Association between smoking and Behçet's disease: a nationwide population-based study in Korea.

BACKGROUND: There have been conflicting results about the association between Behçet's disease and smoking. Smoking has been reported to be a protective factor for Behçet's disease, whereas smoking may have a role in triggering Behçet's disease. OBJECTIVES: The aim of this study was to investigate the incidence of Behçet's disease in Korea according to smoking status using nationwide population data. METHODS: We analysed clinical data from individuals 20 years of age and older who received a health examination arranged by the Korean national insurance programme between 2009 and 2012. The incidence of Behçet's disease was analysed according to smoking status reported by individuals during their health examination. Newly diagnosed cases of Behçet's disease were identified using claims data from baseline to the date of diagnosis or until 31 December 2016. RESULTS: The risk of Behçet's disease was lower in current smokers compared with never-smokers regardless of the amount and duration of smoking. The decreased risk of Behçet's disease in current smoker persisted after adjusting for age, sex, regular exercise, drinking status, BMI, diabetes mellitus, hypertension, and dyslipidaemia, history of stroke and/or history of ischaemic heart diseases. LIMITATIONS: Genetic susceptibility or family history of Behçet's disease was not considered. CONCLUSIONS: This study found a decreased incidence of Behçet's disease in current smokers compared with never-smokers. Further investigation of the pathophysiology responsible for the negative association between smoking and Behçet's disease is needed.

Factors affecting quality of life in patients with vitiligo: a nationwide study.

BACKGROUND: Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. OBJECTIVES: To explore the QoL of patients with vitiligo and to identify factors affecting QoL. METHODS: A nationwide questionnaire-based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex-29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex-29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. RESULTS: Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20-84). The median duration of disease was 3·0 years (range 0-60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex-29. Additionally, the QoL of patients aged 20-59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. CONCLUSIONS: A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.

Incidence, prevalence, and mortality of Adamantiades-Behçet's disease in Korea: a nationwide, population-based study (2006-2015).

BACKGROUND: The epidemiology of Adamantiades-Behçet's disease varies among ethnic populations worldwide. Trends in the incidence of Adamantiades-Behçet's disease have not been investigated based on the Korean National Health Insurance database. OBJECTIVES: This study investigated the incidence and mortality of Adamantiades-Behçet's disease by age using nationwide population data in Korea. METHODS: A nationwide population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2006 to 2015. The incidence of Adamantiades-Behçet's disease was calculated by age, sex, calendar year and habitat. And comorbid metabolic diseases were also analysed in patients with Adamantiades-Behçet's disease. RESULTS: The annual incidence of Adamantiades-Behçet's disease per 100 000 person-years was 3.976 (2.587 for males and 5.373 for females) from 2006 to 2015. The incidence of Adamantiades-Behçet's disease peaked among people in their 40s (6.561 per 100 000 person-years). Incidence was significantly higher in subjects with comorbid metabolic conditions, such as diabetes mellitus, hypertension and dyslipidemia. The mortality rate per 1000 person-years increased with age in patients with Adamantiades-Behçet's disease. CONCLUSIONS: This study showed the incidence, prevalence and mortality of Adamantiades-Behçet's disease. Metabolic conditions increased the risk of Adamantiades-Behçet's disease among Koreans.

Increment of serum bilirubin as an independent marker predicting new-onset type 2 diabetes mellitus in a Korean population.

BACKGROUND AND AIMS: Several cross-sectional studies reported that serum bilirubin concentrations had an inverse association with type 2 diabetes mellitus (T2DM) prevalence. The aim of the current study was to investigate the relationship between percentage change in bilirubin levels (PCB) and incident risk of T2DM using a longitudinal model. METHODS AND RESULTS: 22,084 participants who received regular health check-ups between 2006 and 2012 were enrolled. Multivariable-adjusted Cox regression models were used to determine the hazard ratio (HR) of incident T2DM based on PCB. PCB was determined by subtracting baseline serum bilirubin level (BB) from the bilirubin level at the end of follow-up or a year before the last date of diagnosis, dividing by BB and multiplying by 100. Compared to non-diabetics, BB was lower in the diabetic group at the initial visit. There were 20,098 participants without T2DM at the initial visit; 1253 new cases occurred during follow-up. As PCB increased, T2DM incidence also increased (P < 0.001). After adjusting for confounders, the HR of incident T2DM in the highest PCB quartile was 2.08 (95% confidence interval [CI] 1.76-2.46). This trend remained significant when PCB was analyzed as a continuous variable (HR for 1-SD increment, 1.25; 95% CI 1.19-1.31). Additional analysis comparing the rate of PCB during the follow-up period revealed that the serum bilirubin level of the Incident T2DM group increased before T2DM development and decreased rapidly thereafter compared to others (P < 0.001). CONCLUSIONS: Bilirubin level increment over time is associated with T2DM development.

Atopic dermatitis is inversely associated with hepatitis B antigen positivity: a population-based cohort study.

BACKGROUND: No clear association between hepatitis B virus (HBV) infection and atopic dermatitis (AD) has been established. Some studies have reported that subjects with HBV had an increased risk of atopy; other studies reported an inverse association between HBV seropositivity and allergic diseases. OBJECTIVE: We evaluated the association between AD and hepatitis B antigen (HBsAg) positivity using Korean National Health and Nutrition Examination Survey data. METHODS: In total, 14 776 participants aged >19 years were included in the analysis. Multiple logistic regression analyses were used to evaluate the odds ratio of HBsAg positivity in association with AD and asthma. RESULTS: The prevalence of HBsAg positivity was lower in individuals with AD than in those without AD (mean [SE], 0.7% [0.4] vs. 3.7% [0.2]; P < 0.001). However, HBsAg positivity was not significantly associated with asthma (3.7% [0.2] vs. 2.8% [0.8]; P < 0.001). HBsAg positivity decreased the risk of AD significantly (OR = 0.223; 95% CI = 0.069-0.72). CONCLUSIONS: This study demonstrates an inverse association between AD and HBsAg positivity using a nationwide, population-based, cross-sectional health examination and survey.

Isolation and characterization of human intestinal Enterococcus avium EFEL009 converting rutin to quercetin.

UNLABELLED: Quercetin is a flavonol believed to have beneficial effects on human health. Rutin, found in many plants, fruits and vegetables, is metabolized by human intestinal bacteria and converted to quercetin, where it is absorbed through the intestinal epithelium. This study aimed to isolate and characterize human intestinal bacteria capable of converting rutin to quercetin. A bacterium that can metabolize rutin was isolated from human faecal samples and identified by 16S rRNA gene sequencing. The whole-cell enzymatic activities on flavonoid glycoside and the conversion profiles of the isolate were also analysed. The bacterium was identified as Enterococcus avium EFEL009 and was shown to convert rutin to isoquercetin and then to quercetin under anaerobic conditions. Microscopic analysis revealed short chains of cocci with diameters of approx. 1 µm. ß-Glucosidase was shown to be constitutively expressed in Ent. avium, while α-rhamnosidase was expressed following induction by rutin. Both enzymes were mainly localized to the cell surface. This study is the first report on the isolation of a quercetin-producing Ent. avium FEEL009, which could be a potential industrial starter bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: Quercetin is a member of the flavonoids family reported to have better cytoprotective abilities, stronger inhibition of lipopolysaccharide-induced nitric oxide production, and better chemoprevention than rutin. This is the first report on the isolation and characterization of Enterococcus avium EFEL009 from the human intestine which is capable of converting rutin to quercetin.

Relationship between polymorphisms near the IL28B gene and spontaneous HBsAg seroclearance: a systematic review and meta-analysis.

Polymorphisms near the interleukin (IL) 28B gene have been proposed to be associated with spontaneous clearance of the hepatitis C virus. The purpose of this study was to assess the relationship between IL28B polymorphisms and the rate of spontaneous hepatitis B surface antigen (HBsAg) seroclearance by means of meta-analysis. MEDLINE/PubMed and EMBASE were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analyses were mainly performed according to ethnicity. A total of 4028 cases with persistent chronic hepatitis B and 2327 spontaneously recovered controls were included from 11 studies. The single nucleotide polymorphism (SNP), rs12979860, had no significant association with HBsAg seroclearance (OR = 0.98, 95% CI: 0.84-1.14 in the dominant model; OR = 1.00, 95% CI: 0.68-1.46 in the recessive model; and OR = 0.95, 95% CI: 0.82-1.09 in the allelic model). The SNP, rs12980275, had no significant association either (OR = 1.03, 95% CI: 0.84-1.26 in the dominant model; OR = 1.17, 95% CI: 0.46-2.96 in the recessive model; and OR = 1.04, 95% CI: 0.86-1.26 in the allelic model), nor did the SNP, rs8099917 (OR = 0.94, 95% CI: 0.77-1.15 in the dominant model; OR = 0.74, 95% CI: 0.34-1.62 in the recessive model; and OR = 0.93, 95% CI: 0.77-1.13 in the allelic model). Similarly, the results of subgroup analyses by ethnicity also showed no association in either the Asian group or non-Asian group. We concluded that there was no significant association between common IL28B polymorphisms and the rate of spontaneous HBsAg seroclearance.

Use of permanent marker to deposit a protection layer against FIB damage in TEM specimen preparation.

Permanent marker deposition (PMD), which creates permanent writing on an object with a permanent marker, was investigated as a method to deposit a protection layer against focused ion beam damage. PMD is a simple, fast and cheap process. Further, PMD is excellent in filling in narrow and deep trenches, enabling damage-free observation of high aspect ratio structures with atomic resolution in transmission electron microscopy (TEM). The microstructure, composition, gap filling ability and planarization of the PMD layer were studied using dual beam focused ion beam, transmission electron microscopy, energy dispersive X-ray spectroscopy and electron energy loss spectroscopy. It was found that a PMD layer is basically an amorphous carbon structure, and that such a layer should be at least 65 nm thick to protect a surface against 30 keV focused ion beam damage. We suggest that such a PMD layer can be an excellent protection layer to maintain a pristine sample structure against focused ion beam damage during transmission electron microscopy specimen preparation.

Effects of transition metal substitutions on the incommensurability and spin fluctuations in BaFe2As2 by elastic and inelastic neutron scattering.

The spin fluctuation spectra from nonsuperconducting Cu-substituted, and superconducting Co-substituted, BaFe(2)As(2) are compared quantitatively by inelastic neutron scattering measurements and are found to be indistinguishable. Whereas diffraction studies show the appearance of incommensurate spin-density wave order in Co and Ni substituted samples, the magnetic phase diagram for Cu substitution does not display incommensurate order, demonstrating that simple electron counting based on rigid-band concepts is invalid. These results, supported by theoretical calculations, suggest that substitutional impurity effects in the Fe plane play a significant role in controlling magnetism and the appearance of superconductivity, with Cu distinguished by enhanced impurity scattering and split-band behavior.

Synthesis of sea urchin-like carbon nanotubes on nano-diamond powder.

Carbon nanotubes (CNTs) have unique atomic structure and properties, such as a high aspect ratio and high mechanical, electrical and thermal properties. On the other hand, the agglomeration and entanglement of CNTs restrict their applications. Sea urchin-like multiwalled carbon nanotubes, which have a small aspect ratio, can minimize the problem of dispersion. The high hardness, thermal conductivity and chemical inertness of the nano-diamond powder make it suitable for a wide range of applications in the mechanical and electronic fields. CNTs were synthesized on nano-diamond powder by thermal CVD to fabricate a filler with suitable mechanical properties and chemical stability. This paper reports the growth of CNTs with a sea urchin-like structure on the surface of the nano-diamond powder. Nano-diamond powders were dispersed in an attritional milling system using zirconia beads in ethanol. After the milling process, 3-aminopropyltrimethoxysilane (APS) was added as a linker. Silanization was performed between the nano-diamond particles and the metal catalyst. Iron chloride was used as a catalyst for the fabrication of the CNTs. After drying, catalyst-attached nano-diamond powders could be achieved. The growth of the carbon nanotubes was carried out by CVD. The CNT morphology was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The mean diameter and length of the CNTs were 201 nm and 3.25 microm, respectively.

Incommensurate spin-density wave order in electron-doped BaFe2 As2 superconductors.

Neutron diffraction studies of Ba(Fe(1-x)Co(x))(2)As)(2) reveal that commensurate antiferromagnetic order gives way to incommensurate magnetic order for Co compositions between 0.056 < x < 0.06. The incommensurability has the form of a small transverse splitting (0, ± ε, 0) from the commensurate antiferromagnetic propagation vector Q(AFM) = (1,0,1) (in orthorhombic notation) where ε ≈ 0.02-0.03 and is composition dependent. The results are consistent with the formation of a spin-density wave driven by Fermi surface nesting of electron and hole pockets and confirm the itinerant nature of magnetism in the iron arsenide superconductors.

Structural, optical and electrical properties of nitrogen ion implanted ZnO nanorods.

This study examined the micro-structural and electrical properties of N+-ion-implanted ZnO nanorods. Nitrogen ions with energies of 10-90 keV and beam fluxes of 10(13)-10(16) ions/cm2 were implanted on vertically-aligned ZnO nanorods. Energy dispersive X-ray spectroscopy measurements showed that N+ ions were spread uniformly over the nanorods. Extended X-ray absorption fine structure measurements revealed that the implanted N+s had partially substituted for the oxygen sites. Photoluminescence measurements showed a neutral-donor bound exciton peak at 3.36 eV and a two-electron-satellite peak at 3.33 eV independent of the ion energy and flux. The I-V characteristic curves showed that the current density was not changed by the N+ ion energy and flux much. These results strongly suggested that the N ions substituted for the oxygen sites were neutral.

Fasting plasma glucose variability in midlife and risk of Parkinson's disease: A nationwide population-based study.

AIM: Despite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). METHODS: Using the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. RESULTS: Adjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09-1.73], 1.33 (95% CI: 1.06-1.68) and 1.35 (95% CI: 1.07-1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan-Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. CONCLUSION: Increased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.

Three-dimensional changes of proximal segments in facial asymmetry patients after bilateral vertical ramus osteotomy.

The intraoral vertical ramus osteotomy (IVRO) is a useful technique for mandibular setback surgery. However, there is a tendency for lateral flaring of the proximal segments on the non-deviation side after the correction of mandibular asymmetry with this technique. The purpose of this retrospective study was to evaluate the positional changes of the proximal segments after IVRO setback in skeletal class III patients with asymmetry, using preoperative and postoperative computed tomography scan data, and to apply the results in clinical practice. A total of 28 skeletal class III patients with asymmetry who underwent bimaxillary orthognathic surgery were included. A three-dimensional cone beam computed tomography scan was obtained preoperative, at 1month postoperative, and at 1year postoperative. At 1month after the surgery, the proximal segments showed an outward rotation, lateral flaring, and anterior rotation of the condylar head. All postsurgical directional changes had returned to the preoperative state at 1year postoperative, and there was no statistically significant difference in postoperative angulation changes between the two sides. The results showed no statistical differences in the positional changes of the proximal segments between the deviation and non-deviation sides. This study reaffirms the benefits of the IVRO for a minimal bony interference between the proximal and distal segments in three dimensions, including mandibular asymmetry cases.

Prognosis of surgical hernia repair in cirrhotic patients with refractory ascites.

BACKGROUND: Abdominal wall hernias are common in patients with ascites. Elective surgical repair is recommended for the treatment of abdominal wall hernias. However, surgical hernia repair in cirrhotic patients with refractory ascites is controversial. In this study, we aimed to evaluate the outcomes of elective surgical hernia repair in patients with liver cirrhosis with and without refractory ascites. METHOD: From January 2005 to June 2018, we retrospectively reviewed the records of consecutive patients with liver cirrhosis who underwent a surgical hernia repair. RESULTS: This study included 107 patients; 31 patients (29.0%) had refractory ascites. Preoperatively, cirrhotic patients with refractory ascites had a higher median model for end-stage liver disease (MELD) score (13.0 vs 11.0, P = 0.001) than those without refractory ascites. The 30-day mortality rate (3.2% vs 0%, P = 0.64) and the risk of recurrence (hazard ratio 0.410; 95% CI 0.050-3.220; P = 0.39) did not differ significantly between cirrhotic patients with refractory ascites and cirrhotic patients without refractory ascites. Among cirrhotic patients with refractory ascites, albumin (P = 0.23), bilirubin (P = 0.37), creatinine (P = 0.97), and sodium levels (P = 0.35) did not change significantly after surgery. CONCLUSION: In advanced liver cirrhosis patients with refractory ascites, hernias can be safely treated with elective surgical repair. Mortality rate within 30 days did not differ by the presence or absence of refractory ascites. Elective hernia repair might be beneficial for treatment of abdominal wall hernia in cirrhotic patients with refractory ascites.

Pharmacokinetics and bioequivalence evaluation of gliclazide/metformin combination tablet and equivalent doses of gliclazide and metformin in healthy Korean subjects.

OBJECTIVE: To evaluate the bioequivalence of a gliclazide/metformin combination tablet (at dose of 80/500 mg) with co-administration of metformin (500 mg) and gliclazide (80 mg) as individual tablets in healthy male Korean volunteers. SUBJECTS, MATERIALS AND METHODS: The study was conducted as an open-label, randomized, 2-period crossover design in 32 healthy male Korean volunteers who received a combination tablet of gliclazide/metformin at a dose of 80/500 mg or co-administration of gliclazide and metformin as individual tablets in each study period. There was a 7-day washout period between doses. Serum concentrations of gliclazide and metformin up to 32 hours after administration were determined using a validated HPLC method with UV detection. The pharmacokinetic parameters such as AUC0-t (the area under the curve from zero to the time), AUC0- yen (the area under the curve from zero to infinity), Cmax (maximum serum concentration), tmax (time to reach Cmax) and t1/2 (terminal half-life), were analyzed by non-compartmental analysis. Analysis of variance (ANOVA) was carried out using logarithmically transformed AUC0-t, AUC0- yen and Cmax, and untransformed tmax. In addition, blood glucose concentration was also logarithmically transformed and analyzed. Tolerability and safety profiles were also investigated. RESULTS: There were no significant differences between the single combination tablet and the individual tablets in AUC0-t, AUC0- yen, Cmax and blood glucose concentration. The point estimates (90% confidence intervals) for AUC0-t, AUC0- yen and Cmax were 1.0293 (0.9476 - 1.1178), 1.0253 (0.9185 - 1.1443) and 1.0425 (0.9986 - 1.0883) for gliclazide, and 0.9887 (0.9137 - 1.0697), 0.9915 (0.9189 - 1.0697) and 0.9882 (0.9295 - 1.0505) for metformin, respectively, satisfying the bioequivalence criteria of 80 - 125% as proposed by the US FDA and the Korean legislation. Significant F test values were found between the subjects and subject nested sequence (SEQ) for AUC0-t and Cmax, indicating substantial inter-subject variation in the pharmacokinetics of gliclazide and metformin. However, a SEQ effect in the two-way crossover design did not impair the bioequivalence conclusion. No statistically significant differences were found for tmax and blood glucose concentration between two treatments. CONCLUSION: The combination tablet of gliclazide/metformin is bioequivalent to co-administration of individual tablets. As a result, the combination tablets are regarded therapeutically equivalent and exchangeable to the co-administration of individual tablets in clinical practice. Moreover, the combination tablets are expected to improve convenience and adherence to prescribed therapy and to contribute to better blood glucose control for patients with Type 2 diabetes.

Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair.

Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation, directed by local morphogen signals and mechanical cues. Here, we aimed to mimic development for regeneration of large bone defects. We hypothesized that engineered human mesenchymal condensations presenting transforming growth factor-ß1 (TGF-ß1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles promotes endochondral defect regeneration contingent on in vivo mechanical cues. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with BMP-2 + TGF-ß1 fully restoring mechanical function. Delayed in vivo ambulatory loading significantly enhanced the bone formation rate in the dual morphogen group. In vitro, BMP-2 or BMP-2 + TGF-ß1 initiated robust endochondral lineage commitment. In vivo, however, extensive cartilage formation was evident predominantly in the BMP-2 + TGF-ß1 group, enhanced by mechanical loading. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.