Publications by authors named "Eun-Kyoung Kim"

221 Publications

Comparative metabolic profiling of posterior parietal cortex, amygdala, and hippocampus in conditioned fear memory.

Mol Brain 2021 Oct 6;14(1):153. Epub 2021 Oct 6.

Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.

Fear conditioning and retrieval are suitable models to investigate the biological basis of various mental disorders. Hippocampus and amygdala neurons consolidate conditioned stimulus (CS)-dependent fear memory. Posterior parietal cortex is considered important for the CS-dependent conditioning and retrieval of fear memory. Metabolomic screening among functionally related brain areas provides molecular signatures and biomarkers to improve the treatment of psychopathologies. Herein, we analyzed and compared changes of metabolites in the hippocampus, amygdala, and posterior parietal cortex under the fear retrieval condition. Metabolite profiles of posterior parietal cortex and amygdala were similarly changed after fear memory retrieval. While the retrieval of fear memory perturbed various metabolic pathways, most metabolic pathways that overlapped among the three brain regions had high ranks in the enrichment analysis of posterior parietal cortex. In posterior parietal cortex, the most perturbed pathways were pantothenate and CoA biosynthesis, purine metabolism, glutathione metabolism, and NAD dependent signaling. Metabolites of posterior parietal cortex including 4'-phosphopantetheine, xanthine, glutathione, ADP-ribose, ADP-ribose 2'-phosphate, and cyclic ADP-ribose were significantly regulated in these metabolic pathways. These results point to the importance of metabolites of posterior parietal cortex in conditioned fear memory retrieval and may provide potential biomarker candidates for traumatic memory-related mental disorders.
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http://dx.doi.org/10.1186/s13041-021-00863-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493686PMC
October 2021

Investigation of progression pattern and associated risk factors in glaucoma patients with initial paracentral scotomas using Humphrey 10-2.

Sci Rep 2021 09 20;11(1):18609. Epub 2021 Sep 20.

Department of Ophthalmology, Seoul St. Mary's Hospital, 505 Banpo-dong, Seocho-ku, Seoul, 137-701, Korea.

Central visual field (VF) progression could directly threaten patientss visual function compared to glaucomatous damage. This study was designed to investigate visual field (VF) progression pattern and associated risk factors including optical coherence topography angiographic (OCT-A) findings in glaucoma patients with initial paracentral scotoma. This prospective, observational study included 122 eyes presenting as initial paracentral scotomas with serial 24-2 and 10-2 VF tests at the glaucoma clinic of Seoul St Mary's Hospital between November 2017 and August 2020. The participants underwent at least 5 serial VF exams and OCT-A at baseline. Numerical values of the initial and final 10-2 VF tests were averaged for each VF test point using the total deviation map. Innermost 10-2 VF progression was defined as three or more new contiguous points at the central 12 points on 10-2 VF. Other clinical characteristics were collected including history of disc hemorrhage and vessel density (VD) was measured from OCT-A images. Linear regression analysis was performed to obtain the change of mean deviation and a cut-off for progression was defined for both 24-2 and 10-2 VFs. The average total deviation maps of the initial 10-2 VF tests shows initial paracentral scotoma located in the superior region in an arcuate pattern that was deep in the 4°-6° region above fixation. This arcuate pattern was more broadly located in the 4°-10° region in the primary open-angle glaucoma (POAG) group, while it was closer to fixation in 0°-4° region in the normal-tension glaucoma (NTG) group. The final average map shows deepening of scotomas in the 4°-10° region in POAG, which deepened closer to the region of fixation in NTG. The diagnosis of NTG (β 1.892; 95% CI 1.225-2.516; P = 0.035) and lower choroidal VD in the peripapillary atrophy (PPA) region (β 0.985; 95% CI 0.975 to 0.995; P = 0.022) were significantly related to innermost 10-2 VF progression. Initial paracentral scotomas in NTG tended to progress closer to the region of fixation, which should be monitored closely. Important progression risk factors related to paracentral scotoma near the fixation were the diagnosis of NTG and reduced choroidal VD in the β-zone PPA region using OCT-A. We should consider vascular risk factors in NTG patients presenting with initial paracentral scotoma to avoid vision threatening progression of glaucoma.
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http://dx.doi.org/10.1038/s41598-021-97446-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452676PMC
September 2021

Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects.

Sci Rep 2021 08 17;11(1):16697. Epub 2021 Aug 17.

Department of Ophthalmology, The Catholic University of Korea, Seoul, Korea.

This study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 μm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5-6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.
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http://dx.doi.org/10.1038/s41598-021-95984-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371169PMC
August 2021

Liver-Specific Deletion of Mouse CTCF Leads to Hepatic Steatosis via Augmented PPARγ Signaling.

Cell Mol Gastroenterol Hepatol 2021 Aug 4;12(5):1761-1787. Epub 2021 Aug 4.

Department of Environmental Medical Biology, Institute of Tropical Medicine, Seoul, Korea; Brain Korea 21 Plus Project for Medical Science, Seoul, Korea. Electronic address:

Background & Aims: The liver is the major organ for metabolizing lipids, and malfunction of the liver leads to various diseases. Nonalcoholic fatty liver disease is rapidly becoming a major health concern worldwide and is characterized by abnormal retention of excess lipids in the liver. CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein that regulates higher-order chromatin organization and is involved in various gene regulation processes. Here, we sought to determine the physiological role of CTCF in hepatic lipid metabolism.

Methods: We generated liver-specific, CTCF-ablated and/or CD36 whole-body knockout mice. Overexpression or knockdown of peroxisome proliferator-activated receptor (PPAR)γ in the liver was achieved using adenovirus. Mice were examined for development of hepatic steatosis and inflammation. RNA sequencing was performed to identify genes affected by CTCF depletion. Genome-wide occupancy of H3K27 acetylation, PPARγ, and CTCF were analyzed by chromatin immunoprecipitation sequencing. Genome-wide chromatin interactions were analyzed by in situ Hi-C.

Results: Liver-specific, CTCF-deficient mice developed hepatic steatosis and inflammation when fed a standard chow diet. Global analysis of the transcriptome and enhancer landscape revealed that CTCF-depleted liver showed enhanced accumulation of PPARγ in the nucleus, which leads to increased expression of its downstream target genes, including fat storage-related gene CD36, which is involved in the lipid metabolic process. Hepatic steatosis developed in liver-specific, CTCF-deficient mice was ameliorated by repression of PPARγ via pharmacologic blockade or adenovirus-mediated knockdown, but hardly rescued by additional knockout of CD36.

Conclusions: Our data indicate that liver-specific deletion of CTCF leads to hepatosteatosis through augmented PPARγ DNA-binding activity, which up-regulates its downstream target genes associated with the lipid metabolic process.
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http://dx.doi.org/10.1016/j.jcmgh.2021.07.016DOI Listing
August 2021

Autophagic defects observed in fibroblasts from a patient with β-propeller protein-associated neurodegeneration.

Am J Med Genet A 2021 Jul 29. Epub 2021 Jul 29.

Neural Circuit Research Group, Korea Brain Research Institute, Daegu, South Korea.

Beta-propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate autophagic defects in a patient with BPAN. We assayed autophagic markers using western blot analysis and immunocytochemistry and applied transmission electron microscopy (TEM) to visualize the autophagic structures in fibroblasts from a 7-year-old Korean female with WDR45 splice-site mutation (c.977-1G>A; NM_007075.3). The protein and mRNA expression levels of WDR45 gene were decreased in the patient-derived fibroblasts. The amount of increase in LC3-II upon treatment with an autophagy inducer and inhibitor was reduced in mutant cells compared to control cells, suggesting decreased autophagic flux. TEM showed the accumulation of large vacuoles in mutant cells with a decrease of autophagosomes. Our study demonstrated that the WDR45 mutation in this patient impaired autophagy and provided additional insight into ultrastructural changes of autophagic structures.
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http://dx.doi.org/10.1002/ajmg.a.62442DOI Listing
July 2021

Biglycan reduces body weight by regulating food intake in mice and improves glucose metabolism through AMPK/AKT dual pathways in skeletal muscle.

FASEB J 2021 08;35(8):e21794

Interdisciplinary Program in Precision Public Health, Korea University, Seoul, Republic of Korea.

While biglycan (BGN) is suggested to direct diverse signaling cascades, the effects of soluble BGN as a ligand on metabolic traits have not been studied. Herein, we tested the effects of BGN on obesity in high-fat diet (HFD)-induced obese animals and glucose metabolism, with the underlying mechanism responsible for observed effects in vitro. Our results showed that BGN administration (1 mg/kg body weight, intraperitoneally) significantly prevented HFD-induced obesity, and this was mainly attributed to reduced food intake. Also, intracerebroventricular injection of BGN reduced food intake and body weight. The underlying mechanism includes modulation of neuropeptides gene expression involved in appetite in the hypothalamus in vitro and in vivo. In addition, BGN regulates glucose metabolism as shown by improved glucose tolerance in mice as well as AMPK/AKT dual pathway-driven enhanced glucose uptake and GLUT4 translocation in L6 myoblast cells. In conclusion, our results suggest BGN as a potential therapeutic target to treat risk factors for metabolic diseases.
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http://dx.doi.org/10.1096/fj.202002039RRDOI Listing
August 2021

Functional recovery of a novel knockin mouse model of dysferlinopathy by readthrough of nonsense mutation.

Mol Ther Methods Clin Dev 2021 Jun 1;21:702-709. Epub 2021 May 1.

Neurology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnamdo 50612, Republic of Korea.

Biallelic mutations in the dysferlin gene cause limb-girdle muscular dystrophy 2B or Miyoshi distal myopathy. We found that nonsense mutations are the most common mutation type among Korean patients with dysferlinopathy; more than half of the patients have at least one nonsense allele, which may be amenable to readthrough therapy. We generated a knockin mouse, , harboring p.Q832∗ mutation. Homozygous mice lacked dysferlin in skeletal muscle, while 2 weeks of oral ataluren restored dysferlin expression and ameliorated skeletal muscle pathology. Their physical performance improved, and protection against eccentric contractions was noted. The improvement was most evident in mice treated with oral ataluren of 0.9 mg/mL. These improvements were sustained for 8 weeks in ataluren-treated mice, while the parameters of A/J mice treated with ataluren over the same period did not improve. These results support that readthrough therapy by oral ataluren may also be applicable to dysferlinopathy patients with nonsense mutation.
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http://dx.doi.org/10.1016/j.omtm.2021.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181533PMC
June 2021

Heart defects and embryonic lethality in Asb2 knock out mice correlate with placental defects.

Cells Dev 2021 03 27;165:203663. Epub 2021 Jan 27.

College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea. Electronic address:

Asb2, ankyrin repeat, and SOCS box protein 2 form an E3 ubiquitin ligase complex. Asb2 ubiquitin ligase activity drives the degradation of filamins, which have essential functions in humans. The placenta is a temporary organ that forms during pregnancy, and normal placentation is important for survival and growth of the fetus. Recent studies have shown that approximately 25-30% of knockout (KO) mice have non-viable offspring, and 68% of knockout lines exhibit placental dysmorphologies. There are very few studies on Asb2, with insufficient research on its role in placental development. Therefore, we generated Asb2 knockout mice and undertook to investigate Asb2 expression during organogenesis, and to identify its role in early embryonic and placental development. The external morphology of KO embryos revealed abnormal phenotypes including growth retardation, pericardial effusion, pale color, and especially heart beat defect from E 9.5. Furthermore, Asb2 expression was observed in the heart from E 9.5, indicating that it is specifically expressed during early heart formation, resulting in embryonic lethality. Histological analysis of E 10.5 KO heart showed malformations such as failure of chamber formation, reduction in trabeculated myocardium length, absence of mesenchymal cells, and destruction of myocardium wall. Moreover, the histological results of Asb2-deficient placenta showed abnormal phenotypes including small labyrinth and reduced vascular complexity, indicating that failure to establish mature circulatory pattern affects the embryonic development and results in early mortality. Collectively, our results demonstrate that Asb2 knockout mice have placental defects, that subsequently result in failure to form a normal cardiac septum, and thereby result in embryo mortality in utero at around E 9.5.
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http://dx.doi.org/10.1016/j.cdev.2021.203663DOI Listing
March 2021

Response of the microbiome-gut-brain axis in Drosophila to amino acid deficit.

Nature 2021 May 5;593(7860):570-574. Epub 2021 May 5.

National Creative Research Initiative Center for Hologenomics and School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.

A balanced intake of macronutrients-protein, carbohydrate and fat-is essential for the well-being of organisms. An adequate calorific intake but with insufficient protein consumption can lead to several ailments, including kwashiorkor. Taste receptors (T1R1-T1R3) can detect amino acids in the environment, and cellular sensors (Gcn2 and Tor) monitor the levels of amino acids in the cell. When deprived of dietary protein, animals select a food source that contains a greater proportion of protein or essential amino acids (EAAs). This suggests that food selection is geared towards achieving the target amount of a particular macronutrient with assistance of the EAA-specific hunger-driven response, which is poorly understood. Here we show in Drosophila that a microbiome-gut-brain axis detects a deficit of EAAs and stimulates a compensatory appetite for EAAs. We found that the neuropeptide CNMamide (CNMa) was highly induced in enterocytes of the anterior midgut during protein deprivation. Silencing of the CNMa-CNMa receptor axis blocked the EAA-specific hunger-driven response in deprived flies. Furthermore, gnotobiotic flies bearing an EAA-producing symbiotic microbiome exhibited a reduced appetite for EAAs. By contrast, gnotobiotic flies with a mutant microbiome that did not produce leucine or other EAAs showed higher expression of CNMa and a greater compensatory appetite for EAAs. We propose that gut enterocytes sense the levels of diet- and microbiome-derived EAAs and communicate the EAA-deprived condition to the brain through CNMa.
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http://dx.doi.org/10.1038/s41586-021-03522-2DOI Listing
May 2021

Multiscale characterization of ovariectomized rat femur.

J Biomech 2021 06 18;122:110462. Epub 2021 Apr 18.

Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Estrogen deficiency activates bone resorbing cells (osteoclasts) and to a lesser extent bone forming cells (osteoblasts), resulting in a gap between resorption and formation that leads to a net loss of bone. These cell activities alter bone architecture and tissue composition. Thus, the objective of this study is to examine whether multiscale (10 to 10 m) characterization can provide more integrated information to understand the effects of estrogen deficiency on the fracture risk of bone. This is the first study to examine the effects of estrogen deficiency on multiscale characteristics of the same bone specimen. Sprague-Dawley female rats (6 months old) were obtained for a bilateral ovariectomy (OVX) or a sham operation (sham). Micro-computed tomography of rat femurs provided bone volumetric, mineral density, and morphological parameters. Dynamic mechanical analysis, static elastic and fracture mechanical testing, and nanoindentation were also performed using the same femur. As expected, the current findings indicate that OVX reduces bone quantity (mass and bone mineral density) and quality (morphology, and fracture displacement). Additionally, they demonstrated reductions in amount and heterogeneity of tissue mineral density (TMD) and viscoelastic properties. The current results validate that multiscale characterization for the same bone specimen can provide more comprehensive insights to understand how the bone components contributed to mechanical behavior at different scales.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166321PMC
June 2021

Palmitate reduces starvation-induced ER stress by inhibiting ER-phagy in hypothalamic cells.

Mol Brain 2021 04 6;14(1):65. Epub 2021 Apr 6.

Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.

Palmitate is a saturated fatty acid that is well known to induce endoplasmic reticulum (ER) stress and autophagy. A high-fat diet increases the palmitate level in the hypothalamus, the main region of the brain regulating energy metabolism. Interestingly, hypothalamic palmitate level is also increased under starvation, urging the study to distinguish the effects of elevated hypothalamic palmitate level under different nutrient conditions. Herein, we show that ER-phagy (ER-targeted selective autophagy) is required for progress of ER stress and that palmitate decreases ER stress by inhibiting ER-phagy in hypothalamic cells under starvation. Palmitate inhibited starvation-induced ER-phagy by increasing the level of B-cell lymphoma 2 (Bcl-2) protein, which inhibits autophagy initiation. These findings suggest that, unlike the induction of ER stress under nutrient-rich conditions, palmitate protects hypothalamic cells from starvation-induced stress by inhibiting ER-phagy.
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http://dx.doi.org/10.1186/s13041-021-00777-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025501PMC
April 2021

GSK3B induces autophagy by phosphorylating ULK1.

Exp Mol Med 2021 Mar 2;53(3):369-383. Epub 2021 Mar 2.

Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.

Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian homolog of the yeast kinase Atg1, has an essential role in autophagy induction. In nutrient and growth factor signaling, ULK1 activity is regulated by various posttranslational modifications, including phosphorylation, acetylation, and ubiquitination. We previously identified glycogen synthase kinase 3 beta (GSK3B) as an upstream regulator of insulin withdrawal-induced autophagy in adult hippocampal neural stem cells. Here, we report that following insulin withdrawal, GSK3B directly interacted with and activated ULK1 via phosphorylation of S405 and S415 within the GABARAP-interacting region. Phosphorylation of these residues facilitated the interaction of ULK1 with MAP1LC3B and GABARAPL1, while phosphorylation-defective mutants of ULK1 failed to do so and could not induce autophagy flux. Furthermore, high phosphorylation levels of ULK1 at S405 and S415 were observed in human pancreatic cancer cell lines, all of which are known to exhibit high levels of autophagy. Our results reveal the importance of GSK3B-mediated phosphorylation for ULK1 regulation and autophagy induction and potentially for tumorigenesis.
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http://dx.doi.org/10.1038/s12276-021-00570-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080724PMC
March 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Impact of Atrial Fibrillation on Survival in Adults with Congenital Heart Disease: a Retrospective Population-based Study.

J Korean Med Sci 2021 Feb 1;36(5):e43. Epub 2021 Feb 1.

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The number of adults with congenital heart disease (ACHD) with atrial fibrillation (AF) is expected to increase. We sought to assess the impact of AF on survival in Korean ACHD.

Methods: Records of AF in ACHD were extracted from the records of the Korea National Health Insurance Service from 2006 through 2015. Multiple Cox proportional hazards analyses were carried out after adjustment for age, sex, income level, AF, and comorbidities. Survival rates (SRs) with and without AF were compared. The death records from 2006 through 2016 were included.

Results: A total of 3,999 ACHD had AF (51.4% were male) and 62,691 ACHD did not have AF (43.5% were male); the proportion of ACHD who were 60 years and older was 53.0% and 27.0% in those with and without AF, respectively ( < 0.001). The age-standardized incidence rate for AF was 1,842.0 persons per 100,000 people in the Korean general population from 2006 through 2015. For AF in ACHD, it was 5,996.4 persons per 100,000 ACHD during the same period, which was higher than that in the general population ( < 0.001). Significantly higher proportion of death (20.9%) occurred in ACHD with AF than without AF (8.3%) ( < 0.001). The adjusted hazard ratio for AF of death in ACHD was 1.39 (95% confidence interval, 1.29-1.50). The ten-year SR of ACHD with AF was 69.7% whereas it was 87.5% in non-AF ( < 0.001).

Conclusion: In ACHD, AF occurs more frequently and has a worse prognosis than seen in the non-valvular general population in Korea. AF is associated with increased death in ACHD, especially with aging.
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http://dx.doi.org/10.3346/jkms.2021.36.e43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850860PMC
February 2021

The Effects of Propofol or Dexmedetomidine Sedation on Postoperative Recovery in Elderly Patients Receiving Lower Limb Surgery under Spinal Anesthesia: A Retrospective Propensity Score-Matched Analysis.

J Clin Med 2021 Jan 3;10(1). Epub 2021 Jan 3.

Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Propofol and dexmedetomidine are the two most popular intravenous sedatives during anesthesia. However, data comparing the effects of these two sedatives during spinal anesthesia on postoperative recovery are still insufficient. We retrospectively analyzed the medical records of patients aged ≥65 years who underwent orthopedic surgery under spinal anesthesia between March 2012 and February 2017. The patients were allocated into two groups according to the intraoperative sedatives: the propofol group and dexmedetomidine group. We analyzed the incidence of postoperative delirium, analgesic requirement, and rescue anti-emetic treatment. A total of 1045 patients were included in the analysis. After propensity score matching with the propofol group, the dexmedetomidine group showed a lower incidence of postoperative delirium (odds ratio, 0.19; 95% CI, 0.07-0.56; = 0.011). Postoperative analgesic and anti-emetic requirement were not significantly different between the two groups ( = 0.156 and 0.245, respectively). Multivariate logistic regression analysis revealed that intraoperative sedation, age, preoperative albumin level, and hip surgery were significantly associated with the incidence of postoperative delirium. This study showed that intraoperative dexmedetomidine sedation under spinal anesthesia during lower limb surgery is associated with a lower incidence of postoperative delirium compared with propofol sedation.
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http://dx.doi.org/10.3390/jcm10010135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796282PMC
January 2021

Histone acylation marks respond to metabolic perturbations and enable cellular adaptation.

Exp Mol Med 2020 12 11;52(12):2005-2019. Epub 2020 Dec 11.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Republic of Korea.

Acetylation is the most studied histone acyl modification and has been recognized as a fundamental player in metabolic gene regulation, whereas other short-chain acyl modifications have only been recently identified, and little is known about their dynamics or molecular functions at the intersection of metabolism and epigenetic gene regulation. In this study, we aimed to understand the link between nonacetyl histone acyl modification, metabolic transcriptional regulation, and cellular adaptation. Using antibodies specific for butyrylated, propionylated, and crotonylated H3K23, we analyzed dynamic changes of H3K23 acylation upon various metabolic challenges. Here, we show that H3K23 modifications were highly responsive and reversibly regulated by nutrient availability. These modifications were commonly downregulated by the depletion of glucose and recovered based on glucose or fatty acid availability. Depletion of metabolic enzymes, namely, ATP citrate lyase, carnitine acetyltransferase, and acetyl-CoA synthetase, which are involved in Ac-CoA synthesis, resulted in global loss of H3K23 butyrylation, crotonylation, propionylation, and acetylation, with a profound impact on gene expression and cellular metabolic states. Our data indicate that Ac-CoA/CoA and central metabolic inputs are important for the maintenance of histone acylation. Additionally, genome-wide analysis revealed that acyl modifications are associated with gene activation. Our study shows that histone acylation acts as an immediate and reversible metabolic sensor enabling cellular adaptation to metabolic stress by reprogramming gene expression.
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http://dx.doi.org/10.1038/s12276-020-00539-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080766PMC
December 2020

The role of F-fluorodeoxyglucose-positron emission tomography/computed tomography in the differential diagnosis of pericardial disease.

Sci Rep 2020 12 9;10(1):21524. Epub 2020 Dec 9.

Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

This study aimed to assess the role of F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in the differential diagnosis of pericardial disease. The diagnosis is often troublesome because pericardial fluid analysis or biopsy does not always provide answers. FDG-PET/CT can visualize both inflammation and malignancy and offers a whole-body assessment. Patients who visited the Pericardial Disease Clinic of Samsung Medical Center with an FDG-PET/CT order code were extracted. Exclusion criteria were as follows: (1) the purpose of the differential diagnosis was not pericardial disease; (2) the patient had a known advanced-stage malignancy; (3) the patient already have confirmative diagnosis using a serology, pericardial effusion analysis or biopsy. The analysis included 107 patients. The most common final diagnosis was idiopathic (n = 46, 43.0%), followed by tuberculosis (n = 30, 28.0%) and neoplastic (n = 11, 10.3%). A maximum standardized uptake value (SUVmax) ≥ 5 typically indicates tuberculosis or neoplastic pericarditis except in just one case of autoimmune pericarditis); especially all of the SUVmax scores ≥ 10 had tuberculosis. The diagnostic yield of pericardial biopsy was very low (10.2%). Interestingly, all of the pericardium with an SUVmax < 4.4 had nondiagnostic results. In contrast, targeted biopsies based on FDG uptake demonstrated a higher diagnostic yield (38.7%) than pericardium. The sensitivity of FDG-PET/CT was 63.6%. The specificity was 71.9%. The positive predictive value was 20.6%. The negative predictive value 94.5%, and the accuracy was 71.0% for excluding malignancy based upon the FDG uptake patterns. It is possible to explore the differential diagnosis in some patients with difficult pericardiocentesis or pericardial biopsy in a noninvasive manner using on the SUVmax or uptake patterns. In addition, the biopsy strategy depending on FDG uptake is helpful to achieve biopsy more safely and with a higher yield. FDG-PET may enhance the diagnostic efficacy in patients with pericardial disease.
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http://dx.doi.org/10.1038/s41598-020-78581-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726568PMC
December 2020

Comparison of global and regional myocardial strains in patients with heart failure with a preserved ejection fraction vs hypertension vs age-matched control.

Cardiovasc Ultrasound 2020 Nov 10;18(1):44. Epub 2020 Nov 10.

Division of Cardiology, Cardiovascular Imaging Center, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Background: With an increasing clinical importance of the treatment of the heart failure (HF) with preserved ejection fraction (HFpEF), it is important to be certain of the diagnosis of HF. We investigated global and regional left ventricular (LV) strains using speckle tracking echocardiography (STE) in patients with HFpEF and compared those parameters with that of patients with hypertension and normal subjects.

Methods: Peak longitudinal, circumferential and radial strains were assessed globally and regionally for each study groups using STE. Diastolic strain rate was also determined.

Results: There were 50 patients in HFpEF group, 56 patients in hypertension group and 46 age-matched normal subjects. In patients with HFpEF, global peak longitudinal, circumferential and radial strain and strain rate were reduced compared to both hypertension patients and normal controls (- 15.5 ± 5.3 vs - 17.7 ± 3.1 and - 19.9 ± 2.0; - 9.7 ± 2.2 vs - 19.3 ± 3.1 and - 20.5 ± 3.3; 17.7 ± 8.2 vs 38.4 ± 12.4 and 43.6 ± 11.9, respectively, P <  0.001, for all). The diagnostic performance of global circumferential strain to predict the HFpEF was greatest among strain parameters (area under the curve = 0.997).

Conclusions: In the speckle tracking echocardiography, impaired peak global strain and homogeneously reduced regional strain was observed in HFpEF patients compared to the hypertension patients and normal subjects in decreasing order. This can provide early information on the initiation of LV deformation of HFpEF in patients with hypertension or normal subjects.
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http://dx.doi.org/10.1186/s12947-020-00223-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653846PMC
November 2020

The incidence and clinical features of PEGylated filgrastim-induced acute aortitis in patients with breast cancer.

Sci Rep 2020 10 29;10(1):18647. Epub 2020 Oct 29.

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Although PEGylated filgrastim-induced aortitis is very rare and unknown clinically, some cases were reported and increasing, especially in breast cancer patients. The present study investigated the prevalence, clinical features and treatment of aortitis induced by PEGylated filgrastim in patients with breast cancer. A total of 2068 consecutive patients who underwent neoadjuvant/adjuvant chemotherapy with PEGylated filgrastim for breast cancer were enrolled. From the medical record, clinical, laboratory, medication, and imaging evaluation findings were collected. PEGylated filgrastim-induced aortitis was established in 0.3% of the study population. Common clinical presentations included extremely high fever and chest/back pain with high levels of inflammatory markers without any signs of infection. Contrast-enhanced computed tomography scans revealed typical enhancing wall thickening and periaortic soft tissue infiltration at various levels of aorta. All patients improved rapidly after treatment with modest doses of prednisolone (0.5 mg/kg/day) without any complications. Clinicians should be aware of aortitis as a possible complication of granulocyte-colony stimulating factor therapy, especially PEGylated filgrastim, given the frequent misdiagnoses in neutropenic patients undergoing chemotherapy.
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http://dx.doi.org/10.1038/s41598-020-75620-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596224PMC
October 2020

2019 Tabletop Exercise for Laboratory Diagnosis and Analyses of Unknown Disease Outbreaks by the Korea Centers for Disease Control and Prevention.

Osong Public Health Res Perspect 2020 Oct;11(5):280-285

Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Korea.

Objectives: The Korea Centers for Disease Control and Prevention has published "A Guideline for Unknown Disease Outbreaks (UDO)." The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future.

Methods: The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced.

Results: Since September 9, 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen.

Conclusion: Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.
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http://dx.doi.org/10.24171/j.phrp.2020.11.5.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577389PMC
October 2020

In vitro toxicity assessment of crosslinking agents used in hyaluronic acid dermal filler.

Toxicol In Vitro 2021 Feb 20;70:105034. Epub 2020 Oct 20.

Toxicology Laboratory, Sanghuh College of Life Science, Konkuk University, Seoul, Republic of Korea. Electronic address:

Hyaluronic acid (HA) dermal fillers are produced by crosslinking HA with agents, such as 1,4-butanediol diglycidyl ether (BDDE) and poly (ethylene glycol) diglycidyl ether (PEGDE) to acquire desired properties. Thus, the safety evaluation of these crosslinkers is needed at the cellular level. In the present study, cell viability, cytotoxicity, membrane integrity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory responses were evaluated in the human keratinocyte cell line, HaCaT and human dermal fibroblast cell line, HDF in response to treatment with the crosslinkers. In both the cell lines, BDDE significantly decreased cell viability at 100-1000 ppm, while PEGDE showed a decrease at 500-1000 ppm. In HaCaT cells, BDDE markedly increased cytotoxicity (lactate dehydrogenase release) at 100-1000 ppm, but PEGDE showed an increase at 500-1000 ppm. Cells treated with BDDE (100 ppm) caused alteration in the integrity of cell membrane and shape. In both the cell lines, BDDE-treated cells showed significantly higher ROS levels and MMP loss than PEGDE-treated cells. Also, BDDE-treated cells exhibited higher COX-2 expression at 100 ppm. Expression of inflammatory cytokines (TNF-α, and IL-1 β) was higher in BDDE-treated cells. Taken together, PEGDE-treated cells showed markedly lower cytotoxicity, ROS production, and inflammatory responses than BDDE-treated cells. Our data suggest that PEGDE is safer than BDDE as a crosslinker in HA dermal fillers.
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http://dx.doi.org/10.1016/j.tiv.2020.105034DOI Listing
February 2021

Clinical implications of exercise-induced regional wall motion abnormalities in significant aortic regurgitation.

Echocardiography 2020 10 2;37(10):1583-1593. Epub 2020 Oct 2.

Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Significant aortic regurgitation (AR) is sometimes accompanied by regional wall motion abnormalities (RWMA) during exercise stress echocardiography. The aim of this study was to estimate the association between RWMA after exercise and in the presence of significant AR in patients with coronary artery disease (CAD) or volume overload and to predict the eventual need for aortic valve replacement (AVR).

Methods And Results: We retrospectively reviewed 182 patients with significant AR who underwent exercise echocardiography. In addition, we investigated patients with AR who underwent coronary angiography (CAG) or coronary computed tomography angiography (CCTA) and were diagnosed with CAD. The presence of RWMA after exercise was defined as newly developed RWMA after exercise and included all changes in wall motion. Patients were divided into two groups according to the presence of RWMA after exercise: the RWMA group (n = 42) and non-RWMA group (n = 140). In the RWMA group, 31 patients (73.8%) underwent coronary artery evaluation by CAG or CCTA. Only two patients in the RWMA group were diagnosed with current CAD and underwent percutaneous coronary intervention. Patients with RWMA were older (61.6 ± 10.8 vs 52.0 ± 13.7 years, P < .001), had more severe AR (54.8% vs 32.9%), and underwent AVR more frequently (40.5% vs 14.3%, P = .001) than patients without RWMA. METs (odds ratio [OR], 0.796; P = .019), difference between rest and postexercise left ventricular end-diastolic volume (OR, 0.967; P = .001), and the difference between pre- and postexercise left ventricular end-systolic volume (OR, 1.113; P < .001) were identified as independent factors associated with RWMA after exercise according to multivariable logistic regression analysis. The majority of wall motion changes were seen in the lateral and inferior segments, and the locations of wall motion changes were relatively consistent with the direction of the AR jet. The relationship between RWMA after exercise and time to AVR was investigated by simple linear regression (hazard ratio [HR], 3.402; P < .001). After adjusting for baseline parameters of diastolic blood pressure, left ventricular end-systolic dimension (LVESD), aorta size, deceleration time, and METs, the presence of RWMA after exercise was not predictive of time to AVR (HR, 1.106; P = .81). On the other hand, without forcible entry of RWMA after exercise, LVESD (HR, 1.119; P < .001) and METs (HR, 0.828; P = .006) independently predicted the eventual need for AVR as an outcome.

Conclusion: The degree of change in wall motion from rest to exercise in those with significant AR was not correlated with CAD, but was correlated with the severity of volume overload and exercise-induced preload changes, as well as the direction of the AR jet. In addition, RWMA after exercise had no role in predicting the need for AVR.
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http://dx.doi.org/10.1111/echo.14855DOI Listing
October 2020

Effect of Anti-Inflammatory Drugs on Clinical Outcomes in Patients With Malignant Pericardial Effusion.

J Am Coll Cardiol 2020 09;76(13):1551-1561

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Pericardiocentesis (PCC) with extended catheter drainage has become a relatively safe procedure to control pericardial effusion (PE), but little is known about long-term outcomes after PCC in malignant PE.

Objectives: This study evaluated the effects of anti-inflammatory agents on long-term outcomes after effective drainage of PE in active cancer patients.

Methods: From May 2007 to December 2018, 445 patients with malignant PE who underwent echocardiography-guided PCC were enrolled. Clinical, laboratory, echocardiographic and procedural findings, and clinical outcome data were collected. Use of anti-inflammatory agents including colchicine, nonsteroidal anti-inflammatory drugs, or steroids after PCC was also analyzed. Colchicine was administered in a dose of 0.6 mg orally, twice a day for 2 months. The primary outcome was defined as a composite of all-cause death and re-PCC or pericardial window operation due to recurred PE.

Results: The procedure was successful in 97.0% of the cases, with 1 procedure-related death. During the follow-up of 2 years, 26.1% of patients developed recurrent PE, and 46.0% developed constrictive pericarditis. The colchicine treatment group showed a significantly lower risk of composite events (adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [CI]: 0.49 to 0.87; p = 0.003) as well as all-cause death (aHR: 0.60; 95% CI: 0.45 to 0.81; p = 0.001) than did the noncolchicine group. On propensity score matching, colchicine after PCC was consistently associated with a lower composite events (aHR: 0.55; 95% CI: 0.37 to 0.82; p = 0.003).

Conclusions: In cancer patients with malignant PE, PCC with extended drainage can be an appropriate therapeutic option and shows low complication rate. Patients receiving colchicine after successful PCC showed significant improvement in clinical outcome.
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http://dx.doi.org/10.1016/j.jacc.2020.08.003DOI Listing
September 2020

The Extent of Late Gadolinium Enhancement Can Predict Adverse Cardiac Outcomes in Patients with Non-Ischemic Cardiomyopathy with Reduced Left Ventricular Ejection Fraction: A Prospective Observational Study.

Korean J Radiol 2021 03 10;22(3):324-333. Epub 2020 Sep 10.

Division of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objective: The clinical course of an individual patient with heart failure is unpredictable with left ventricle ejection fraction (LVEF) only. We aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived myocardial fibrosis extent and to determine the cutoff value for event-free survival in patients with non-ischemic cardiomyopathy (NICM) who had severely reduced LVEF.

Materials And Methods: Our prospective cohort study included 78 NICM patients with significantly reduced LV systolic function (LVEF < 35%). CMR images were analyzed for the presence and extent of late gadolinium enhancement (LGE). The primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, heart transplantation, implantable cardioverter-defibrillator discharge for major arrhythmia, and hospitalization for congestive heart failure within 5 years after enrollment.

Results: A total of 80.8% (n = 63) of enrolled patients had LGE, with the median LVEF of 25.4% (19.8-32.4%). The extent of myocardial scarring was significantly higher in patients who experienced MACE than in those without any cardiac events (22.0 [5.5-46.1] %LV vs. 6.7 [0-17.1] %LV, respectively, = 0.008). During follow-up, 51.4% of patients with LGE ≥ 12.0 %LV experienced MACE, along with 20.9% of those with LGE ≤ 12.0 %LV (log-rank = 0.001). According to multivariate analysis, LGE extent more than 12.0 %LV was independently associated with MACE (adjusted hazard ratio, 6.71; 95% confidence interval, 2.54-17.74; < 0.001).

Conclusion: In NICM patients with significantly reduced LV systolic function, the extent of LGE is a strong predictor for long-term adverse cardiac outcomes. Event-free survival was well discriminated with an LGE cutoff value of 12.0 %LV in these patients.
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http://dx.doi.org/10.3348/kjr.2020.0082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909865PMC
March 2021

Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis.

Heart 2020 12 11;106(23):1824-1831. Epub 2020 Sep 11.

Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Objective: To evaluate whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors and their cardiac tissue distribution profile and anticalcification abilities are associated with risk of aortic stenosis (AS) progression.

Methods: Out of the five different classes of DPP-4 inhibitors, two had relatively favourable heart to plasma concentration ratios and anticalcification ability in murine and in vitro experiments and were thus categorised as 'favourable'. We reviewed the medical records of 212 patients (72±8 years, 111 men) with diabetes and mild-to-moderate AS who underwent echocardiographic follow-up and classified them into those who received favourable DPP-4 inhibitors (n=28, 13%), unfavourable DPP-4 inhibitors (n=69, 33%) and those who did not receive DPP-4 inhibitors (n=115, 54%).

Results: Maximal transaortic velocity (Vmax) increased from 2.9±0.3 to 3.5±0.7 m/s during follow-up (median, 3.7 years), and the changes were not different between DPP-4 users as a whole and non-users (p=0.143). However, the favourable group showed significantly lower Vmax increase than the unfavourable or non-user group (p=0.018). Severe AS progression was less frequent in the favourable group (7.1%) than in the unfavourable (29.0%; p=0.03) or the non-user (29.6%; p=0.01) group. In Cox regression analysis after adjusting for age, baseline renal function and AS severity, the favourable group showed a significantly lower risk of severe AS progression (HR 0.116, 95% CI 0.024 to 0.551, p=0.007).

Conclusions: DPP-4 inhibitors with favourable pharmacokinetic and pharmacodynamic properties were associated with lower risk of AS progression. These results should be considered in the preparation of randomised clinical trials on the repositioning of DPP-4 inhibitors.
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http://dx.doi.org/10.1136/heartjnl-2020-317024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677484PMC
December 2020

Clinical characteristics and long-term outcomes of peripartum takotsubo cardiomyopathy and peripartum cardiomyopathy.

ESC Heart Fail 2020 Sep 8. Epub 2020 Sep 8.

Division of Cardiology, Department of Medicine, Cardiovascular Imaging Center, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.

Aims: Although some peripartum-associated cardiomyopathy patients present with features that are clinically and echocardiographically similar to those of takotsubo cardiomyopathy (TCM), little is known about the diagnosis and clinical course of peripartum TCM.

Methods And Results: In a tertiary hospital in Seoul, Korea, we searched the hospital database to find cardiomyopathy cases that were associated with pregnancy from January 1995 to May 2019. Applying the published diagnostic criteria, we sought peripartum cardiomyopathy (PPCM) and peripartum TCM patients for comparison. Of 31 pregnancy-associated cardiomyopathy patients, 10 cases of peripartum TCM and 21 cases of PPCM were found. Maternal near-miss death was significantly more common in the peripartum TCM group than in the PPCM group (100.0% vs. 57.1%, P = 0.030). Complete recovery was observed with all peripartum TCM cases, while 23.8% of the PPCM cases had residual left ventricular dysfunction. One death and one heart transplantation occurred in the PPCM group, while neither occurred in the peripartum TCM group. There was no difference between the two groups in terms of the rate of major adverse clinical events at 3 years of follow-up [PPCM group: 26.3% (5/19) vs. TCM group: 33.3% (3/9), P = 0.750].

Conclusions: One-third of pregnancy-associated cardiomyopathy patients had peripartum TCM. With contemporary supportive care, both PPCM and peripartum TCM patients had a low mortality rate and excellent long-term outcomes.
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http://dx.doi.org/10.1002/ehf2.12889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754891PMC
September 2020

COVID-19 Public Health Measures During National Assembly Elections of the Republic of Korea.

Osong Public Health Res Perspect 2020 Aug;11(4):158-163

Central Disease Control Headquarters, Korea Centers for Disease Control and Prevention, Cheongju, Korea.

The general elections for the 21 National Assembly in the Republic of Korea were scheduled for April 15, 2020, which was during the novel coronavirus disease (COVID-19) outbreak. To ensure a safe election, the Korean Centers for Disease Control and Prevention (KCDC) recommended several public health measures. The KCDC developed key interventions after reviewing the general election strategy that targeted COVID-19 patients and individuals isolating at home. Four voters who participated in the election tested positive, but did not contract COVID-19 during voting. The results demonstrated that the KCDC minimized the spread of infection in the community during the election. The measures implemented by KCDC during the election held under a COVID-19 outbreak cannot be generalized to elections as a whole because cultural and national consciousness vary between countries. Nevertheless, it demonstrates that the systemic strategies and applications against the pandemic can minimize the possibility of viral spread.
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http://dx.doi.org/10.24171/j.phrp.2020.11.4.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442438PMC
August 2020

Diffuse Myocardial Fibrosis and Diastolic Function in Aortic Stenosis.

JACC Cardiovasc Imaging 2020 12 19;13(12):2561-2572. Epub 2020 Aug 19.

Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. Electronic address:

Objectives: The aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS).

Background: Myocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS.

Methods: Patients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation.

Results: Patients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e' <7 cm/s) and increased LV filling pressure (E/e' ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e' and higher E/septal e' ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function.

Conclusions: Diffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis.
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http://dx.doi.org/10.1016/j.jcmg.2020.07.007DOI Listing
December 2020

Insulin synthesized in the paraventricular nucleus of the hypothalamus regulates pituitary growth hormone production.

JCI Insight 2020 08 20;5(16). Epub 2020 Aug 20.

Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, South Korea.

Evidence has mounted that insulin can be synthesized in various brain regions, including the hypothalamus. However, the distribution and functions of insulin-expressing cells in the hypothalamus remain elusive. Herein, we show that in the mouse hypothalamus, the perikarya of insulin-positive neurons are located in the paraventricular nucleus (PVN) and their axons project to the median eminence; these findings define parvocellular neurosecretory PVN insulin neurons. Contrary to corticotropin-releasing hormone expression, insulin expression in the PVN was inhibited by restraint stress (RS) in both adult and young mice. Acute RS-induced inhibition of PVN insulin expression in adult mice decreased both pituitary growth hormone (Gh) mRNA level and serum GH concentration, which were attenuated by overexpression of PVN insulin. Notably, PVN insulin knockdown or chronic RS in young mice hindered normal growth via the downregulation of GH gene expression and secretion, whereas PVN insulin overexpression in young mice prevented chronic RS-induced growth retardation by elevating GH production. Our results suggest that in both normal and stressful conditions, insulin synthesized in the parvocellular PVN neurons plays an important role in the regulation of pituitary GH production and body length, unveiling a physiological function of brain-derived insulin.
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http://dx.doi.org/10.1172/jci.insight.135412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455129PMC
August 2020

The Long-term Effectiveness of the Automatic Position-Adaptive System in Spinal Cord Stimulation: A Retrospective Comparative Study with a Two-Year Follow-up.

Pain Med 2020 10;21(10):2288-2297

Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: To compare the nonadaptive manual system with the position-adaptive system in subjects with permanent spinal cord stimulator (SCS) implantation over a two-year follow-up period.

Design: Retrospective study.

Setting: Tertiary university-based national hospital.

Subjects: Patients who underwent permanent SCS implantation procedures.

Methods: Patients were divided into an adaptive group and a nonadaptive group according to the type of implanted SCS device. The primary outcome was the change (%) in pain intensity from baseline between the adaptive and nonadaptive groups at 24 months after SCS implantation. The secondary outcomes were comparisons of detailed clinical variables such as the scores of patient pain and satisfaction during the two-year follow-up after SCS therapy. Further, the number of subjects with SCS removal or revision within two years after SCS implantation was investigated.

Results: Of 187 patients with permanent SCS implantation, 85 in the nonadaptive group and 64 in the position-adaptive group were finally analyzed. The reduction in pain intensity at 24 months was higher in the adaptive group (-38.6%) than in the nonadaptive group (-30.8%, P = 0.05). Similarly, patient satisfaction with the SCS treatment at 24 months was superior in the adaptive group than in the nonadaptive group (85.7% vs 67.5% were satisfied in each group, respectively, P = 0.024). During the two years, 5.3% of patients (N = 10) underwent SCS removal and 7.0% (N = 13) underwent revision procedures.

Conclusions: There was a trend of a sustained reduction in pain intensity as well as improvement in patient satisfaction at two-year follow-up in the position-adaptive system, suggesting long-term benefit over the nonadaptive manual system during SCS treatment.
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http://dx.doi.org/10.1093/pm/pnaa121DOI Listing
October 2020
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