemic events (P=0.0286)., Conclusions: Hypoglycemia is significantly associated with the risk of dementia in Korean type 2 DM patients aged ⩾60years., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The current paper describes enhanced electrochemical capacitive performance of chemically grown Cobalt hydroxide (Co(OH) 2 ) nanorods (NRs) decorated porous three dimensional graphitic carbon foam (Co(OH) 2 /3D GCF) as a supercapacitor electrode. Freestanding 3D porous GCF is prepared by carbonizing, high internal phase emulsion (HIPE) polymerized styrene and divinylbenzene. The PolyHIPE was sulfonated and carbonized at temperature up to 850 °C to obtain graphitic 3D carbon foam with high surface area (389 m 2 g -1 ) having open voids (14 μm) interconnected by windows (4 μm) in monolithic form. Moreover, entangled Co(OH) 2 NRs are anchored on 3D GCF electrodes by using a facile chemical bath deposition (CBD) method. The wide porous structure with high specific surface area (520 m 2 g -1 ) access offered by the interconnected 3D GCF along with Co(OH) 2 NRs morphology, displays ultrahigh specific capacitance, specific energy and power. The Co(OH) 2 /3D GCF electrode exhibits maximum specific capacitance about ~1235 F g -1 at ~1 A g -1 charge-discharge current density, in 1 M aqueous KOH solution. These results endorse potential applicability of Co(OH) 2 /3D GCF electrode in supercapacitors and signifies that, the porous GCF is a proficient 3D freestanding framework for loading pseudocapacitive nanostructured materials.

Objective: To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers., Approach and Results: This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively., Conclusions: Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion., (© 2016 American Heart Association, Inc.)

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.

We developed an effective graphene transfer method for graphene/silicon Schottky diodes on a wafer as large as 6 inches. Graphene grown on a large scale substrate was passivated and sealed with a gold layer, protecting graphene from any possible contaminant and keeping good electrical contact. The Au/graphene was transferred by the tension-assisted transfer process without polymer residues. The gold film itself was used directly as the electrodes of a Schottky diode. We demonstrated wafer-scale integration of graphene/silicon Schottky diode using the proposed transfer process. The transmission electron microscopy analysis and relatively low ideality factor of the diodes indicated fewer defects on the interface than those obtained using the conventional poly(methyl methacrylate)-assisted transfer method. We further demonstrated gas sensors as an application of graphene Schottky diodes.

Background and Aims: Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM). However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice., Materials and Methods: We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP), which is the largest multi-center, prospective cohort in Korea (n = 4,350). For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA) of Korea., Results: During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19), 88 subjects (2.02%) were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY). Individuals with hypoglycemia were significantly older (59.7±10.7 vs. 53.3±10.4 years, p < 0.001), had more hospital visits (121.94±126.88 days/PY, p < 0.001), had a longer hospital stays (16.13±29.21 days/PY, p < 0.001), and incurred greater medical costs ($2,447.56±4,056.38 vs. $1,336.37±3,403.39 /PY, p < 0.001) than subjects without hypoglycemia., Conclusion: Hypoglycemia-related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system.

In the present study, the underlying apoptotic mechanism of sanggenol L was elucidated in ovarian cancer cells. Sanggenol L showed cytotoxic and antiproliferative effect in A2780, SKOV-3, and OVCAR-3 ovarian cancer cells in a concentration-dependent fashion. Consistently, sanggenol L increased sub-G1 phase population and early and late apoptotic portion in ovarian cancer cells. Also, sanggenol L activated caspase9/3, suppressed the phosphorylation of IκBα and p65 NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), attenuated the expression of Cyclin D1, and cleaved poly(adenosine diphosphate ribose -ribose) polymerase in SKOV-3, A2780, and OVCAR-3 cells. Furthermore, sanggenol L blocked nuclear translocation of NF-κB and also attenuated the expression of NF-κB related genes such as c-Myc, Cyclin D1, and Bcl-X L, Bcl-2, in lipopolysaccharide-treated SKOV-3 cells. Overall, our findings for the first time suggest that sanggenol L induces apoptosis via caspase activation and inhibition of NF-κB/IκBα phosphorylation as a potent chemotherapeutic agent for ovarian cancers., (Copyright © 2015 John Wiley & Sons, Ltd.)

A direct injection-based, simple, accurate, and robust LC-MS/MS method was developed and validated for the determination of teicoplanin in human plasma. Patient plasma samples were diluted in an aqueous buffer prior to injection into the LC-MS/MS system. Chromatographic separation was achieved using a Cadenza HS-C18 column and a gradient mixture of acetonitrile-water (both containing 0.1% formic acid) as the mobile phase at a flow rate of 0.5mL/min. The analytes were detected in multiple reaction monitoring mode with positive ion electrospray ionization. The concentration of teicoplanin was determined as the sum of six components (A3-1, A2-1, A2-2, A2-3, A2-4, and A2-5). The calibration curve was linear over a concentration range of 1-50mg/L, which covered the clinically accepted trough and therapeutic plasma levels. The intra- and inter-day precision and accuracy values were both less than 15%. This validated method was successfully applied to therapeutic drug monitoring of teicoplanin in routine clinical practice. Thus, we expect it to be useful for the determination of teicoplanin concentration in human plasma., (Copyright © 2015 Elsevier B.V. All rights reserved.)

α-Lactalbumin and β-lactoglobulin are two major whey proteins that specifically bind immunoglobulin E and are suspected as major allergens causing cow's milk allergy (CMA). Recent studies have shown that thymic stromal lymphopoietin is a critical factor linking at the interface of the body and environment to the T-helper 2 response. However, it is not known whether thymic stromal lymphopoietin expression is changed by α-lactalbumin and β-lactoglobulin in immune cells. Using RT-PCR and ELISA, the present study was conducted to examine if intravenous injection of α-lactalbumin and β-lactoglobulin increased pro-inflammatory cytokines, T-helper 2 cytokines, and thymic stromal lymphopoietin expression in several immune cells, including macrophages, mast cells, and keratinocytes. Results showed that α-lactalbumin and β-lactoglobulin induced thymic stromal lymphopoietin, interleukin-6, and tumor necrosis factor-α expression. It was concluded that the allergenicity of α-lactalbumin and β-lactoglobulin may be attributed to thymic stromal lymphopoietin induction, T-helper 2 cytokines, and pro-inflammatory cytokines.