Background: We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians. Methods: We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hoursight, >5 to 7 hoursight (reference), and >7 hoursight. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex. Results: During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 hight had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hoursight group in non-obese individuals, men, and those aged <60 years, and in the >7 hoursight group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively). Conclusion This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.

Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.

Objective: Recently, microRNA (miRNA) has been identified both as a powerful regulator involved in various biological processes through the regulation of numerous genes and as an effective biomarker for the prediction and diagnosis of various disease states. The objective of this study was to identify and validate miRNAs and their target genes involved in inflammation in placental tissue. Methods: Microarrays were utilized to obtain miRNA and gene expression profiles from placentas with or without inflammation obtained from nine normal pregnant women and 10 preterm labor patients. Quantitative real-time polymerase chain reaction and Western blots were performed to validate the miRNAs and differentially-expressed genes in the placentas with inflammation. Correlations between miRNA and target gene expression were confirmed by luciferase assays in HTR-8/SVneo cells. Results: We identified and validated miRNAs and their target genes that were differentially expressed in placentas with inflammation. We also demonstrated that several miRNAs (miR-371a-5p, miR-3065-3p, miR-519b-3p, and miR-373-3p) directly targeted their target genes (LEF1, LOX, ITGB4, and CD44). However, some miRNAs and their direct target genes showed no correlation in tissue samples. Interestingly, miR-373-3p and miR-3065-3p were markedly regulated by lipopolysaccharide (LPS) treatment, although the expression of their direct targets CD44 and LOX was not altered by LPS treatment. Conclusion These results provide candidate miRNAs and their target genes that could be used as placental biomarkers of inflammation. These candidates may be useful for further miRNA-based biomarker development.

Background: This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs). Methods: In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed. Results: Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators’ assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients’ LDL-C levels was the primary reason for non-intensification of statin therapy. Conclusion Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

OBJECTIVE: The Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) aimed to recruit 650 individuals, aged from 20 to 90 years, to search for new biomarkers of Alzheimer's disease (AD) and to investigate how multi-faceted lifetime experiences and bodily changes contribute to the brain changes or brain pathologies related to the AD process. METHODS: All participants received comprehensive clinical and neuropsychological evaluations, multi-modal brain imaging, including magnetic resonance imaging, magnetic resonance angiography, [11C]Pittsburgh compound B-positron emission tomography (PET), and [18F]fluorodeoxyglucose-PET, blood and genetic marker analyses at baseline, and a subset of participants underwent actigraph monitoring and completed a sleep diary. Participants are to be followed annually with clinical and neuropsychological assessments, and biannually with the full KBASE assessment, including neuroimaging and laboratory tests. RESULTS: As of March 2017, in total, 758 individuals had volunteered for this study. Among them, in total, 591 participants–291 cognitively normal (CN) old-aged individuals, 74 CN young- and middle-aged individuals, 139 individuals with mild cognitive impairment (MCI), and 87 individuals with AD dementia (ADD)–were enrolled at baseline, after excluding 162 individuals. A subset of participants (n=275) underwent actigraph monitoring. CONCLUSION: The KBASE cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (CN, MCI, and ADD) and it has several strengths in its design and methodologies. Details of the recruitment, study methodology, and baseline sample characteristics are described in this paper.
Aging* ; Alzheimer Disease* ; Biomarkers ; Brain* ; Cohort Studies ; Dementia ; Early Diagnosis* ; Genetic Markers ; Magnetic Resonance Angiography ; Magnetic Resonance Imaging ; Mild Cognitive Impairment ; Neuroimaging ; Pathology ; Prospective Studies

Hepatocellular carcinomas (HCCs) in patients with Crohn's disease (CD) without underlying chronic hepatitis or liver cirrhosis are extremely rare. Previously reported cases occurred in patients who had developed CD at a young age and had been treated with immunosuppressive agents long-term. We herein report the first case of HCC in a 34-year-old patient with CD in Korea. The patient was treated with azathioprine for 14 years and had undergone repeated surgeries for CD. During the follow-up period, the patient was hospitalized for colon perforation and pericolic abscess formation. Computed tomography showed a liver mass, and HCC was diagnosed based on liver biopsy. The patient underwent right hemicolectomy for colon perforation and transcatheter arterial chemoembolization followed by radiofrequency ablation for the HCC. The present case is similar to previously reported cases with the exception of the liver pathology findings, which exhibited neither primary sclerosing cholangitis nor focal hepatic glycogenolysis.
Abscess ; Adult ; Azathioprine ; Biopsy ; Carcinoma, Hepatocellular* ; Catheter Ablation ; Cholangitis, Sclerosing ; Colon ; Crohn Disease* ; Follow-Up Studies ; Glycogenolysis ; Hepatitis, Chronic ; Humans ; Immunosuppressive Agents ; Korea ; Liver ; Liver Cirrhosis ; Pathology ; Infliximab

BACKGROUND/AIMS: The aim of this study was to examine the distribution of range of liver enzymes according to age and BMI in each gender using large-scale data. METHODS: Data were gathered from 65,715 subjects who underwent a routine health check-up and did not have HBsAg and anti-HCV. Boxplot analysis was used to examine the distribution of range of liver enzymes according to age and BMI in each gender. Multivariate linear regression analysis was performed for assessment of the association of liver enzymes with age and BMI, and to determine whether the range of liver enzymes was affected by risk factors for metabolic syndrome in each gender. RESULTS: ALT, AST, and GGT levels showed significant association with BMI in both male and female after adjusting for age. The range of ALT, AST, and GGT levels varied more widely according to the increase in BMI in males than in females, and this finding was more prominent in younger subjects than in older subjects. All risk factors for metabolic syndrome were shown to affect liver enzyme levels in male subjects. However, although most risk factors for metabolic syndrome affected liver enzyme levels, there might be weak or no effect of fasting hyperglycemia on AST, and low serum HDL-cholesterol level on GGT in female subjects. CONCLUSIONS: Age, BMI, and other risk factors for metabolic syndrome had a significant effect on the distribution of range of liver enzymes in each gender, even in this study conducted from Korean health checkup subjects.
Alanine Transaminase ; Aspartate Aminotransferases ; Body Mass Index* ; Fasting ; Female ; Hepatitis B Surface Antigens ; Humans ; Hyperglycemia ; Linear Models ; Liver* ; Male ; Metabolic Syndrome X ; Risk Factors

Aortic stenosis is the most frequent type of valvular heart disease in adult. Approximately 2-7% of the population over the age of 65 suffer from aortic valve stenosis. Due to the increasing average life expectancy in Korea, degenerative aortic stenosis is increasing and becoming a troublesome health problem in older population. Because older patients with severe degenerative aortic stenosis have many other medical conditions so they are not suitable candidate for surgery. Recently, transcatheter aortic-valve implantation (TAVI) has been suggested as a less invasive treatment for patients with high perioperative risk. We report a successful TAVI case in severe aortic stenosis patient with high perioperative risk.
Adult ; Aortic Valve Stenosis ; Heart Valve Diseases ; Humans ; Korea ; Life Expectancy

BACKGROUND/AIMS: Intestinal metaplasia (IM) has been regarded as a premalignant condition. This study evaluated the role of the transforming factor CDX2 according to the severity and type of IM. METHODS: This analysis was performed on 383 subjects with IM in the antrum and/or body, with diagnoses that were categorized as controls, dysplasias, and gastric cancers. The IM grades were classified into four groups as negative, mild, moderate or severe using the updated Sydney scoring system. The IM subtypes were categorized as type I, type II, and type III using high iron diamine and alcian blue (pH 2.5) staining. The CDX2 expression in the IM foci was evaluated using immunohistochemistry in specimens from the antrum and/or body. RESULTS: CDX2 expression increased according to IM severity (p=0.001) but was not associated with the IM subtype (p=0.881) in the antrum specimens. Similarly, CDX2 expression increased according to the IM grade (p=0.001) but was not associated with the IM subtype (p=0.755) in the body specimens. CDX2 expression was also increased according to baseline disease in the antrum, especially dysplastic and GC group (p=0.003), but not in the body (p=0.582). However, status of Helicobacter pylori infection was not associated with CDX2 expression in the antrum (p=0.692) and body (p=0.271). CONCLUSIONS: These results show that CDX2 expression is associated with the IM grade regardless of the IM subtype and that it was more frequent in the dysplasia group. These results suggest that CDX2 expression might play an important role in the progression of IM in various environments that can affect neoplastic change.
Alcian Blue ; Helicobacter pylori ; Immunohistochemistry ; Iron ; Metaplasia ; Stomach Neoplasms

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.
Aged ; Female ; Helicobacter Infections/complications/microbiology ; Helicobacter pylori/isolation & purification ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Intestinal Diseases/*genetics/microbiology/pathology ; Male ; Metaplasia/pathology ; Middle Aged ; Polymerase Chain Reaction ; Precancerous Conditions/metabolism/pathology ; Stomach Neoplasms/etiology/*genetics/microbiology