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Background: Hyperbaric oxygen (HBO2) therapy is a safe and well-tolerated treatment modality. Seizures, one of the most severe central nervous system side effects of HBO2 therapy, can occur. Episodes of seizures during HBO2 therapy have not yet been reported in countries such as Korea, where hyperbaric medicine is still in the developmental stage. Methods: The registry data of all patients treated with HBO2 therapy in a tertiary academic hospital in Korea were prospectively collected, and patients who developed seizures during HBO2 therapy between October 2016 and December 2019 were evaluated. In addition, we reviewed previous studies on occurrence of seizures during HBO2 therapy. Results: During the study period, a total of 10,425 treatments were provided to 1,308 patients. The most frequently treated indication was carbon monoxide (CO) poisoning (n=547, 41.8%). During the HBO2 therapy sessions (total: 10,425), five seizure episodes occurred (patients with CO poisoning: n=4; patients with arterial gas embolism [AGE]: n=1). The frequency of seizures in patients with CO poisoning (0.148%) and AGE (3.448%) was significantly higher than that in patients with all indications (0.048%) (p=0.001). None of the patients had lasting effects due to the seizures. Conclusion: Our study revealed a similar frequency rate in terms of all indications and CO poisoning, and a slightly higher rate in AGE. Seizures were observed in patients with CO poisoning and AGE. Therefore, if clinicians plan to operate a hyperbaric center in a country like Korea, where there are several patients with acute CO poisoning, they should be prepared to handle seizures that may occur during HBO2 therapy

Objective. Although gout is the most common form of inflammatory arthritis, data on gout prevalence and management are sparse, especially in Korean populations. This study reevaluated the most recent prevalence and incidence of gout values in Korean people to update the findings from our previous study in 2011. Methods. We used the National Health Insurance Service-National Health Information Database (NHIS-NHID) to identify patients diagnosed with gout in South Korea during 2002∼2015. We selected patients with gout as principal diagnosis or 1st∼4th additional diagnosis. Results. The prevalence of gout increased 5.17-fold, from 0.39% in 2002 to 2.01% in 2015. This increase occurred in all age groups, but was stronger in those aged 80 years or older, with a 13.1-fold increase from 2002 to 2015. The prevalence of gout increased in all regions of South Korea. The prevalence of the disease was also related to income levels: in 2015, medical insurance subscribers with the highest income were twice more likely to have gout than those in the lowest income bracket. By contrast, the prevalence of gout in medical benefit recipients was 5.58- and 5.25-times higher than that of the general population and of those in the highest income bracket, respectively. Conclusion. The prevalence of gout has increased rapidly, although the degree of increase varied according to sex, age, region, and income group. This study sheds some light on the current prevalence of gout among national insurance subscribers in Korea, and will help educate patients and medical staff on the management of gout. (J Rheum Dis 2020;27:174-181)

This study aimed to determine the impact of dysglycemia on myocardial injury and cardiac dysfunction in acute myocardial in farctions (AMIs). From 2005 to 2016, a total of 1,593 patients with AMIs who underwent percutaneous coronary intervention were enrolled. The patients were classified into five groups according to the admission glucose level: ≤80, 81 to 140, 141 to 200, 201 to 260, and ≥261 mg/dL. The clinical and echocardiographic parameters and 30-day mortality were analyzed. The peak tro ponin I and white blood cell levels had a positive linear relationship to the admission glucose level. The left ventricular ejection fraction had an inverted U-shape trend, and the E/E’ ratio was U-shaped based on euglycemia. The 30-day mortality also in creased as the admission glucose increased, and the cut-off value for predicting the mortality was 202.5 mg/dL. Dysglycemia, es pecially hyperglycemia, appears to be associated with myocardial injury and could be another adjunctive parameter for predicting mortality in patients with AMIs.

Objective: The purposes of this study was to evaluate the diagnostic values of abdominal muscles thickness and sterno-costal angle as the quantitative...

Background Obese mice on a high-fat diet (HFD) display signs of inflammation in the hypothalamic arcuate nucleus (ARC), a critical area for controlling systemic energy metabolism. This has been suggested as a key mechanism of obesity-associated hypothalamic dysfunction. We reported earlier that bone marrow-derived macrophages accumulate in the ARC to sustain hypothalamic inflammation upon chronic exposure to an HFD. However, the mechanism underlying hypothalamic macrophage accumulation has remained unclear. Methods We investigated whether circulating monocytes or myeloid precursors contribute to hypothalamic macrophage expansion during chronic HFD feeding. To trace circulating myeloid cells, we generated mice that express green fluorescent protein (GFP) in their lysozyme M-expressing myeloid cells (LysMGFP mice). We conducted parabiosis and bone marrow transplantation experiments using these animals. Mice received an HFD for 12 or 30 weeks and were then sacrificed to analyze LysMGFP cells in the hypothalamus. Hypothalamic vascular permeability in the HFD-fed obese mice was also tested by examining the extravascular leakage of Evans blue and fluorescence-labeled albumin. The timing of LysMGFP cell entry to the hypothalamus during development was also evaluated. Results Our parabiosis and bone marrow transplantation experiments revealed a significant infiltration of circulating LysMGFP cells into the liver, skeletal muscle, choroid plexus, and leptomeninges but not in the hypothalamic ARC during chronic HFD feeding, despite increased hypothalamic vascular permeability. These results suggested that the recruitment of circulating monocytes is not a major mechanism for maintaining and expanding the hypothalamic macrophage population in diet-induced obesity. We demonstrated instead that LysMGFP cells infiltrate the hypothalamus during its development. LysMGFP cells appeared in the hypothalamic area from the late embryonic period. This cellular pool suddenly increased immediately after birth, peaked at the postnatal second week, and adopted an adult pattern of distribution after weaning. Conclusions Bone marrow-derived macrophages mostly populate the hypothalamus in early postnatal life and may maintain their pool without significant recruitment of circulating monocytes throughout life, even under conditions of chronic HFD feeding.

BACKGROUND AND OBJECTIVES The relationship between operator volume and outcomes of percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) has not been fully investigated. We aimed to investigate the relationship between operator PCI volume and in-hospital outcomes after primary PCI for STEMI. METHODS Among the total of 44,967 consecutive cases of PCI enrolled in the Korean nationwide, retrospective registry (K-PCI registry), 8,282 patients treated with PCI for STEMI by 373 operators were analyzed. PCI volumes above the 75th percentile (>30 cases/year), between the 75th and 25th percentile (10-30 cases/year), and below the 25th percentile (

Background: There is controversy regarding the long-term effect of glycemic control on the clinical outcomes after percutaneous coronary intervention (PCI) in diabetes patients with coronary artery disease (CAD). We aimed to evaluate the long-term outcomes of patients with diabetes who underwent PCI, according to the mean hemoglobin A1c (HbA1c) level after PCI.Methods: We retrospectively evaluated 675 diabetes patients with CAD treated with PCI from 2010 to 2013. We categorized the study population into three groups based on the mean observed HbA1c levels during the follow-up duration, as follows: aggressive control (AC) group (HbA1c level Results: The mean HbA1c level of the AC group was significantly lower than that of the MC and UC groups (6.04±0.36% vs. 6.74±0.14% vs. 8.39±1.20%, pConclusion: Our study showed that intensive glycemic control (HbA1c level

Mutations that inactivate negative translation regulators cause autism spectrum disorders (ASD), which predominantly affect males and exhibit social interaction and communication deficits and repetitive behaviors. However, the cells that cause ASD through elevated protein synthesis resulting from these mutations remain unknown. Here we employ conditional overexpression of translation initiation factor eIF4E to increase protein synthesis in specific brain cells. We show that exaggerated translation in microglia, but not neurons or astrocytes, leads to autism-like behaviors in male mice. Although microglial eIF4E overexpression elevates translation in both sexes, it only increases microglial density and size in males, accompanied by microglial shift from homeostatic to a functional state with enhanced phagocytic capacity but reduced motility and synapse engulfment. Consequently, cortical neurons in the mice have higher synapse density, neuroligins, and excitation-to-inhibition ratio compared to control mice. We propose that functional perturbation of male microglia is an important cause for sex-biased ASD., The main cell types involved in autism spectrum disorders through elevated protein synthesis are not well identified. Here, the authors show that overexpression of translation initiation factor eIF4E in microglia results in autism-like behaviour in male, but not female, mice.

Background Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention. Methods Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138). Results During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%, P = 0.118). However, appropriate ICD therapy rate including shock and anti-tachycardia pacing was significantly higher (primary 18% vs. secondary 34.8%, P = 0.001) in the secondary prevention group. Type of prevention and etiology, appropriate and inappropriate ICD shock did not affect all-cause death. High levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association functional class, low levels of estimated glomerular filtration ratio, and body mass index were associated with death before appropriate ICD shock in the primary prevention group. When patients were categorized in 5 risk score groups according to the sum of values defined by each cut-off level, significant differences in death rate before appropriate ICD shock were observed among risk 0 (0%), 1 (3.6%), 2 (3%), 3 (26.5%), and 4 (40%) (P < 0.001). Conclusion In this multicenter regional registry, the frequency of appropriate ICD therapy is not low in the primary prevention group. In addition, combination of poor prognostic factors of heart failure is useful in risk stratification of patients who are not benefiting from ICD therapy for primary prevention., Graphical Abstract

Background Multicentric carpotarsal osteolysis syndrome (MCTO) is characterized by progressive destruction and disappearance of the carpal and tarsal bones associated with nephropathy. MCTO is caused by loss-of-function mutations in the MAF bZIP transcription factor B (MAFB) gene. Case presentation This report describes three unrelated patients with MAFB mutations, including two male and one female patient. Osteolytic lesions in the carpal and tarsal bones were detected at 2 years, 12 years, and 14 months of age, respectively. Associated proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively. Kidney biopsy was performed in two of them and revealed focal segmental glomerulosclerosis (FSGS). One patient showed progression to end-stage renal disease, that is by 1 year after the detection of proteinuria. The second patient had persistent proteinuria but maintained normal renal function. In the third patient, who did not undergo a kidney biopsy, the proteinuria disappeared spontaneously. The bony lesions worsened progressively in all three patients. Mutational study of MAFB revealed three different mutations, two novel mutations [c.183C > A (p.Ser61Arg) and c.211C > G (p.Pro71Ala)] and one known mutation [c.212C > T (p.Pro71Leu)]. Conclusion We report three cases with MCTO and two novel MAFB mutations. The renal phenotypes were different among the three patients, whereas progressive worsening of the bony lesions was common in all patients. We also confirmed FSGS to be an early renal pathologic finding in two cases. A diagnosis of MCTO should be considered in patients with progressive bone loss concentrated primarily in the carpal and tarsal bones and kidney involvement, such as proteinuria.

Context.— Anticyclic citrullinated peptide antibodies are important serologic markers for the diagnosis of rheumatoid arthritis. Several kinds of test reagents for automated immunoassay systems have been developed and used in recent years. Objective.— To evaluate the analytic and diagnostic performance of the new ADVIA Centaur anticyclic citrullinated peptide assay (Siemens Healthineers, Erlangen, Germany) compared with the Elecsys assay (Roche Diagnostics, Mannheim, Germany). Design.— A total of 576 serum samples were collected from subjects, including 156 patients (27%) with rheumatoid arthritis. Precision performance and analytical measurement range for the ADVIA assay were evaluated. Diagnostic performance of the 2 assays was compared based on sensitivity, specificity, and area under the receiver operating characteristic curves. Results.— The ADVIA assay showed a within-laboratory imprecision of 3.4% coefficient of variation for levels of 3.36 and 24.99 U/mL. This assay was demonstrated to be linear from 0.4 to 180.0 U/mL. With default cutoff values, sensitivity and specificity for diagnosing rheumatoid arthritis were 71.2% and 97.9%, respectively, for the ADVIA assay and 73.1% and 96.9%, respectively, for the Elecsys assay. With the best cutoff values from the analyses of the receiver operating characteristic curve, the sensitivity of the 2 assays was the same at 75.6%. However, the specificity of the ADVIA assay was 96.4%, whereas that of the Elecsys assay was 94.3%. The area under the receiver operating characteristic curve value for the ADVIA assay was 0.867, which was not significantly different from that of the Elecsys assay (0.865). Conclusions.— The ADVIA Centaur anticyclic citrullinated peptide assay showed good analytic and diagnostic performance in diagnosing rheumatoid arthritis.

The clinical impact of body mass index (BMI), especially in the elderly with acute myocardial infarction (AMI), has not been sufficiently evaluated. The purpose of this study was to elucidate the clinical impact of BMI in very old patients (≥80 years) with AMI.The study analysed 2,489 AMI patients aged ≥80 years from the Korea Acute Myocardial Infarction Registry and the Korea Working Group on Myocardial Infarction (KAMIR/KorMI) registries between November 2005 and March 2012. The study population was categorised into four groups based on their BMI: underweight (n=301), normal weight (n=1,150), overweight (n=890), and obese (n=148). The primary endpoint was major adverse cardiovascular event (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularisation, and target vessel revascularisation.Baseline characteristics among the four groups were similar, except for hypertension (45.1 vs 58.4 vs 66.2 vs 69.9%, respectively; p0.001) and diabetes (16.6 vs 23.6 vs 30.7 vs 35.1%, respectively; p0.001). Coronary care unit length of stay was significantly different among the four groups during hospitalisation (5.3±5.9 vs 4.8±6.8 vs 4.2±4.0 vs 3.5±2.1 days; p=0.007). MACE (16.9 vs 14.9 vs 13.7 vs 8.8%; p=0.115) and cardiac death (10.3 vs 8.4 vs 7.9 vs 4.1%; p=0.043) less frequently occurred in the obese group than in other groups during the 1-year follow-up. A multivariate regression model showed obese status (BMI ≥27.5 kg/mBody mass index in elderly patients with acute myocardial infarction was significantly associated with coronary care unit stay and clinical cardiovascular outcomes.

Licensed live attenuated vaccines have been developed to prevent varicella zoster virus (VZV) infection, which causes chickenpox and shingles. The genomic sequences of both clinical- and vaccine-derived VZV strains have been analyzed previously. To further characterize the molecular signatures and complexity of wildtype (clinical) versus attenuated (vaccine-derived) VZV-mediated host cellular responses, we performed high-throughput next generation sequencing to quantify and compare the expression patterns of mRNAs and microRNAs (miRNAs) in primary human dermal fibroblasts (HDFs) infected with wildtype (YC01 low passage) and attenuated (YC01 high passage, SuduVax, and VarilRix) VZV strains. 3D-multidimensional scaling of the differentially expressed genes demonstrated the distinct grouping of wildtype and attenuated strains. In particular, we observed that HDFs infected with attenuated strains had more differentially expressed genes (DEGs) involved in the retinoic-acid inducible gene&ndash, I-like receptor and interferon-mediated signaling pathways compared with wildtype strains. Additionally, miRNA expression patterns were profiled following the infection of HDFs with VZV. Small RNA sequencing identified that several miRNAs were upregulated, including miR-146a-5p, which has been associated with other herpesvirus infections, whereas let-7a-3p was downregulated in both wildtype and attenuated VZV-infected cells. This study identified genes and miRNAs that may be essential in VZV pathogenesis.

Purulent pericarditis is defined as a localized pericardial infection with gross pus formation in the pericardial space. Although purulent pericarditis is now rare in the antibiotic era, it may be life-threatening. We describe a rare case of purulent pericarditis that originated from a subdiaphragmatic suppurative focus in an immunocompromised host.

A recent guideline emphasized strict blood pressure (BP) control for the patients at high risk for cardiovascular events. However, there are little data about the relationship between BP control and clinical outcome in Korea. We sought to evaluate the clinical outcomes according to the mean observed BP in patients with coronary artery disease (CAD) who had undergone drug-eluting stent (DES) implantation.We reviewed records of 1010 CAD patients with DES from 2010 through 2011. After excluding in-hospital mortality cases (n = 79), we categorized patients into two groups based on the average SBP (SBP) at the outpatient clinic: mean SBP 120 mmHg or less (n = 290) and mean SBP greater than 120 mmHg (n = 641). Primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as cardiac death, myocardial infarction, repeat target vessel revascularization, or stroke. Propensity score matching was performed to adjust for differences in baseline clinical variables. Median follow-up duration was 77.7 (36.6-87.3) months.The mean SBP greater than 120 mmHg had higher prevalence of cardiovascular risk factors, such as diabetes (38.4 vs. 27.2%, P = 0.001), hypertension (58.8 vs. 32.4%, P 0.001), and chronic kidney disease (3.3 vs. 1.0%, P = 0.043) than mean SBP 120 mmHg or less. MACCE incidence was significantly lower in the mean SBP 120 mmHg or less than in the mean SBP greater than 120 mmHg (14.3 vs. 22.0%, P = 0.007) at 77.7 months. Even after propensity score matching, the mean SBP 120 mmHg or less showed significantly reduced MACCE rate (14.3 vs. 22.8%, P = 0.007).Mean observed SBP 120 mmHg or less was associated with a lower incidence of future adverse outcomes in CAD patients with DES.

A 73-year-old woman was referred to the pulmonology department for abnormal findings on chest computed tomography. She had undergone a laparoscopic staging operation including a hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic node and para-aortic node dissection, and concurrent chemo-radiation therapy for endometrial serous carcinoma stage IIIc cancer 15 months earlier. A follow-up chest computed tomography after the chemotherapy showed that the right lower lobe bronchus was obstructed, and it was necessary to differentiate a primary lung malignancy from a metastasis and secretion. A positron emission tomography revealed an intense hypermetabolic nodule in the right lower lobe bronchus and diffuse hypometabolism of the right lower lobe lung. Bronchoscopy revealed a tumor mass obstructing the right lower lobe bronchus, and an endobronchial biopsy confirmed a metastatic serous carcinoma from the endometrium. We described an endobronchial metastasis from an endometrial carcinoma with various diagnostic images and histology. To the best of our knowledge, this is the first report of an endobronchial metastasis from an endometrial carcinoma in Korea.

To understand how human cytomegalovirus (HCMV) might change and evolve after reactivation, it is very important to understand how the nucleotide sequence of cultured HCMV changes after in vitro passaging in cell culture, and how these changes affect the genome of HCMV and the consequent variation in amino acid sequence. Strain JHC of HCMV was propagated in vitro for more than 40 passages and its biological and genetic changes were monitored. For each passage, real-time PCR was performed in order to determine the genome copy number, and a plaque assay was employed to get virus infection titers. The infectious virus titers gradually increased with passaging in cell culture, whereas the number of virus genome copies remained relatively unchanged. A linear correlation was observed between the passage number and the log10 infectious virus titer per virus genome copy number. To understand the genetic basis underlying the increase in HCMV infectivity with increasing passage, the whole-genome DNA sequence of the high-passage strain was determined and compared with the genome sequence of the low-passage strain. Out of 100 mutations found in the high-passage strain, only two were located in an open reading frame. A G-T substitution in the RL13 gene resulted in a nonsense mutation and caused an early stop. A G-A substitution in the UL122 gene generated an S-F nonsynonymous mutation. The mutations in the RL13 and UL122 genes might be related to the increase in virus infectivity, although the role of the mutations found in noncoding regions could not be excluded.

Coronary artery aneurysm is a rare congenital or vascular inflammation-based anomaly for which the clinical course and optimal timing of treatment remain unclear. Here, we report a case of sudden death caused by a giant coronary artery aneurysm of the left anterior descending artery that presented with chest pain. This case suggests that urgent interventional or surgical repair is needed when a large coronary aneurysm presents with acute ischemic symptoms.

Background/Aims: To compare the clinical outcomes of ‘on-label’ and ‘off-label’ drug-eluting stents (DESs) over a 5-year follow-up period. Methods: A total of 929 patients that underwent percutaneous coronary intervention with DESs were enrolled. Patients were divided into two groups according to on-label (n = 449) and off-label (n = 480) indications. Off-label use was defined as implantation of DESs for acute myocardial infarction (MI), very small vessel, a long stenotic lesion, chronic total occlusion, a bifurcation lesion, an ostial lesion, left main coronary artery disease, multivessel disease, a saphenous vein graft lesion, and a lesion with thrombus. Endpoints were composite of major adverse cardiac events (MACEs), which included all-cause death, ischemic-driven target vessel revascularization (Id-TVR), MI, and stent thrombosis (ST). Clinical outcomes in the two groups were compared for up to 5 years postimplantation. Results: At 1 year postimplantation, the off-label group had higher incidences of total MACEs (8.2% vs. 3.7%, p = 0.005), Id-TVR (5.0% vs. 1.6%, p = 0.004), and ST (1.7% vs. 0.3%, p = 0.042), and at 5 years postimplantation, the off-label group continued to have higher incidences of total MACEs (17.5% vs. 9.4%, p < 0.001), Id- TVR (13.1% vs. 5.8%, p = 0.024), and ST (2.1% vs. 0.3%, p = 0.021). Multivessel disease and diabetes were found to be independent risk factors of MACE in patients with an off-label indication. Conclusions: Patients treated with an on-label DES had better long-term clinical outcomes than those treated with an off-label DES.

Soluble suppression of tumorigenicity 2 (sST2) is known as a strong risk predictor in patients with heart failure (HF) and provides additional prognostic value to NT-proBNP. The purpose of this study is to investigate the value of sST2 in Atrial fibrillation (AF) patients. We enrolled 596 patients

Outstanding performance has been achieved in resolving recognition and classification problems with deep learning technology. As increasing amounts of gene expression data from cancer and normal samples become publicly available, deep learning may become an integral component of revealing specific patterns within massive data sets. Thus, we aimed to address the extent to which a deep learning can learn to recognise cancer. We integrated gene expression data from the Gene Expression Omnibus (GEO), The Cancer Gene Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases, including 13,406 cancer and 12,842 normal gene expression data from 24 different tissues. We first trained a Deep Neural Network (DNN) to identify cancer and normal samples using various gene selection strategies. Genes of high expression or large variance, therapeutic target genes from commercial cancer panels, and genes in NCI-curated cancer pathways. We also suggest a systematic analysis method to interpret trained deep neural networks. We applied the method to find genes that majorly contribute to classify cancer in an individual sample.

Background: Deep learning has proven to show outstanding performance in resolving recognition and classification problems. As increasing amounts of cancer and normal gene expression data become publicly available, deep learning may become an integral component of efficiently finding specific patterns within massive datasets. Thus, we aim to address the extent to which the machine can learn to recognize cancer. We integrated cancer and normal tissue data from the Gene Expression Omnibus (GEO), The Cancer Gene Atlas (TCGA), Therapeutically Applicable Research To Generate Effective Treatments (TARGET), and Genotype-Tissue Expression (GTEx) databases, including 13,406 cancer and 12,842 normal gene expression data from 24 different tissues. We first trained the deep neural network (DNN) to discriminate between cancer and normal samples using various gene selection strategies and therapeutic target genes from commercial cancer panels and genes in NCI-curated cancer pathways. We also suggest systemic analyzation method to interpret trained deep neural network. We applied the method to find genes mostly contribute to classify cancer in an individual sample. Result: The best trained DNN could classify cancer and normal data with accuracy of 0.997 in the training data set of 13,123 (cancer: 6,703, normal: 6,402) samples. In the independent test set comprising 13,125 (cancer: 6,703, normal: 6,422) samples, the DNN model achieved 0.979 accuracy. Using the same training and test data, our DNN showed better performance than other conventional prediction methods, followed by the support vector machine approach. For interpretation, we propose a method that can extract a gene’s contribution to an individual sample’s cancer probability from the trained DNN. This method distinguished samples dependent on one or a few genes suggesting these samples are possibly}}{{\it “oncogene addicted”. Conclusion: A deep learning approach in conjunction with our interpretation method is not only a useful tool to identify cancer from gene expression data but can also contribute toward understanding the complex nature of cancer based on large public data.

Hypothalamic regulation of appetite governs whole-body energy balance. Satiety is regulated by endocrine factors, including leptin, and impaired leptin induction causes obesity. Angiopoietin-like growth factor (AGF) promotes energy expenditure in the periphery, and systemic reconstitution of AGF antagonizes obesity. However, whether hypothalamic AGF plays a role in controlling food intake remains unknown. Here, we demonstrated that AGF is expressed in proopiomelanocortin (POMC)-positive neurons located in the arcuate nucleus (ARC) of the hypothalamus. AGF expression was stimulated by leptin-induced STAT3 phosphorylation. Notably, intracerebroventricular injection of AGF significantly reduced food intake by stimulating phosphorylation of CREB in the POMC and increasing α-melanocyte-stimulating hormone (α-MSH) content in the hypothalamus. We also found that hypothalamic injection of AGF significantly suppressed food intake and decreased body weight in high-fat-diet-induced obese mice, which exhibit leptin insensitivity. Collectively, our findings demonstrate that hypothalamic AGF provokes the anorectic melanocortin pathway and mediates leptin signaling to prevent obesity. Funding: This work was supported by the National Research Foundation of South of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (MSIP) (2017R1E1A1A01075126, 2014R1A6A1029617, 2016R1A2B4010398, 2016R1D1A1B03932766, 2017R1A5A201538, 2017R1A6A3A11029367) and research fund of Chungnam National University Declaration of Interest: The authors have declared that no conflict of interests existed. Ethical Approval: Animal experiments were approved by the Institutional Animal Care and Use Committee of Chungnam National University (ethical approval number, CNU-00912). The hypothalamus was obtained from postmortem brains of otherwise healthy individuals at the University of Miyazaki, Japan, with the approval of institutional review board (approval number, C-0037; May 11, 2018). Written informed consent was acquired from each outpatient, and the study was conducted according to provisions of the Declaration of Helsinki.

Varicella-zoster virus (VZV) is an important viral pathogen that is responsible for causing varicella (chickenpox) and herpes zoster (shingles). VZV has been shown to suppress early anti-viral innate immune responses, but the exact mechanisms are not yet well understood. Here we demonstrate that host control of VZV is impaired by the expression of suppressor of cytokine signaling (SOCS)3. We used three different cell types to characterize VZV-induced anti-viral and inflammatory responses. Infection of human fibroblasts (MRC-5) and human macrophages (THP-1) with VZV triggered upregulation of anti-viral responsive gene expression (IFN-α, IFN-β) in the early phases of infection, followed by the waning of these IFNs in the late phases of infection. Conversely, VZV infection in keratinocytes (HaCaT) resulted in a persistent increase in type I IFN gene expression. Interestingly, increase in SOCS1 and 3 expressions coincided with a reduction in phosphorylation of the signal transducer and activator of transcription protein 3 (STAT3) in VZV-infected MRC-5 cells. Furthermore, VZV infection increased the production of pro-inflammatory cytokines, including interleukin (IL)-6, -8, and IFN-γ-inducible protein 10 (IP-10). Knockdown of SOCS3 inhibited viral replication and enhanced secretion levels of IL-6, whereas overexpression of SOCS3 did not affect viral replication efficiency and host response. In conclusion, our data suggest that VZV infection induces SOCS3 expression, resulting in modulation of type I IFN signaling and viral replication.

Myocardial bridging (MB) is mostly confined to the left anterior descending coronary artery (LAD) and has been reported to be correlated with increased atherosclerotic plaques in the segment proximal to the bridging. This study aimed to assess the impact of MB on the clinical outcomes of patients with DES implantation in the LAD.A total of 551 consecutive patients with DES implantation on LAD from January 2008 to December 2009 were included. Patients were divided into an MB group (n=94, 17.1%) and a non-MB group (n=457, 82.9%) based on angiographic findings. They were followed up for three years to evaluate major adverse cardiac events (MACE), which were defined as all-cause death, myocardial infarction (MI), target lesion revascularisation (TLR) or ischaemic driven target vessel revascularisation (Id-TVR).During three years of follow-up, the rate of MACE was significantly higher in the MB group than in the non-MB group (18.1% vs. 9.8%, p=0.024), especially rates of TLR (8.5% vs. 2.4%; p=0.003) and Id-TVR (13.8% vs. 4.2%; p0.001). However, no difference was observed for MI (3.2 vs. 2.6%; p=0.692) and all-cause death rates (3.2 vs. 4.6%; p=0.575). Multivariate regression analysis showed that the presence of MB was an independent predictor for MACE (Hazard ratio 2.897, 95% CI 1.536 - 5.464, p=0.001).MB appears to be associated with adverse effects in patients with DES implantation in the LAD.

The classical biotype strains of the Vibrio cholerae O1 serogroup harbor the biotype-specific cholera-toxin encoding phage (CTX) CTX(cla), and the El Tor biotype strains contain CTX-1. Although the classical biotype strains have become extinct, a remnant of classical CTX phage is transferred to the El Tor biotype strains. The prototype El Tor strains, which produce the biotype-specific cholera toxin, are now being replaced by atypical El Tor variant strains producing classical biotype cholera toxin. The genome sequences of the CTX phages in atypical El Tor strains indicate that the CTX phages in atypical El Tor strains are a mosaic of CTXcla and CTX-1. Before the emergence of atypical El Tor stains in the early 1990s, unusual pre-seventh pandemic strains were isolated in the US Gulf Coast between 1973 and 1986. These strains have characteristics of atypical El Tor strains since they are El Tor biotype strains containing CTX(cla), yet the genome sequence of this CTX phage indicates that it is different from CTXcla and is therefore classified separately as CTX(US Gulf).

The aim of this study was to compare the intensity-based statin therapy and attained low-density lipoprotein cholesterol (LDL-C) based therapy in patients with AMI, using the nationwide, multicenter, prospective KAMIR-NIH (Korean Acute Myocardial Infarction-National Institutes of Health) registry.

Patient Initials or Identifier Number LDS ### Relevant Clinical History and Physical Exam A 74 year-old man visited our hospital for dyspnea (NYHA III). He had a medical history of hypertension, diabetes mellitus, and stable angina. Physical examination showed regular heart beat with systolic

Recent guideline emphasized strict blood pressure (BP) control for the patients at high risk for cardiovascular events. We sought to compare clinical outcome between intensive versus usual BP control in patients with coronary artery disease (CAD) received drug-eluting stent (DES). We reviewed 1,009

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi, and the clinical course varies from mild and self-limiting to fatal. We describe a rare case of a pulmonary artery thrombosis associated with scrub typhus. Vasculitis via endothelial dysfunction caused by scrub typhus could be considered as the main mechanism.

Ganciclovir resistance of human cytomegalovirus is associated with mutations in the viral UL97 gene and poses severe problems for immunocompromised patients. In this study, PCRbased restriction fragment length polymorphism and sequencing analyses detected the UL97 D605E mutation in all five clinical isolates from patients with ganciclovir-resistant human cytomegalovirus infection during prolonged ganciclovir therapy, whereas the M460V mutation was only present in 1 of 5 isolates. On the other hand, the detection rates of the D605E mutation in the stored available DNA samples from the donor and allogeneic stem cell transplantation recipients were 66.7% and 93.7%, respectively, suggesting that the presence of D605E mutation was not associated with the ganciclovir exposure. Although the D605E mutation may not be related to ganciclovir resistance, we suggest that this mutation could be an important molecular marker of human cytomegalovirus evolution in East Asian countries. Moreover, the restriction fragment length polymorphism method using the restriction enzyme HaeIII, which is generally used to detect the UL97 A591V mutation, could also detect the D605E mutation and may therefore be a useful tool for future research on the investigation of UL97 gene mutations.

In this technique development study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to non-invasively image and quantify 3D joint space morphology of the wrist and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA). HR-pQCT imaging (82 μm voxel-size) of the dominant hand was performed in patients with diagnosed rheumatoid arthritis (RA, N = 16, age: 52.6 ± 12.8) and healthy controls (CTRL, N = 7, age: 50.1 ± 15.0). An automated computer algorithm was developed to segment wrist and MCP joint spaces. The 3D distance transformation method was applied to spatially map joint space width, and summarized by the mean joint space width (JSW), minimal and maximal JSW (JSW.MIN, JSW.MAX), asymmetry (JSW.AS), and distribution (JSW.SD)—a measure of joint space heterogeneity. In vivo precision was determined for each measure by calculating the smallest detectable difference (SDD) and root mean square coefficient of variation (RMSCV%) of repeat scans. Qualitatively, HR-pQCT images and pseudo-color JSW maps showed global joint space narrowing, as well as regional and focal abnormalities in RA patients. In patients with radiographic JSN at an MCP, JSW.SD was two-fold greater vs. CTRL (p

The aim of this study was to identify the factors associated with gout among South Koreans. A case control study of gout patients newly diagnosed between January 1, 2007, and December 31, 2008, and matching controls was conducted using the nationwide database (National Health Insurance Corporation and National Health Screening Exam (NHSE) database), which included the health-care records of 48.1 million individuals. Of 495,998 newly diagnosed patients, we included 18,123 who were ≥40 years old and had an NHSE before diagnosis of gout. To elucidate the factors associated with gout, multivariate conditional logistic analyses were performed. Gout was associated with drinking ≥1/week (p

SUMMARY Obesity-associated metabolic alterations are closely linked to low-grade inflammation in peripheral organs, in which macrophages play a central role. Using genetic labeling of myeloid lineage cells, we show that hypothalamic macrophages normally reside in the perivascular area and circumventricular organ median eminence. Chronic consumption of a high-fat diet (HFD) induces expansion of the monocyte-derived macrophage pool in the hypothalamic arcuate nucleus (ARC), which is significantly attributed to enhanced proliferation of macrophages. Notably, inducible nitric oxide synthase (iNOS) is robustly activated in ARC macrophages of HFD-fed obese mice. Hypothalamic macrophage iNOS inhibition completely abrogates macrophage accumulation and activation, proinflammatory cytokine overproduction, reactive astrogliosis, blood-brain-barrier permeability, and lipid accumulation in the ARC of obese mice. Moreover, central iNOS inhibition improves obesity-induced alterations in systemic glucose metabolism without affecting adiposity. Our findings suggest a critical role for hypothalamic macrophage-expressed iNOS in hypothalamic inflammation and abnormal glucose metabolism in cases of overnutrition-induced obesity., In Brief Lee et al. demonstrate in mice that, upon prolonged high-fat diet feeding, hypothalamic macrophages proliferate, expand their pool, and sustain hypothalamic inflammation. Moreover, they show that hypothalamic macrophage iNOS inhibition diminishes macrophage activation, astrogliosis, blood-brain-barrier permeability, and impaired glucose metabolism in diet-induced obese mice., Graphical Abstract

BACKGROUND AND OBJECTIVES This study was performed to describe clinical characteristics of patients with left ventriculars (LV) dysfunction and implantable cardioverter-defibrillator (ICD), and to evaluate the effect of ICD therapy on survival in Yeongnam province of Korea. SUBJECTS AND METHODS From a community-based device registry (9 centers, Yeongnam province, from November 1999 to September 2012), 146 patients with LV dysfunction and an ICD implanted for primary or secondary prophylaxis, were analyzed. The patients were divided into two groups, based on the etiology (73 with ischemic cardiomyopathy and 73 with non-ischemic cardiomyopathy), and indication for the device implantation (36 for primary prevention and 110 for secondary prevention). The cumulative first shock rate, all cause death, and type and mode of death, were determined according to the etiology and indication. RESULTS Over a mean follow-up of 3.5 years, the overall ICD shock rate was about 39.0%. ICD shock therapy was significantly more frequent in the secondary prevention group (46.4% vs. 16.7%, p=0.002). The cumulative probability of a first appropriate shock was higher in the secondary prevention group (p=0.015). There was no significant difference in the all-cause death, cardiac death, and mode of death between the groups according to the etiology and indication. CONCLUSION Studies from this multicenter regional registry data shows that in both ischemic and non-ischemic cardiomyopathy patients, the ICD shock therapy rate was higher in the secondary prevention group than primary prevention group.

The objective of this study is to investigate the value of multidetector computed tomography (MDCT) in the assessment of sacroiliitis in patients with established ankylosing spondylitis (AS). Paired plain radiographs and MDCT images of the 330 sacroiliac (SI) joints in 165 patients with definite or probable ankylosing spondylitis were analyzed for sacroiliitis. Sacroiliitis on plain radiographs were graded on a scale of 0-4 according to the modified New York (NY) criteria. For grading of sacroiliitis by MDCT, modified NY criteria were revised for MDCT application introducing the concept of quantification. The relationship between sacroiliitis grades by plain radiography and MDCT was analyzed by two radiologists, blinded for all clinical data. Of the 330 SI joints assessed, there was agreement between the sacroiliitis grading by plain radiography and MDCT in 73 (22.1 %) SI joints. Sacroiliitis grade by MDCT was higher in 250 (75.8 %) SI joints and lower in 7 (2.1 %) SI joints than that by plain radiography. Using the MDCT, 83.6 % of patients met the modified NY radiologic criteria for the classification of AS, compared with 58.2 % of the patients by plain radiography. Twenty-six percent of the patients, who did not meet the modified NY criteria for the classification of AS by plain radiography, met the criteria by MDCT. Disease durations in patients with grade 2 and grade 3 sacroiliitis were significantly shorter in patients evaluated by MDCT compared with plain radiography. MDCT is a useful imaging method that can be applied to the initial diagnosis of the AS, and by better visualization of SI joint changes, it can be used to predict the progress of the disease.

The interferon-inducible Sp100 proteins are thought to play roles in the chromatin pathway and in transcriptional regulation. Sp100A, the smallest isoform, is one of the major components of PML nuclear bodies (NBs) that exhibit intrinsic antiviral activity against several viruses. Since PML NBs are disrupted by the immediate-early 1 (IE1) protein during human cytomegalovirus (HCMV) infection, the modulation of Sp100 protein expression or activity during infection has been suggested. Here, we show that Sp100 proteins are lost largely in the late stages of HCMV infection. This event required viral gene expression and involved posttranscriptional control. The mutant virus with deletion of the sequence for IE1 (CR208) did not have Sp100 loss. In CR208 infection, PML depletion by RNA interference abrogated the accumulation of SUMO-modified Sp100A and of certain high-molecular-weight Sp100 isoforms but did not significantly affect unmodified Sp100A, suggesting that the IE1-induced disruption of PML NBs is not sufficient for the complete loss of Sp100 proteins. Sp100A loss was found to require proteasome activity. Depletion of all Sp100 proteins by RNA silencing enhanced HCMV replication and major IE (MIE) gene expression. Sp100 knockdown enhanced the acetylation level of histones associated with the MIE promoter, demonstrating that the repressive effect of Sp100 proteins may involve, at least in part, the epigenetic control of the MIE promoter. Sp100A was found to interact directly with IE1 through the N-terminal dimerization domain. These findings indicate that the IE1-dependent loss of Sp100 proteins during HCMV infection may represent an important requirement for efficient viral growth.

Background: Recent recommendations have established clinical remission ideally or low disease activity (LDA) as therapeutic targets in all patients with rheumatoid arthritis (RA). Controlled studies of biologic agents have primarily assessed treatment effects in patients with severe RA; patients with moderate disease activity, whoconstitute a larger group, have received far less attention. In Period 1 of the PRESERVE trial, the proportion of subjects with moderately active RA achieving LDA or remission were evaluated after treatment with etanercept 50mg once weekly (QW) plus methotrexate for 36 weeks.Methods: Subjects with DAS28 >3.2 and ≤5.1 despite stable doses of oral methotrexate received open-label etanercept 50mg QW plus methotrexate (screening dose permitted to be titrated up to 25 mg/wk through week 28) for 36 weeks.Results: 834 subjects received treatment and were analyzed. Subjects were mostly female (83%), Caucasian (74%), RFþ (73%), and aCCPþ (78%), with a mean age of 48 years and disease duration of 7 years. Mean baseline DAS28 was 4.4; SDAI, 19.1; ESR, 22.2 mm/hr; and CRP, 12.3 mg/L. Efficacy results from Period 1 are shown in the table. The most commonly reported adverse events (AEs) were headache (6.1%), nasopharyngitis (5.4%), and upper respiratory tract infection (4.4%). Twenty-two subjects (2.6%) discontinued due to AEs.Conclusions: Substantial proportions of subjects with moderately active RA who received etanercept 50mg QW plus methotrexate for 36 weeks achieved LDA (85%-86%), DAS28 remission (67%), or SDAI remission (25%). Therefore, these ambitious goals can be achieved realistically in a high percentage of patients with moderate disease activity.

Although current guidelines have recommended high-intensity statin therapy for patients with acute myocardial infarction (AMI), the effectiveness of high-intensity statin is uncertain in Korean AMI populations. Between November 2011 and January 2016, a total of 11839 AMI patients in the Korean

BACKGROUND Hemorheologic indices are known to be related to vascular complications in variable clinical settings. However, little is known about the associations between hemorheologic parameters and acute myocardial infarction (AMI) in type 2 diabetes mellitus (T2DM). The purpose of this study was to demonstrate the changes of hemorheologic environment inside of blood using hemorheologic parameters, especially the elongation index (EI) and critical shear stress (CSS) in diabetics with versus without AMI. METHODS A total of 195 patients with T2DM were enrolled. Patients were divided into the study group with AMI (AMI+, n=77) and control group (AMI-, n=118) who had no history of coronary artery disease. Hemorheologic parameters such as EI and CSS were measured and compared between the two groups. RESULTS The EI was lower (30.44%±1.77% in AMI+ and 31.47%±1.48% in AMI-, P

Background Magnesium is well known to inhibit catecholamine release and attenuate vasopressin-stimulated vasoconstriction. We investigated whether i.v. magnesium sulphate attenuates the haemodynamic stress responses to pneumoperitoneum by changing neurohumoral responses during laparoscopic cholecystectomy. Methods Thirty-two patients undergoing laparoscopic cholecystectomy were randomly assigned to two groups; a control group was given saline, and a magnesium group received magnesium sulphate 50 mg kg−1 immediately before pneumoperitoneum. Arterial pressure, heart rate, serum magnesium, plasma renin activity (PRA), and catecholamine, cortisol, and vasopressin levels were measured. Results Systolic and diastolic arterial pressures were greater in the control group (P Conclusions I.V. magnesium sulphate before pneumoperitoneum attenuates arterial pressure increases during laparoscopic cholecystectomy. This attenuation is apparently related to reductions in the release of catecholamine, vasopressin, or both.

Hwaeumjeon is a classical prescription that has been traditionally used for treatment of urogenital diseases with no scientific evidences until now. Thus, the present study was performed to evaluate antitumor mechanism of ethanolic Hwaeumjeon (EHEJ). 2-Dimensional electrophoresis (2-DE) proteomic analysis, cell culture study, and Western blotting on apoptosis and prostate-specific antigen (PSA) related proteins were carried out in LNCaP prostate cancer cells. Eight spots with significant increased or decreased expression revealed by 2-DE based comparative proteomic analysis were identified as an increased protein ENC-1AS, four decreased proteins such as RAB34, SFRS1, heat shock 27, and proteasome activator, and three novel proteins such as Rho GDP dissociation inhibitor alpha, cytoplasmic antiproteinase, and EIF3EIP protein in EHEJ-treated LNCaP cells. In addition, EHEJ selectively inhibited the growth of LNCaP prostate cancer cells compared to normal human umbilical vein endothelial cells. Furthermore, EHEJ inhibited PSA and androgen receptor (AR) expression in androgen sensitive LNCaP prostate cancer cells at nontoxic concentrations. Also, EHEJ increased sub-G1 apoptotic portion, activated caspase-9 and -3, cleaved poly (ADP-ribose) polymerase (PARP) and increased the ratio of Bax to Bcl-2. Interestingly, EHEJ also attenuated phosphatidylinositol-3 kinase (PI3K) expression and suppressed the phosphorylation of survival gene AKT, ERK, and HSP27 in LNCaP cells. Consistently, PI3K and ERK inhibitors potentiated EHEJ-induced cytotoxicity and overexpression of Bcl-2 attenuated EHEJ-mediated apoptosis in LNCaP cells. These findings suggest that EHEJ induces mitochondrial dependent apoptosis partly via PI3K/AKT/HSP27/ERK pathways and inhibits PSA and AR in LNCaP cells as a prostate cancer chemopreventive candidate.

Cancer pain impairs the quality of life of cancer patients, but opioid analgesics can not only cause inhibition of respiratory function, and constipation, but also other significant side effects such as addiction and tolerance that further decrease quality of life. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in cancer pain mouse model. In order to induce neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. The mass of S-180 cancer cells embedded around sciatic nerve in a time course was confirmed by Magnetic Resonance Imaging (MRI) scanning. Mechanical allodynia was most consistently induced in mouse sarcoma cell line S-180 (2 x 10(6) sarcoma cells) treated group among all groups. EA stimulation (2Hz) was daily given to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation. EA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation as well as shortened cumulative lifting duration from 7 days after inoculation compared with tumor control. In addition, the overexpressions of pain peptide substance P in dorsal horn of spinal cord were significantly decreased in EA treated group compared with tumor control on Day 9 after inoculation. Furthermore, EA treatment effectively increased the concentration of beta endorphin in blood and brain of mice more than tumor control as well as normal group. The concentration of beta-endorphin for EA treatment group increased by 51.457% in blood 12.6% in brain respectively, compared with tumor control group. These findings suggest that S-180 cancer pain model can be a consistent and short time animal model and also EA treatment can be an alternative therapeutic method for cancer pain via decreased substance P and increased beta endorphin.