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Sika deer inhabiting South Korea became extinct when the last individual was captured on Jeju Island in Korea in 1920 owing to the Japanese seawater relief business, but it is believed that the same subspecies (Cervus nippon hortulorum) inhabits North Korea and the Russian Primorskaya state. In our study, mt-DNA was used to analyze the genetic resources of sika deer in the vicinity of the Korean Peninsula to restore the extinct species of continental deer on the Korean Peninsula. In addition, iSCNT was performed using cells to analyze the potential for restoration of extinct species. The somatic cells of sika deer came from tissues of individuals presumed to be Korean Peninsula sika deer inhabiting the neighboring areas of the Primorskaya state and North Korea. After sequencing 5 deer samples through mt-DNA isolation and PCR, BLAST analysis showed high matching rates for Cervus nippon hortulorum. This shows that the sika deer found near the Russian Primorsky Territory, inhabiting the region adjacent to the Korean Peninsula, can be classified as a subspecies of Cervus nippon hortulorum. The method for producing cloned embryos for species restoration confirmed that iSCNT-embryos developed smoothly when using porcine oocytes. In addition, the stimulation of endometrial cells and progesterone in the IVC system expanded the blastocyst cavity and enabled stable development of energy metabolism and morphological changes in the blastocyst. Our results confirmed that the individual presumed to be a continental deer in the Korean Peninsula had the same genotype as Cervus nippon hortulorum, and securing the individual's cell-line could restore the species through replication and produce a stable iSCNT embryo.

BackgroundThe aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section.MethodsFifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery.ResultsNo significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3-507.8 μg versus 428.0 μg [interquartile range, 305.0-507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes.ConclusionProphylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.

ObjectivesWe compared the lengths of a nasoseptal flap (NSF) and skull base according to race, age, and sex.MethodsWe performed paranasal sinus computed tomography in 19,961 adult patients between 2003 and 2022. The race of the patients was East Asian (n = 71), Caucasian (n = 71), or Middle Eastern (n = 71). The expected lengths of the NSF and anterior skull base defect were measured and analyzed according to race, age, and sex.ResultsCompared with Caucasians and Middle Easterners, East Asians had a shorter NSF length (p < 0.001) and lower ratio of the expected NSF length to the expected defect length (p < 0.001). There was no difference in the values among age groups. The expected NSF length was longer, and the ratio of the expected NSF length to the expected defect length was higher, in males than females (p < 0.001 for both).ConclusionsEast Asians and females had a shorter NSF length and lower ratio of expected NSF to surgical defect lengths after anterior skull base reconstruction compared with the other races and with males, respectively. Anatomical differences should be considered when long NSF lengths are required, such as for anterior skull base reconstruction.

This study aimed to assess the safety and effectiveness of the highly cross-linked hyaluronic acid—LBSA0103—in patients with knee osteoarthritis (OA) as per the prescribing information (PI) in South Korea. A total of 3,140 subjects aged ≥19 years were enrolled in this post-marketing surveillance (PMS) study from 2013 to 2019. The subjects received one or two injections of LBSA0103. The median duration of follow-up was 308 days. Adverse events (AEs), adverse drug reactions (ADRs), and serious AEs (SAEs) were monitored. Effectiveness was evaluated based on an index of effectiveness in accordance with the guidelines established by the Ministry of Food and Drug Safety and using a 100-mm visual analog scale (VAS) for weight-bearing pain. Overall, 250 subjects (7.96%) experienced 292 AEs and of these, unexpected AEs occurred in 114 subjects (3.63% [95% CI: 3.00–4.35]). Injection site pain was the most frequent AE reported by 81 subjects (2.58% [95% confidence intervals (CI): 2.05–3.20]). One hundred subjects experienced 108 ADRs (3.18% [95% CI: 2.60, 3.86]) and 15 unexpected ADRs were experienced by 13 subjects (0.41% [95% CI: 0.22–0.71]). Seventeen subjects experienced 22 SAEs (0.54% [95% CI: 0.32–0.87]) during the entire PMS period, and all were considered “unlikely” related to the study drug. Most AEs were mild in terms of severity and resolved during the study period. LBSA0103 was also effective in relieving symptomatic pain in knee OA patients. The condition in more than 80% of the subjects was considered to be improved when assessed by the investigators. LBSA0103 resulted in a significant reduction in the mean VAS score at 12 weeks after the first and second injections (24.79 (± 20.55) mm and 17.63 (±12.31) mm, respectively; p

PurposeThe purpose of this study was to investigate the value of C-11 methionine (MET) positron emission tomography (PET)/computed tomography (CT) in patients with intracranial germinoma (IG).Material and methodsWe conducted a retrospective analysis of 21 consecutive patients with pathologically confirmed IGs and eight patients with intracranial non-germinomas (INGs) located in a similar region. Clinical characteristics, imaging findings, and tumor markers such as α-fetoprotein (AFP) and β-human chorionic gonadotropin (HCG) were used as clinical variables. Maximum standardized uptake value (SUVmax), tumor-to-normal tissue (T/N) ratio, and visual scoring of tumor were used as MET PET parameters.ResultsAll IGs were well visualized on MET PET with a three-grade visual scoring system. In addition, SUVmax of IGs was higher than that of INGs (P = 0.005). Pre-treatment (Pre-Tx) T/N ratio was significantly correlated with pre-Tx serum HCG (P = 0.031). Moreover, MET PET parameters showed significant associations with tumor location, sex, KRAS variant, and symptoms.ConclusionMET PET/CT could be a useful diagnostic tool in patients suspected of having IGs. In addition, the MET avidity of tumor is a potential surrogate biomarker of HCG, which has been used as a diagnostic marker for IGs. Tumor MET parameters also had significant differences according to tumor locations, sex, symptoms, and KRAS mutation. However, MET avidity of tumors had no significant prognostic value.

ObjectivesAcute phase reactants (APRs) are proteins altered by inflammation and are regarded as surrogate markers representing inflammatory status. This study evaluated changes of albumin (Alb), prealbumin (Palb), and ischemia-modified albumin (IMA) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in response to alterations in disease activity and the correlation between disease activity and Alb, Palb, and IMA.MethodsFifty-nine patients with AAV registered in the prospective SHAVE cohort, who had available serial blood samples at least three months apart were included (indicated as pre and post). Correlation analysis and linear regression were carried out to determine the relationship between continuous variables. Alb, Palb, and IMA levels in 40 healthy controls (HCs) were compared with patients with AAV.ResultsComparison of Alb, Palb, and IMA levels in HCs and in patients at initial (pre) and follow-up (post) time points revealed that Alb levels significantly increased following the improvement of disease activity and were comparable between HCs and patients at follow-up (post). Meanwhile, there was no significant difference noted in Palb and IMA levels after the decrease of disease activity. While initial (pre) Alb and Palb were significantly associated with BVAS, a subgroup analysis of patients with new-onset disease showed Palb was no longer significantly associated with Birmingham Vasculitis Activity Score (BVAS). Multivariate linear regression showed Alb level (standardized β = -0.377; 95% confidence interval: -5.623, -1.260; p = 0.003) was an independent predictor of BVAS at baseline.ConclusionsAmong Alb, Palb, and IMA, we found that Alb could be a useful marker indicating disease activity in patients with AAV.

How can we accurately and efficiently decompose a tensor stream? Tensor decomposition is a crucial task in a wide range of applications and plays a significant role in latent feature extraction and estimation of unobserved entries of data. The problem of efficiently decomposing tensor streams has been of great interest because many real-world data dynamically change over time. However, existing methods for dynamic tensor decomposition sacrifice the accuracy too much, which limits their usages in practice. Moreover, the accuracy loss becomes even more serious when the tensor stream has an inconsistent temporal pattern since the current methods cannot adapt quickly to a sudden change in data. In this paper, we propose DAO-CP, an accurate and efficient online CP decomposition method which adapts to data changes. DAO-CP tracks local error norms of the tensor streams, detecting a change point of the error norms. It then chooses the best strategy depending on the degree of changes to balance the trade-off between speed and accuracy. Specifically, DAO-CP decides whether to (1) reuse the previous factor matrices for the fast running time or (2) discard them and restart the decomposition to increase the accuracy. Experimental results show that DAO-CP achieves the state-of-the-art accuracy without noticeable loss of speed compared to existing methods.

BackgroundSmoking or weight loss is a risk of tuberculosis (TB) development. However, the impact of weight change after smoking cessation on the occurrence of TB remains elusive. We aimed to determine the relationship between weight change after smoking cessation and the risk of TB development.MethodsWe conducted a population-based cohort study using the national database in Republic of Korea. Of the 10,490,491 subjects who underwent health check-up in 2009, we enrolled 9,953,124 subjects without a previous TB history and followed them until 2017. We divided all study participants into the following three groups: never, former, and current smokers. The primary endpoint was newly developed TB.ResultsAmong 9,953,124 subjects analyzed, 5,922,845 (59.5%) were never smokers, 1,428,209 (14.4%) were former smokers, and 2,602,080 (26.1%) were current smokers. The risk of TB development was significantly higher in current smokers than in never smokers (adjusted hazard ratio (aHR) 1.158; 95% confidence interval [CI] 1.131-1.186). Among current smokers, individuals who stopped smoking and maintained weight after baseline evaluation had a significantly lower risk of TB development compared with those who continued to smoke (aHR 0.771; 95% CI 0.741-0.892). However, even after smoking cessation, individuals who lost weight were at a significantly higher risk of TB development compared with those who continued to smoke (aHR 1.327; 95% CI 1.119-1.715).ConclusionsOur findings suggest that smoking is a risk factor for TB and weight maintenance (neither gaining or losing) after quitting smoking might reduce the risk of TB development.

ObjectivesThe objective of this study was to investigate current perception and expected price of personal sound amplification products (PSAPs) and to analyze influencing factors through multi-center hospital-based surveys of outpatients, caregivers, and hearing experts.MethodsA multi-center exploratory cross-sectional study was conducted in two groups of respondents with two separate surveys: 1) a perception survey of patients and caregivers who visited an otorhinolaryngology outpatient clinic in 5 general hospitals and 2) an opinion survey of hearing specialists about the expected price of PSAPs. A total of 197 outpatient visitors responded to the perception survey, and 42 hearing specialists responded to the opinion survey.ResultsOverall perception score (18 questions) was 3.04 (95% CI, 3.00-3.09). When 5 categories of perception (knowledge, needs, cost, expectation, and information categories) were analyzed, cost and expectation showed the highest scores of 3.33 (95% CI, 3.21-3.44) and 3.33 (95% CI, 3.27-3.40), respectively, and needs showed the lowest score of 2.23 (95% CI, 1.97-2.49). The ≥ 60-year-old group showed significantly higher perception of PSAPs (P = 0.002), and the individuals with greater severity of subjective hearing loss showed significantly higher perception of PSAPs (P = 0.002). The expected price of PSAPs of the outpatient visitors was 933.9 USD (95% CI, 811.9-1056.0) per ear. Mean expected price of PSAPs of hearing specialists was 291.3 USD (95% CI, 238.2-344.3) per ear.ConclusionThe perception rate of PSAPs was very low, and there was a discrepancy in the expected price of PSAPs between patients/caregivers and hearing experts. Hearing specialists should make effort to improve perception of PSAPs.

BackgroundAlthough accumulating evidence suggests a more extensive reduction of low-density lipoprotein cholesterol (LDL-C), it is unclear whether a higher statin dose is more effective and cost-effective in the Asian population. This study compared the efficacy, safety, and cost-effectiveness of atorvastatin 20 and 10 mg in high-risk Asian patients with hypercholesterolemia.MethodsA 12-week, open-label, parallel, multicenter, Phase IV randomized controlled trial was conducted at ten hospitals in the Republic of Korea between October 2017 and May 2019. High-risk patients with hypercholesterolemia, defined according to 2015 Korean guidelines for dyslipidemia management, were eligible to participate. We randomly assigned 250 patients at risk of atherosclerotic cardiovascular disease to receive 20 mg (n = 124) or 10 mg (n = 126) of atorvastatin. The primary endpoint was the difference in the mean percentage change in LDL-C levels from baseline after 12 weeks. Cost-effectiveness was measured as an exploratory endpoint.ResultsLDL-C levels were reduced more significantly by atorvastatin 20 mg than by 10 mg after 12 weeks (42.4% vs. 33.5%, p < 0.0001). Significantly more patients achieved target LDL-C levels (ConclusionIn high-risk Asian patients with hypercholesterolemia, atorvastatin 20 mg was both efficacious in reducing LDL-C and cost-effective compared with atorvastatin 10 mg.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Periodontitis, as chronic inflammatory destructive disease, is associated metabolic syndromes bidirectionally. Toothbrushing is an essential and important way to manage periodontitis through mechanical removal of biofilm at periodontal tissue. We aimed to assess the association between toothbrushing frequency and the prevalent NAFLD in nationally representative Korean adults. Among adults aged 19 years and older who participated in the Korea National Health and Nutrition Examination Survey in 2010, a total of 6,352 subjects were analyzed. NAFLD was defined as fatty liver index ≥60. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). An inverse association between toothbrushing frequency and NAFLD was found. The adjusted ORs (95% CIs) of NALFD was 0.56 (0.35-0.91) in the group who performed toothbrushing ≥ 3 per day compared to the group that performed toothbrushing ≤ 1 per day. For those with toothbrushing frequency ≤1 per day, the adjusted OR (95% CIs) of NAFLD was 2.26 (1.22-4.19) in smokers and 4.52 (1.97-10.38) in subjects with diabetes mellitus (DM), compared to those without the disease and with toothbrushing frequency ≥2 per day, respectively. Our results indicate that higher frequency of toothbrushing is inversely associated with NAFLD. As a modifiable oral habit, regular toothbrushing may be recommended to lower risk of NAFLD, especially in high risk groups such as smokers and diabetic patients.

[This corrects the article DOI: 10.1371/journal.pone.0245481.].

Soft robots have been extensively researched due to their flexible, deformable, and adaptive characteristics. However, compared to rigid robots, soft robots have issues in modeling, calibration, and control in that the innate characteristics of the soft materials can cause complex behaviors due to non-linearity and hysteresis. To overcome these limitations, recent studies have applied various approaches based on machine learning. This paper presents existing machine learning techniques in the soft robotic fields and categorizes the implementation of machine learning approaches in different soft robotic applications, which include soft sensors, soft actuators, and applications such as soft wearable robots. An analysis of the trends of different machine learning approaches with respect to different types of soft robot applications is presented; in addition to the current limitations in the research field, followed by a summary of the existing machine learning methods for soft robots.

ObjectivesPrevious studies have shown that adipokines may serve as potential biomarkers reflecting disease activity in various autoimmune diseases. Here, we investigated the relationship between four adipokines and clinical/laboratory findings in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsSera from 63 patients with MPA and GPA who were registered in a prospective cohort were used to detect serum levels of adiponectin, chemerin, resistin, and vaspin using commercial enzyme-linked immunosorbent assay kits. Associations between adipokines and clinical and laboratory data was assessed using Pearson's correlation analysis.ResultsThe median age was 65.0 years, 24 patients were male, and 42 patients were diagnosed with MPA. The median levels of adiponectin, chemerin, resistin, and vaspin in patient sera were 13.9 ng/mL, 9.2 ng/mL, 23.7 ng/mL, and 0.1 ng/mL, respectively. A significant correlation between chemerin level and five-factor score (FFS) was found (r = 0.320, p = 0.011), and resistin was correlated with both Birmingham vasculitis activity score and FFS (r = 0.256, p = 0.043 and r = 0.320, p = 0.011). Regarding laboratory data, adiponectin level was associated with creatinine, and chemerin level was associated with creatinine, albumin, and erythrocyte sedimentation rate (ESR). On the other hand, resistin was found to be associated with white blood cell count, creatinine, ESR, and C-reactive protein. Age did not have a significant impact on the levels of adipokines.ConclusionsThe expression of adipokines in the sera of patients with MPA and GPA differs depending on clinical and laboratory features, and serum resistin may be suggested as a potential biomarker reflecting disease activity.

Cell culture is widely utilized to study the cellular and molecular biology of different neuronal cell populations. Current techniques to study enriched neurons in vitro are primarily limited to embryonic/neonatal animals and induced pluripotent stem cells (iPSCs). Although the use of these cultures is valuable, the accessibility of purified primary adult neuronal cultures would allow for improved assessment of certain neurological diseases and pathways at the cellular level. Using a modified 7-step immunopanning technique to isolate for retinal ganglion cells (RGCs) and amacrine cells (ACs) from adult mouse retinas, we have successfully developed a model of neuronal culture that maintains for at least one week. Isolations of Thy1.2+ cells are enriched for RGCs, with the isolation cell yield being congruent to the theoretical yield of RGCs in a mouse retina. ACs of two different populations (CD15+ and CD57+) can also be isolated. The populations of these three adult neurons in culture are healthy, with neurite outgrowths in some cases greater than 500μm in length. Optimization of culture conditions for RGCs and CD15+ cells revealed that neuronal survival and the likelihood of neurite outgrowth respond inversely to different culture media. Serially diluted concentrations of puromycin decreased cultured adult RGCs in a dose-dependent manner, demonstrating the potential usefulness of these adult neuronal cultures in screening assays. This novel culture system can be used to model in vivo neuronal behaviors. Studies can now be expanded in conjunction with other methodologies to study the neurobiology of function, aging, and diseases.

BackgroundThe level of fasting plasma glucose (FPG) is positively associated with intraocular pressure. Diabetes causes early structural changes of retina, especially on ganglion cell layer. In this regard, the FPG level itself may also show an independent association with open angle glaucoma (OAG) development in general population. Herein, we investigate the association of the FPG level with the incidence of OAG.MethodsUsing nationally representative data from the Korean National Health Insurance System, 374,376 subjects ≥40 years of age without OAG who underwent health examinations from 2009 to 2013 were enrolled and followed to the end of 2014. Incident cases of OAG using the International Classification of Diseases 10 codes and medication information were analyzed based on the levels of FPG.ResultsSubjects with the highest FPG level (≥160 mg/dL), compared with the lowest level (ConclusionsThis nationwide population-based cohort study showed that the fasting glucose was associated with an increased risk of OAG. These findings suggest that subjects with high FPG levels require special attention when screening for glaucoma.

We investigated the association between nonalcoholic fatty liver disease (NAFLD) and gastrointestinal tract cancer in the general population. Retrospective data on individuals aged ≥20 years who received healthcare checkups from January 1, 2009 to December 31, 2009 were analyzed using the National Health Insurance Database in Korea. NAFLD was defined based on the fatty liver index (FLI ≥60). The primary outcome was newly diagnosed esophageal, stomach, or colorectal cancer using ICD-10 codes during follow-up until 31 December 2017. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Among 8,120,674 subjects, 936,159 adults (11.5%) were identified as having NAFLD. Their mean age was 46.7 ± 14.1 years, and 52.1% were male. During the follow-up period (7.2 years), 3,792 esophageal, 57,292 stomach and 68,769 colorectal cancer cases were identified. FLI ≥60 was significantly associated with the development of esophageal (HR 2.10, 95% CI 1.88-2.35), stomach (HR 1.18, 95% CI 1.14-1.22), and colon cancer (HR, 1.23, 95% CI 1.19-1.26) after multivariable adjustment. Compared to subjects without NAFLD, all-cause mortality in patients with esophageal (HR 1.46, 95% CI 1.28-1.67), stomach (HR 1.26, 95% CI 1.18-1.34), and colorectal cancer (HR 1.16, 95% CI 1.10-1.22) was significantly increased in subjects with NAFLD (FLI ≥60). NAFLD defined using FLI was a good predictive indicator for GI tract malignancy and all-cause mortality in the general population. Subjects with NAFLD are needed for active surveillance of esophageal, stomach, and colorectal cancers.

Neonatal vitamin D deficiency is common and is associated with development of pulmonary disease in children and adults. While the role of vitamin D in normal lung development is well established, the association between vitamin D deficiency and bronchopulmonary dysplasia (BPD) remains unclear. The present meta-analysis was conducted to evaluate the relationship between vitamin D and BPD. We identified relevant studies (n = 8) using the PubMed, EMBASE, Cochrane Library, and KoreaMed databases and applied the Newcastle-Ottawa Scale to assess the methodological components of each study, and used I2 statistic to evaluate heterogeneity. Comprehensive Meta-Analysis software version 3.3 was used for the statistical analysis. A total of 909 infants were included, of whom 251 (27.6%) were diagnosed with BPD. We found that both vitamin D deficiency at birth (four studies; OR 2.405; 95% CI 1.269 to 4.560; p = 0.007) and low levels of vitamin D at birth (four studies; standardized mean difference -1.463; 95% CI -2.900 to -0.027; p = 0.046) were associated with BPD. The compiled data suggest that antenatal vitamin D deficiency and low vitamin D levels are associated with neonatal BPD.

We aimed to investigate the association of various obesity parameters and phenotypes with hypertension in nationally representative Korean adults. Among adults aged 19 years and older who participated in the Korea National Health and Nutrition Examination Survey in 2008-2010, a total of 16,363 subjects (8,184 men and 8,179 women) were analyzed. Hypertension was defined as blood pressure of 140/90 mm Hg or higher or taking antihypertensive medication. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Higher obesity parameters [body mass index (BMI) representing general obesity, waist circumference (WC) representing central obesity, and percentage body fat (PBF) representing elevated body fat] were consistently associated with increased odds of prevalent hypertension (OR, 7.54; 95% CI, 5.89-9.65 for BMI ≥30 vs. 18.5-23; OR, 3.97; 95% CI, 3.41-4.63 for WC ≥95 cm in males and ≥90 cm in females vs.

Smoking cessation reduces the cardiovascular risk but increases body weight. We investigated the risk of subsequent myocardial infarction and ischemic stroke according to weight gain after smoking cessation, using a nationwide population based cohort. We enrolled 3,797,572 Korean adults aged over 40 years who participated in national health screenings between 2009 and 2010. Subjects who quit smoking were classified into three subgroups according to the weight change between baseline and 4 years prior. Myocardial infarctions and ischemic strokes were followed until the end of 2015. We compared the hazard ratios among smoking cessation subgroups, non-smokers, and current smokers. The mean changes in weight (1.5 ± 3.9 kg) of the smoking cessation group were higher than those of the other groups (p < 0.0001). A total of 31,277 and 46,811 subjects were newly diagnosed with myocardial infarction and ischemic stroke, respectively. Regardless of weight change, all subgroups of smoking cessation had significantly less risk than current smokers. The subgroup of smoking cessation with weight gain over 4kg showed the lowest risk for myocardial infarctions (hazard ratio 0.646, 95% confidence interval 0.583-0.714, p < 0.0001) and ischemic strokes (hazard ratio 0.648, 95% confidence interval 0.591-0.71, p < 0.0001) after multivariable adjustment. In conclusion, weight gain after smoking cessation did not adversely affect the cardiovascular protective effect.

Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology.

BackgroundTo evaluate the impact of macrophage activation syndrome (MAS) on clinical features in patients with Kikuchi-Fujimoto disease (KFD) and to compare the features of MAS in KFD with those of adult-onset Still's disease (AOSD) and systemic lupus erythematosus (SLE).MethodsThe medical records of febrile patients hospitalised with KFD between November 2005 and April 2017 were reviewed. Patients fulfilling the 2016 classification criteria for MAS were classified as having MAS. Clinical and laboratory features of patients with KFD with and without MAS were evaluated. Poor hospitalisation outcomes were defined as intensive care unit admission or in-hospital mortality. The treatment outcomes of MAS in KFD, AOSD, and SLE were also compared.ResultsAmong 78 patients hospitalised with KFD, 24 (30.8%) patients had MAS during admission. Patients with KFD and MAS more frequently required glucocorticoid treatment (66.7% vs 40.7%, p = 0.036) and had longer hospital stays than patients with KFD without MAS (12.5 vs 8.5 days, pConclusionsThe presence of MAS in KFD was associated with adverse clinical outcomes including higher steroid usage and worse hospitalisation outcomes. However, compared to those with AOSD and SLE, patients with MAS and KFD were less likely to require long-term glucocorticoid treatment.

BackgroundDepression, one of the most costly and common mental disorders, is reported to be associated with lower quality of life (QoL) in several studies. Improved understanding of the associated factors with QoL is necessary to optimize long-term outcomes and reduce disability in patients with depression. Therefore, the aim of this study was to identify factors that are associated with lower QoL among patients with depression.MethodsThe study was based on the Korea National Health and Nutrition Examination Survey, a cross-sectional health examination, years 2008 to 2014. The final analyzed sample consisted of a total of 1,502 study subjects who had been diagnosed by clinicians as having depression. A multivariate logistic regression model was performed to exam the association between the clinical characteristics (age, sex, demographic and health-related characteristics) and QoL. Analysis of covariance was also used to analyze EQ-5D according to mental health.ResultsOlder age, lower level of education, lower income, worse subjective perception of health, unemployment, obesity and mental health struggles were found to be significantly associated with low QoL in depressive individuals after adjustment for multiple covariates.ConclusionsThis study has outlined grounding data in identifying patients who are at risk of QoL impairment. Policy makers should direct their interests to these individuals and provide appropriate management.

BackgroundOverweight is known as a risk factor for ischemic stroke. However, the effect of weight change on the development of ischemic stroke remains controversial. We investigated the relationship between weight change and the risk of ischemic stroke using a nationwide population-based cohort.MethodsOur study enrolled 11,084,683 participants (Mean age 49.7±13.5 years, range 20-114 years) in the Korean National Health Screening Program from 2009 to 2012. Weight change was calculated using the difference between the baseline weight and the weight at health screening four years prior to the baseline. The occurrence of newly-diagnosed ischemic stroke was observed until the end of 2015. We categorized the study population according to weight change and performed multivariable analysis to compare the risk.ResultsIschemic stroke was newly diagnosed in 113,591 subjects. The crude incidence rates of ischemic stroke per 1000 person-years according to the change in body weight were 3.059, 1.906, and 1.491 in the ConclusionsThe risk of ischemic stroke was gradually increased in those who lost or gained more than 5% of their weight over four years, after adjusting for confounders. We should be aware of the increased risk of ischemic stroke in people who undergo weight change and should identify and manage the cause of weight change.

Because of the recent increase in the demand for fresh produce, contamination of raw food products has become an issue. Foodborne diseases are frequently caused by the infection of leguminous plants by human bacterial pathogens. Moreover, contamination by Vibrio cholerae, closely related with Vibrio vulnificus, has been reported in plants and vegetables. Here, we investigated the possibility of Vibrio vulnificus 96-11-17M, an opportunistic human pathogen, to infect and colonize Arabidopsis thaliana plants, resulting in typical disease symptoms at 5 and 7 days post-inoculation in vitro and in planta under artificial and favorable conditions, respectively. RNA-Seq analysis revealed 5,360, 4,204, 4,916 and 3,741 differentially expressed genes (DEGs) at 12, 24, 48 and 72 h post-inoculation, respectively, compared with the 0 h time point. Gene Ontology analysis revealed that these DEGs act in pathways responsive to chemical and hormone stimuli and plant defense. The expression of genes involved in salicylic acid (SA)-, jasmonic acid (JA)- and ethylene (ET)-dependent pathways was altered following V. vulnificus inoculation. Genetic analyses of Arabidopsis mutant lines verified that common pathogen-associated molecular pattern (PAMP) receptors perceive the V. vulnificus infection, thus activating JA and ET signaling pathways. Our data indicate that the human bacterial pathogen V. vulnificus 96-11-17M modulates defense-related genes and host defense machinery in Arabidopsis thaliana under favorable conditions.

BACKGROUND:Little is known about the causality and pathological mechanism underlying the association of seasonal variation with myocardial injury in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVE:We evaluated the association of seasonal effect with myocardial injury using cardiovascular magnetic resonance (CMR) imaging in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS:In 279 patients undergoing primary PCI for STEMI, CMR was performed for a median of 3.3 days after the index procedure. Of these, STEMI occurred in 56 patients in the winter (Winter group), 80 patients in the spring (Spring group), 76 patients in the summer (Summer group), and 67 patients in the autumn (Autumn group), respectively. We compared myocardial infarct size, extent of area at risk (AAR), myocardial salvage index (MSI) and microvascular obstruction (MVO) area as assessed by CMR according to the season in which STEMI occurred. RESULTS:In the CMR analysis, the myocardial infarct size was not significantly different among the Winter group (21.0 ± 10.5%), the Spring group (19.6 ± 11.5%), the Summer group (18.6 ± 10.6%), and the Autumn group (21.1 ± 11.3%) (P = 0.475). The extent of AAR, MSI, and MVO areas were similar among the four groups. In the subgroup analysis, myocardial infarct size, extent of AAR, MSI, and MVO were not significantly different between the Harsh climate (winter + summer) and the Mild climate (spring + autumn) groups. CONCLUSIONS:Seasonal influences may not affect advanced myocardial injury in STEMI patients undergoing primary PCI.

BACKGROUND:The association of metabolic syndrome (MetS) with the development of Parkinson disease (PD) is currently unclear. We sought to determine whether MetS and its components are associated with the risk of incident PD using large-scale cohort data for the whole South Korean population. METHODS AND FINDINGS:Health checkup data of 17,163,560 individuals aged ≥40 years provided by the National Health Insurance Service (NHIS) of South Korea between January 1, 2009, and December 31, 2012, were included, and participants were followed up until December 31, 2015. The mean follow-up duration was 5.3 years. The hazard ratio (HR) and 95% confidence interval (CI) of PD were estimated using a Cox proportional hazards model adjusted for potential confounders. We identified 44,205 incident PD cases during follow-up. Individuals with MetS (n = 5,848,508) showed an increased risk of PD development compared with individuals without MetS (n = 11,315,052), even after adjusting for potential confounders including age, sex, smoking, alcohol consumption, physical activity, income, body mass index, estimated glomerular filtration rate, and history of stroke (model 3; HR, 95% CI: 1.24, 1.21-1.27). Each MetS component was positively associated with PD risk (HR, 95% CI: 1.13, 1.10-1.16 for abdominal obesity; 1.13, 1.10-1.15 for hypertriglyceridemia; 1.23, 1.20-1.25 for low high-density lipoprotein cholesterol; 1.05, 1.03-1.08 for high blood pressure; 1.21, 1.18-1.23 for hyperglycemia). PD incidence positively correlated with the number of MetS components (log-rank p < 0.001), and we observed a gradual increase in the HR for incident PD with increasing number of components (p < 0.001). A significant interaction between age and MetS on the risk of incident PD was observed (p for interaction < 0.001), and people aged ≥65 years old with MetS showed the highest HR of incident PD of all subgroups compared to those

Preservation of residual hearing after cochlear implant is an important issue with regards to hearing performance. Various methods of steroid administration have been widely used in clinical practice to reduce inflammation and preserve residual hearing. Here we compare the effect of different routes of dexamethasone administration on intracochlear inflammation and residual hearing in guinea pig ears. Dexamethasone was delivered into the guinea pigs either through intracochlear, intratympanic or systemic route. The intracochlear concentration of dexamethasone, residual hearing, inflammatory cytokines and histopathologic changes were evaluated over time. A higher intracochlear dexamethasone concentration was observed after intracochlear administration than through the other routes. Residual hearing was better preserved with local dexamethasone administration as was supported by the reduced inflammatory cytokines, more hair cell survival and less severe intracochlear fibrosis and ossification concurrently seen in the local delivery group than in the systemic group. The results demonstrate that local dexamethasone delivery can reduce intracochlear inflammation and preserve residual hearing better than in systemically administered dexamethasone.

Despite of numerous evidences that elevated serum lactate levels were associated with unfavorable outcomes, there have been no study demonstrated an optimal cutoff of serum lactate in unselected patients. This study was aimed to evaluate the prognostic property of lactate, and to identify a cutoff of serum lactate level for predicting 30-day in-hospital mortality among unselected patients presenting to the emergency department (ED).We performed a retrospective observational study from January 2010 to December 2016. 61,151 patients were used for propensity score analysis after exclusion. 14,015 patients who underwent lactate test at ED arrival were enrolled for final analysis.The average treatment effect (ATE) of carrying out a lactate test on 30-day in-hospital mortality was 0.53% (adjusted odds ratio (OR) = 1.013, p = 0.19; 95% confidence interval (CI), 0.997-1.013). Adjusted OR of serum lactate calculated from multivariable analysis was 1.09 (p < 0.001; 95% CI, 1.07-1.10). The area under a ROC curve (AUC) of serum lactate was 0.711 (p < 0.001; 95% CI, 0.703-0.718). The sensitivity, specificity, and positive and negative predictive values for the cutoff > 2.6 mmol/L were 56.7%, 74.3%, 20.8%, and 93.5%, respectively. Mortality of the high-lactate group (> 2.6 mmol/L) was significantly higher than that of the low lactate group (≤ 2.6 mmol/L) (20.8% vs. 6.5%, difference = 14.3%, p < 0.01; 95% CI, 13.0% - 15.7%).A serum lactate level > 2.6 mmol/L predicted 30-day in-hospital mortality in unselected patients who arrived to the ED and were admitted to the hospital. Additionally, serum lactate test in the ED could be an effective screening method for identifying low risk patients.

It is unclear how systemic administration of mesenchymal stem cells (MSCs) controls local inflammation. The aim of this study was to evaluate the therapeutic effects of human MSCs on inflammatory arthritis and to identify the underlying mechanisms. Mice with collagen antibody-induced arthritis (CAIA) received two intraperitoneal injections of human bone marrow-derived MSCs. The clinical and histological features of injected CAIA were then compared with those of non-injected mice. The effect of MSCs on induction of regulatory T cells was examined both in vitro and in vivo. We also examined multiple cytokines secreted by peritoneal mononuclear cells, along with migration of MSCs in the presence of stromal cell-derived factor-1 alpha (SDF-1α) and/or regulated on activation, normal T cell expressed and secreted (RANTES). Sections of CAIA mouse joints and spleen were stained for human anti-nuclear antibodies (ANAs) to confirm migration of injected human MSCs. The results showed that MSCs alleviated the clinical and histological signs of synovitis in CAIA mice. Peritoneal lavage cells from mice treated with MSCs expressed higher levels of SDF-1α and RANTES than those from mice not treated with MSCs. MSC migration was more prevalent in the presence of SDF-1α and/or RANTES. MSCs induced CD4+ T cells to differentiate into regulatory T cells in vitro, and expression of FOXP3 mRNA was upregulated in the forepaws of MSC-treated CAIA mice. Synovial and splenic tissues from CAIA mice receiving human MSCs were positive for human ANA, suggesting recruitment of MSCs. Taken together, these results suggest that MSCs migrate into inflamed tissues and directly induce the differentiation of CD4+ T cells into regulatory T cells, which then suppress inflammation. Thus, systemic administration of MSCs may be a therapeutic option for rheumatoid arthritis.

OBJECTIVE:The proportion of elderly patients with rheumatoid arthritis (RA) is continuously growing as a result of the increasing aging population. We compared disease activity between different age groups, and evaluated the clinical factors associated with high disease activity. METHODS:This cross-sectional study analyzed the data of RA patients enrolled in the Korean College of Rheumatology Biologics registry (KOBIO-RA) between 2012 and 2014. Disease activity between elderly (age ≥ 65 years) and non-elderly patients (age < 65 years) was compared, and the association of clinical factors with high disease activity was assessed using a multivariate logistic regression model. RESULTS:Of 1,227 patients in KOBIO-RA, 244 patients with RA were aged 65 years or over. In elderly patients, the proportion of men was higher (P = 0.012), and the duration of disease was longer (P < 0.001) compared with non-elderly patients. The elderly group showed a higher incidence of comorbidity (P < 0.001), and less use of methotrexate (P = 0.004). Assessment of disease activity using various composite measures showed a higher proportion of high disease activity in elderly patients than non-elderly patients. Longer disease duration, presence of comorbidity, and non-use of methotrexate were independently associated with high disease activity (P = 0.002, P < 0.001, and P = 0.029, respectively). CONCLUSIONS:At enrollment of KOBIO-RA, elderly patients showed higher disease activity compared with non-elderly patients. Disease duration, use of methotrexate, and comorbidity are associated with disease activity control in Korean patients with RA.

Analyzing extracellular vesicles (EVs) is an attractive approach to diagnosis of prostate diagnosis. However, existing methods of EVs isolation have low efficiency, purity, and long process time, and therefore have low diagnostic ability. To solve these the problems, a two-phase system is adapted to isolate EVs from a patient's urine. Urine from 20 prostate cancer (PCA) patients and 10 benign prostate hyperplasia patients was used to quantify the EVs-isolation ability of an aqueous two-phase system (ATPS) and to compare the diagnostic ability of ATPS with that of the conventional diagnosis method. An optimized ATPS isolates EVs with ~100% efficiency within ~30 min, with 14 times as high as achieved by ultracentrifugation. Afterward, PCR and ELISA are used to detect EVs derived from PCA cells in urine. The results demonstrate that diagnostic ability based on ATPS is better than other conventional diagnostic methods. ATPS can obtain a high quality and quantity of EVs from patients' urine. EVs contain cancer-related protein and genes, so these abundant sources enable diagnosis with high specificity and sensitivity. Therefore, ATPS is a useful tool to increase the specificity and sensitivity of diagnosis.

BACKGROUND:Little is known about the correlation between microbiological yield and radiographic activity, on chest computed tomography (CT), in suspected pulmonary tuberculosis (PTB) cases, despite CT being widely used, clinically. METHODS:We used multicenter retrospective data, obtained from medical records, focusing on the diagnostic performance for definite PTB. We categorized patients into four groups, by radiographic activity: definitely active, probably active, indeterminate activity, and probably inactive. RESULTS:Of the 650 patients included, 316 had culture-confirmed PTB; 190 (29.2%), 323 (49.7%), 70 (10.8%), and 67 (10.3%) were classified into the definitely active, probably active, indeterminate activity, and probably inactive groups, respectively. The corresponding observed culture rates for CT radiographic activity were 61.6%, 60.7%, 4.3% and 0%, respectively. When not only culture rates but TB-PCR and histological results were taken into consideration as definite PTB, it showed 66.6%, 67.2%, 14.3%, and 0% of each CT radiographic activity, respectively. Regarding the diagnostic performance for definite PTB, radiographic activity displayed high sensitivity (97.1%, 95% confidence interval (CI), 94.6-98.5) and negative predictive values (92.7%, 95% CI, 86.6-96.2), considered definitely and probably active PTB. Apart from PTB, other etiologies, according to radiographic activity, were predominantly respiratory infections such as bacterial pneumonia and non-tuberculous mycobacterial infection. CONCLUSIONS:Radiographic activity showed good diagnostic performance, and can be used easily in clinical practice. However, clinicians should consider other possibilities, because radiologic images do not confirm microbiological PTB.

PURPOSE:To examine the competing risks of stillbirth versus infant death and to evaluate the optimal time of delivery in the population of small for gestational age (SGA) and non-SGA late preterm and term fetuses. METHODS:This was a retrospective national cohort study of all singleton births between 34 0/7 and 42 6/7 weeks of gestation using the Korean vital statistics (n = 2,106,159). We compared the risk of infant mortality with a composite of fetal-infant mortality risk that would occur after expectant management for one additional week and evaluated the optimal time of delivery, in SGA and non-SGA pregnancies. RESULTS:In the total population, the risk of expectant management became significantly higher than the risk of delivery, at 39 weeks and beyond, similar with non-SGA group. In the SGA group, the risk of stillbirth was significantly greater at all GAs than for non-SGA pregnancies, and the risk of infant death was significantly increased until 38 weeks (25.8 per 10,000 live births, 95% CI 20.11-32.47), and the risk of stillbirth was significantly increased at 41 weeks (11.65 per 10,000 ongoing pregnancies, 95% CI 6.95-18.09), compared to 39 weeks (12 per 10,000 live births, 95% CI 8.98-15.64 and 5.12 per 10,000 ongoing pregnancies, 95% CI 3.84-6.66, respectively). CONCLUSION:In Korean women, delivery between 39 and 41 weeks minimizes fetal/infant mortality, in non-SGA pregnancies. In uncomplicated SGA pregnancies, delivery between 39 and 40 weeks can be considered to decrease risk of infant death and stillbirths.

OBJECTIVE:A quantitative basis for the use of dipstick urinalysis for risk assessment of all-cause mortality is scarce. Therefore, we investigated the association between dipstick proteinuria and all-cause mortality in a general population and evaluated the effect of confounders on this association. METHODS:The study population included 17,342,956 adults who underwent health examinations between 2005 and 2008 under the National Health Insurance System. Proteinuria was determined using a single dipstick urinalysis, and the primary outcome of this study was all-cause mortality. The prognostic impact of proteinuria was assessed by constructing a multivariable Cox model. RESULTS:The mean age of the study population (53.24% male) was 46.06 years; 724,681 deaths from all causes occurred over a median follow-up period of 9.34 years (interquartile range 8.17-10.16), and the maximum follow-up was 12.12 years. After full adjustment for covariates, a higher level of dipstick proteinuria indicated a higher risk of all-cause death [Hazard ratios (95% confidence intervals); 1.22 (1.20-1.24), 1.47 (1.45-1.49), 1.81 (1.77-1.84), 2.32 (2.24-2.41), 2.74 (2.54-2.96); trace to 4+, respectively], and various subgroup analyses did not affect the main outcome for the total population. ≥1+ proteinuria in the group without metabolic diseases (hypertension, diabetes, dyslipidemia, or obesity) resulted in higher hazard ratios than those in the group with metabolic diseases and negative or trace proteinuria. CONCLUSIONS:Our study showed a strong association between dipstick proteinuria and all-cause mortality in this nationwide population-based cohort in South Korea.

INTRODUCTION:Despite relevant evidence that supplemental oxygen therapy can be harmful to patients with myocardial injury, the association between hyperoxia and the clinical outcome of such patients has not been evaluated. We assessed whether early hyperoxia negatively affects outcomes in hospitalized patients with myocardial injury. METHODS:This was a retrospective study conducted at a tertiary referral teaching hospital. Between January 2010 and December 2016, 2,376 consecutive emergency department patients with myocardial injury, defined as a peak troponin-I level ≥ 0.2 ng/mL, within the first 24 hours of presentation were included. The metrics used to define hyperoxia were the maximum average partial pressure of oxygen (PaO2MAX), average partial pressure of oxygen (PaO2AVG), and area under the curve during the first 24 hours (AUC24). The association between early hyperoxia within 24 hours after presentation and clinical outcomes was evaluated using multiple imputation and logistic regression analysis. The primary outcome was 28-day in-hospital mortality. The secondary outcomes were new-onset cardiovascular, coagulation, hepatic, renal, and respiratory dysfunctions (sequential organ failure sub-score ≥ 2). RESULTS:Compared with normoxic patients, the adjusted odds ratios (ORs) for PaO2MAX, PaO2AVG, and AUC24 were 1.55 (95% confidence interval (CI) 1.05-2.27; p = 0.026), 2.13 (95% CI 1.45-3.12; p = 0.001), and 1.73 (95% CI 1.15-2.61; p = 0.008), respectively, in patients with mild hyperoxia and 6.01 (95% CI 3.98-9.07; p < 0.001), 8.92 (95% CI 3.33-23.88; p < 0.001), and 7.32 (95% CI 2.72-19.70; p = 0.001), respectively, in patients with severe hyperoxia. The incidence of coagulation and hepatic dysfunction (sequential organ failure sub-score ≥ 2) was significantly higher in the mild and severe hyperoxia group. CONCLUSIONS:Hyperoxia during the first 24 hours of presentation is associated with an increased 28-day in-hospital mortality rate and risks of coagulation and hepatic dysfunction in patients with myocardial injury.

OBJECTIVE:This study was conducted to analyze recent trends of multiple birth rates (MBR) and fetal/neonatal/infant mortalities according to the number of gestations in Korea. METHODS:Data from 2009 to 2015 of live births, infant deaths and stillbirths were obtained from the Korean Vital Statistics. Neonatal mortality rate (NMR), infant mortality rate (IMR), and fetal mortality rate (FMR) in singleton, twin and triplet pregnancies were analyzed according to gestational period (GP; ≤ 23, 24-27, 28-31, and 32-36 weeks). RESULTS:From 2009 to 2015, twin and triplet birth rates increased 34.5% and 154.3%, respectively. In twin births, NMR and FMR have been decreased significantly (from 10.92 to 8.62, p = 0.034 and from 41.00 to 30.55, p< 0.001, respectively), but IMR did not show significant decrease. There was no significant change of NMR, IMR, and FMR, in triplet births. Overall, in singleton, twin, and triplet births, NMR was 1.26 ± 0.09, 10.6 ± 1.12, and 34.32 ± 11.72, respectively, and IMR was 2.38 ± 0.26, 14.52 ± 1.38, and 41.13 ± 12.2, respectively. FMRs were 12 ± 1.73, 35.99 ± 3.55, and 88.85 ± 16.55, respectively, in singleton, twin, and triplet pregnancies. In spite of decreasing trends in overall mortalities, the odds ratios of NMRs and IMRs in 2015 were approximately 9-fold and 6-fold higher, respectively, in twin births, and approximately 37-fold and 20-fold higher, respectively, in triplet births, than those in singleton births. There were no significant differences in odds ratios of NMRs and IMRs at GP 32-36 among single, twin, and triplet births, although the odds ratios of FMR at GP 32-36 in triplet gestation was significantly higher than those in singleton and twin gestation. CONCLUSION:Neonatal/infant mortality in multiple births is still significantly high, which is mainly related with preterm birth. Close fetal monitoring is needed to prevent fetal death in triplet pregnancies, after 32 gestational weeks.

Laparoscopic pylorus-preserving pancreaticoduodenectomy is being performed more frequently because of improved surgical techniques. Although several studies have demonstrated safety and favourable outcomes of laparoscopic pylorus-preserving pancreaticoduodenectomy compared to open pylorus-preserving pancreaticoduodenectomy, few studies have focused on the development of postoperative acute kidney injury. This retrospective study compared the prevalence and risk factors of acute kidney injury following laparoscopic and open pylorus-preserving pancreaticoduodenectomy. Data from 809 patients who underwent pylorus-preserving pancreaticoduodenectomy between February 2012 and September 2016 were analysed. Patients were divided into two groups according to the surgical procedure (open pylorus-preserving pancreaticoduodenectomy [n = 632] vs laparoscopic pylorus-preserving pancreaticoduodenectomy [n = 177]). The Kidney Disease: Improving Global Outcomes criteria were used to define postoperative acute kidney injury and risk factors were investigated using multivariable logistic regression analysis with propensity score matching analysis and standardized mortality ratio weighting to compare outcomes. No significant differences were found in the occurrence of postoperative acute kidney injury and incidence of postoperative ICU admission between open and laparoscopic pylorus-preserving pancreaticoduodenectomy groups after propensity score matching (p = 1.000, p = 0.999, respectivelyand standardized mortality ratio weighted analysis (p = 0.619, p = 0.982, respectively). Hospital stay was significantly shorter in the laparoscopic pylorus-preserving pancreaticoduodenectomy group (propensity matched set, mean [SD], 16.7 [10.0] vs. 18.7 [9.6] days, p = 0.004; standardized mortality ratio, 16.6 [9.9] vs. 18.1 [8.8] days, p = 0.001). There was no significant difference in postoperative acute kidney injury incidence between both groups. Laparoscopic pylorus-preserving pancreaticoduodenectomy is promising with comparable postoperative outcomes to open pylorus-preserving pancreaticoduodenectomy and has the advantage of shorter hospital stay.

Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus.This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase.This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.

Mesenchymal stem cells (MSCs) are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs) and to determine the optimal concentrations of the MSCs in a rabbit model.Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group) were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml). One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically.Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml). Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml) was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml) in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively). The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group.The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair.

The aim of this study was to investigate the association of central and abdominal obesity with the prevalence of cataracts in a middle-aged Korean population. This retrospective cross-sectional study was based on the data collected from the Korea National Health and Nutrition Examination Survey 2008-2009, in which 4,914 subjects were examined. Ophthalmological examinations were performed to determine the presence of a nuclear, cortical, or posterior subcapsular cataract. Both general obesity (a body mass index ≥25 kg/m2) and abdominal obesity (a waist circumference ≥90 cm for men and ≥80 cm for women) were significantly associated with the occurrence of cataracts among middle-aged women [adjusted odds ratio (aOR), 1.32; 95% confidence interval (CI), 1.03-1.69; and aOR, 1.40; 95% CI, 1.06-1.85, respectively], while abdominal obesity was significantly inversely associated with the occurrence of cataracts among middle-aged men (aOR, 0.76; 95% CI, 0.58-1.01; and aOR, 0.66; 95% CI, 0.49-0.89, respectively). We report a difference in the association between obesity and the prevalence of cataracts based on gender.

Based on reports of an association between elevated intraocular pressure (IOP) and metabolic syndrome (MetS), and the major role of insulin resistance (IR) in MetS pathogenesis, a positive association between IOP and IR has been hypothesized. Although Asian populations tend to have lower body mass indices (BMIs) than Western populations, they tend to have a higher risk of developing MetS. This study examined the hypothesis that the association between IOP and IR differs by obesity status in an Asian population, by examining a nationally representative sample of South Korean adults. Data collected from 4,621 South Korean adults regarding demographic, lifestyle, and laboratory parameters by the 2010 Korea National Health and Nutrition Examination Survey were subjected to linear regression analysis to evaluate the relationship between IOP and metabolic profiles. After adjusting for confounding factors, the data were subjected to multiple linear regression analysis to examine the association between IR, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR), and IOP. Obesity was defined as BMI≥27.5 kg/m2, and the subjects were divided into obese vs. non-obese groups for investigation of the association between IR and IOP according to obesity status. IOP was found to correlate with fasting blood sugar, total cholesterol, insulin, and HOMA-IR values in non-obese men; and with BMI, waist circumference, triglycerides, total cholesterol, HOMA-IR, and low-density lipoprotein cholesterol values in non-obese women, whereas no association between IOP and IR was found in obese men or women. IOP was significantly associated with IR in non-obese men and women after adjusting for age, and in non-obese men after adjusting for age, BMI, and lifestyle and demographic factors. These findings indicate that a positive and independent relationship exists between IOP and IR in non-obese individuals only, suggesting that other factors likely contribute to IOP elevation in obese individuals.

BACKGROUND:To investigate the effects of age and sex on the relationship between socioeconomic status (SES) and the prevalence and control status of diabetes mellitus (DM) in Korean adults. METHODS:Data came from 16,175 adults (6,951 men and 9,227 women) over the age of 30 who participated in the 2008-2010 Korea National Health and Nutrition Examination Survey. SES was measured by household income or education level. The adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) for the prevalence or control status of diabetes were calculated using multiple logistic regression analyses across household income quartiles and education levels. RESULTS:The household income-DM and education level-DM relationships were significant in younger age groups for both men and women. The adjusted ORs and 95% CI for diabetes were 1.51 (0.97, 2.34) and 2.28 (1.29, 4.02) for the lowest vs. highest quartiles of household income and education level, respectively, in women younger than 65 years of age (both P for linear trend < 0.05 with Bonferroni adjustment). The adjusted OR and 95% CI for diabetes was 2.28 (1.53, 3.39) for the lowest vs. highest quartile of household income in men younger than 65 (P for linear trend < 0.05 with Bonferroni adjustment). However, in men and women older than 65, no associations were found between SES and the prevalence of DM. No significant association between SES and the status of glycemic control was detected. CONCLUSIONS:We found age- and sex-specific differences in the relationship of household income and education with the prevalence of DM in Korea. DM preventive care is needed for groups with a low SES, particularly in young or middle-aged populations.

Severe xerostomia (dry mouth) compromises the quality of life in patients with Sjögren's syndrome or radiation therapy for head and neck cancer. A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utilizing high-throughput iTRAQ-2D-LC-MS/MS-based proteomics. Our data revealed the novel induction of pancreas-specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1), and achaete-scute complex homolog 3 (ASCL3) in 7 day co-cultured MSCs but not in control MSCs. More importantly, a common notion of pancreatic-specific expression of PTF1 α was challenged for the first time by our verification of PTF1 α expression in the mouse salivary glands. Furthermore, a molecular network simulation of our selected putative MSC reprogramming factors demonstrated evidence for their perspective roles in salivary gland development. In conclusion, quantitative proteomics with extensive data analyses narrowed down a set of MSC reprograming factors potentially contributing to salivary gland regeneration. Identification of their differential/synergistic impact on MSC conversion warrants further investigation.

BACKGROUND:The placenta is a very attractive source of mesenchymal stem cells (MSCs) for regenerative medicine due to readily availability, non-invasive acquisition, and avoidance of ethical issues. Isolating MSCs from parts of placenta tissue has obtained growing interest because they are assumed to exhibit different proliferation and differentiation potentials due to complex structures and functions of the placenta. The objective of this study was to isolate MSCs from different parts of the placenta and compare their characteristics. METHODS:Placenta was divided into amniotic epithelium (AE), amniotic membrane (AM), chorionic membrane (CM), chorionic villi (CV), chorionic trophoblast without villi (CT-V), decidua (DC), and whole placenta (Pla). Cells isolated from each layer were subjected to analyses for their morphology, proliferation ability, surface markers, and multi-lineage differentiation potential. MSCs were isolated from all placental layers and their characteristics were compared. FINDINGS:Surface antigen phenotype, morphology, and differentiation characteristics of cells from all layers indicated that they exhibited properties of MSCs. MSCs from different placental layers had different proliferation rates and differentiation potentials. MSCs from CM, CT-V, CV, and DC had better population doubling time and multi-lineage differentiation potentials compared to those from other layers. CONCLUSIONS:Our results indicate that MSCs with different characteristics can be isolated from all layers of term placenta. These finding suggest that it is necessary to appropriately select MSCs from different placental layers for successful and consistent outcomes in clinical applications.

Cytomegaloviruses (CMV) can have a significant impact on the prognosis of immunocompromised patients. Unlike in the transplantation and AIDS fields, only a few studies on CMV infections have been published in the field of autoimmunity. In this study, we examined the clinical outcomes of CMV infections in patients with autoimmune diseases at a single tertiary medical institution.A retrospective study was performed to identify the mortality risk factors associated with CMV infections in patients with autoimmune diseases. We reviewed the medical records of patients with autoimmune diseases who were diagnosed with CMV infections using real-time quantitative polymerase chain reaction between December 2005 and March 2016. Clinical and laboratory parameters as well as treatment outcomes were analyzed.Seventy-three CMV infected patients were separated into survivors and non-survivors. Non-survivors had significantly higher median CMV-DNA copy numbers than survivors (95,500 vs 6,700 copies/mL, p = 0.005) and demonstrated significantly more frequent incidents of CMV pneumonitis (69.2 vs 36.2%, p = 0.007). After adjusting for multiple confounding covariates, the log CMV-DNA copies/mL (hazard ratio, 1.48; 95% confidence interval, 1.14-1.92; p = 0.003) and the presence of concurrent infections (hazard ratio, 22.00; 95% confidence interval, 2.75-175.97, p = 0.004) were identified as independent mortality risk factors. Furthermore, patients with high CMV copy numbers (> 60,000 copies/mL) had higher in-hospital mortality than those with low CMV copy numbers (p < 0.05).CMV-DNA copy numbers and concurrent infections are predictors of in-hospital mortality in CMV-infected patients with autoimmune diseases. Therefore, serial measurements of CMV-DNA copy numbers and close observation for signs of other infections are recommended for patients with autoimmune diseases who have concurrent CMV infection.

We aimed to evaluate a wide spectrum of clinical features of adult patients with spondyloarthritis (SpA) whose initial manifestation was fever, using the Assessment of SpondyloArthritis international Society (ASAS) classification criteria.We retrospectively collected the electronic medical records of hospitalized SpA patients who initially presented to the Severance Hospital (Seoul, Korea) with fever from January 2010 to May 2016. As a control group, we also recruited one-hundred consecutive patients who were diagnosed with SpA in our outpatient clinic. Clinical features and laboratory findings were compared in two patient groups.There were 26 patients who had fever as initial presentation of SpA (reactive arthritis 50%, undifferentiated SpA 26.9%, ankylosing spondylitis 15.4%, enteropathic arthritis 3.8%, psoriatic arthritis 3.8%). Peripheral SpA was more common in febrile SpA patients than in control SpA patients (65.4% vs 24.0%, p

BACKGROUND:Histological chorioamnionitis (HCA) is related to perinatal morbidity. However, there is no definite diagnostic method for detecting chorioamnionitis before delivery. METHODS:We evaluated whether the delta neutrophil index (DNI) was an effective early marker of HCA in patients with preterm premature rupture of membranes (PPROM). We retrospectively evaluated 149 women diagnosed with PPROM (gestational age, 20+0 to 36+6 weeks) at Severance Hospital from January 2013 to December 2014. The women were categorized into the following two groups: (a) PPROM without HCA and (b) PPROM with HCA. The maternal white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) level, and DNI were measured at admission. The DNI has been reported to reflect the fraction of circulating immature granulocytes associated with infection. RESULTS:Of the 149 patients, 87 were included in the PPROM without HCA group and 62 were included in the PPROM with HCA group. The interval between admission and delivery was significantly shorter in the PPROM with HCA group than in the PPROM without HCA group. There was no significant difference in the maternal WBC count. The serum CRP level, NLR, and DNI were significantly lower in the PPROM without HCA group than in the PPROM with HCA group, while the lymphocyte count was significantly lower in the PPROM with HCA group than in the PPROM without HCA group. A predictive equation was generated by combining the DNI, lymphocyte count, and CRP level, and the sensitivity and specificity for predicting a placental inflammatory response were 69.1% and 70.5%, respectively. CONCLUSIONS:The DNI could be a predictive marker for HCA in patients with PPROM. Our predictive equation involving the DNI, lymphocyte count, and CRP level may be helpful for predicting the placental inflammatory response in patients with PPROM.

Despite recent advances in methods for culturing Mycobacterium tuberculosis (MTB), the diagnostic yield of tuberculous pleural effusion (TBPE) remains unsatisfactory. However, unlike repeated sputum cultures of pulmonary tuberculosis, little is known about the role of repeated pleural cultures. We examined whether repeated pleural cultures are associated with increased MTB yield from TBPE.A multicenter, retrospective cohort study was performed from January 2012 to December 2015 in South Korea. Patients were categorized into two groups: single- or repeated-culture groups. The diagnostic yield of MTB and clinical, radiological, and pleural fluid characteristics were evaluated.Among the 329 patients with TBPE, 77 (23.4%) had repeated cultures and 252 (76.5%) had a single culture. Pleural culture was performed twice in all 77 patients in the repeated-culture group at a 1-day interval (inter-quartile range, 1.0-2.0). In the repeated-culture group, the yield of MTB from the first culture was 31.2%, which was similar to that in the single-culture group (31.2% vs. 29.8%, P = 0.887). However, the yield of MTB from the second culture (10/77, 13.0%) was more than that from the first. These results may be attributable to the insufficient immune clearance for MTB invasion into the pleural space between the first and second cultures. Over time, the yield of the second cultures decreased from 17.4% to 6.7% and then 6.3%. Finally, the overall yield of MTB in the repeated- and single-culture groups was 44.2% and 29.8% respectively (P < 0.001).The results showed that repeated pleural cultures increased MTB yield from TBPE in human immunodeficiency virus-negative individuals. Furthermore, repeated cultures may increase yield when carried out for two consecutive days.

We conducted a systematic review and meta-analysis of studies to quantify the association between body mass index (BMI) and the risks of all-cause and cardiovascular mortality in patients with type 2 diabetes.We included studies assessing the impact of BMI on all-cause and cardiovascular mortality in patients with type 2 diabetes. Data were combined using a random-effects dose-response model.Sixteen cohort studies on all-cause mortality (n = 445,125) and two studies on cardiovascular mortality (n = 92,841) were evaluated in the meta-analysis. A non-linear association was observed between BMI and all-cause mortality among patients with type 2 diabetes. With a BMI nadir of 28-30 kg/m2, the risk of all-cause mortality displayed a U-shaped increase. With a BMI nadir of 29-31 kg/m2, the risk of cardiovascular mortality exhibited a gradual non-linear increase for BMI > 31 kg/m2. Subgroup analyses suggested that study location, diabetes duration, and smoking history may have contributed to heterogeneity among the studies.An obesity paradox exists for patients with type 2 diabetes with respect to all-cause and cardiovascular mortality. Study location, diabetes duration, and smoking history might contribute to heterogeneity among obesity paradox studies of patients with type 2 diabetes.