Publications by authors named "Sang-Eun Lee"

730 Publications

Atherogenic index of plasma and the risk of rapid progression of coronary atherosclerosis beyond traditional risk factors.

Atherosclerosis 2021 Mar 13;324:46-51. Epub 2021 Mar 13.

Department of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea; Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea. Electronic address:

Background And Aims: The atherogenic index of plasma (AIP) has been suggested as a marker of plasma atherogenicity. This study aimed to assess the association between AIP and the rapid progression of coronary atherosclerosis using serial coronary computed tomography angiography (CCTA).

Methods: A total of 1488 adults (60.9 ± 9.2 years, 58.9% male) who underwent serial CCTA with a median inter-scan period of 3.4 years were included. AIP was defined as the base 10 logarithm of the ratio of the concentrations of triglyceride to high-density lipoprotein cholesterol. Rapid plaque progression (RPP) was defined as the change of percentage atheroma volume (PAV) ≥1.0%/year. All participants were divided into three groups based on AIP tertiles.

Results: Baseline total PAV (median [interquartile range (IQR)]) (%) (group I [lowest]: 1.91 [0.00, 6.21] vs. group II: 2.82 [0.27, 8.83] vs. group III [highest]: 2.70 [0.41, 7.50]), the annual change of total PAV (median [IQR]) (%/year) (group I: 0.27 [0.00, 0.81] vs. group II: 0.37 [0.04, 1.11] vs. group III: 0.45 [0.06, 1.25]), and the incidence of RPP (group I: 19.7% vs. group II: 27.3% vs. group III: 31.4%) were significantly different among AIP tertiles (all p < 0.05). In multiple logistic regression analysis, the risk of RPP was increased in group III (odds ratio: 1.52, 95% confidence interval: 1.02-2.26; p = 0.042) compared to group I after adjusting for clinical factors and baseline total PAV.

Conclusions: Based on serial CCTA findings, AIP is an independent predictive marker for RPP beyond traditional risk factors.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.009DOI Listing
March 2021

Flavisolibacter longurius sp. nov., isolated from soil.

Arch Microbiol 2021 Mar 20. Epub 2021 Mar 20.

Department of Bio and Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 139-774, Korea.

A novel Gram-negative bacterial strain BT320 was isolated from soil collected in Uijeongbu city, Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain BT320 belong to a distinct lineage within the genus Flavisolibacter (family Chitinophagaceae, order Chitinophagales, class Chitinophagia). The strain BT320 was closely related to Flavisolibacter galbus 17J28-26 (97.6% 16S rRNA gene similarity), Flavisolibacter nicotianae X7X (96.7%), Flavisolibacter ginsengiterrae Gsoil 492 (96.2%), and Flavisolibacter ginsengisoli Gsoil 643 (96.1%). The genome size of strain BT320 was 5,664,094 bp. Bacterial growth was observed at 10-37 °C (optimum 25 °C) and pH 6.0-8.0 (optimum pH 7.0) on R2A agar. The major cellular fatty acids of strain BT320 were iso-C, summed feature 3 (C ω6c/C ω7c), and summed feature 1 (iso-C H/C 3OH). Its predominant respiratory quinone was MK-7. The major polar lipid of strain BT320 was identified to be phosphatidylethanolamine (PE). Based on the biochemical, chemotaxonomic, and phylogenetic analysis, strain BT320 can be suggested as a novel bacterial species within the genus Flavisolibacter and the proposed name is Flavisolibacter longurius. The type strain of Flavisolibacter longurius is BT320 (= KCTC 72422 = NBRC 114375).
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http://dx.doi.org/10.1007/s00203-021-02236-3DOI Listing
March 2021

Development and Validation of a Deep Learning Based Diabetes Prediction System Using a Nationwide Population-Based Cohort.

Diabetes Metab J 2021 Feb 25. Epub 2021 Feb 25.

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Korea.

Background: Previously developed prediction models for type 2 diabetes mellitus (T2DM) have limited performance. We developed a deep learning (DL) based model using a cohort representative of the Korean population.

Methods: This study was conducted on the basis of the National Health Insurance Service-Health Screening (NHIS-HEALS) cohort of Korea. Overall, 335,302 subjects without T2DM at baseline were included. We developed the model based on 80% of the subjects, and verified the power in the remainder. Predictive models for T2DM were constructed using the recurrent neural network long short-term memory (RNN-LSTM) network and the Cox longitudinal summary model. The performance of both models over a 10-year period was compared using a time dependent area under the curve.

Results: During a mean follow-up of 10.4±1.7 years, the mean frequency of periodic health check-ups was 2.9±1.0 per subject. During the observation period, T2DM was newly observed in 8.7% of the subjects. The annual performance of the model created using the RNN-LSTM network was superior to that of the Cox model, and the risk factors for T2DM, derived using the two models were similar; however, certain results differed.

Conclusion: The DL-based T2DM prediction model, constructed using a cohort representative of the population, performs better than the conventional model. After pilot tests, this model will be provided to all Korean national health screening recipients in the future.
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http://dx.doi.org/10.4093/dmj.2020.0081DOI Listing
February 2021

Total Synthesis of Hinckdentine A.

Org Lett 2021 Mar 25;23(6):2169-2173. Epub 2021 Feb 25.

Department of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.

The total synthesis of (±)-hinckdentine A is described herein. A cyanide-catalyzed imino-Stetter reaction of the aldimine derived from ethyl 2-amino-3,5-dibromocinnamate and 5-bromo-2-nitrobenzaldehyde followed by oxidative rearrangement afforded a 2,2-disubstituted 3-indolinone derivative containing the carbon skeleton and all of the functional groups present in the natural product correctly positioned, including three bromine atoms. Subsequent D-ring formation and seven-membered C-ring construction completed the total synthesis of hinckdentine A.
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http://dx.doi.org/10.1021/acs.orglett.1c00323DOI Listing
March 2021

The Relationship between the Timing of Sugammadex Administration and the Upper Airway Obstruction during Awakening from Anesthesia: A Retrospective Study.

Medicina (Kaunas) 2021 Jan 21;57(2). Epub 2021 Jan 21.

Department of Anesthesiology and Pain Medicine, Haeundae Paik Hospital of Inje University, 875 Haeun-daero, Haeundae-gu, Busan KS012, Korea.

: The harmonization of recovery of consciousness and muscular function is important in emergence from anesthesia. Even if muscular function is recovered, tracheal extubation without adequate recovery of consciousness may increase the risk of respiratory complications. In particular, upper airway obstruction is one of the common respiratory complications and can sometimes be fatal. However, the association between the timing of sugammadex administration and the upper airway obstruction that can occur during awakening from anesthesia has rarely been studied. : The medical records of 456 patients who had surgery under general endotracheal anesthesia (GETA) at the Haeundae Paik Hospital between October 2017 and July 2018 and who received intravenous sugammadex to reverse rocuronium-induced neuromuscular blockade were analyzed. The correlations between bispectral index (BIS) and minimum alveolar concentration (MAC) at the time of sugammadex administration, the incidence of complications, and the time to tracheal extubation were analyzed to investigate how different timings of sugammadex administration affected upper airway obstruction after tracheal extubation. : The effect of BIS and the duration from anesthetic discontinuation to sugammadex administration on upper airway obstruction was not statistically significant. However, the odds ratio of complication rates with MAC < 0.3 compared with MAC ≥ 0.3 was 0.40 (95% confidence interval 0.20 to 0.81, = 0.011), showing a statistically significant increase in risk with MAC ≥ 0.3 for upper airway obstruction.
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http://dx.doi.org/10.3390/medicina57020088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909768PMC
January 2021

Intravenous allogeneic umbilical cord blood-derived mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa patients.

JCI Insight 2021 Jan 25;6(2). Epub 2021 Jan 25.

Department of Dermatology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea.

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease that causes severe mucocutaneous fragility due to mutations in COL7A1 (encoding type VII collagen [C7]). In this phase I/IIa trial, we evaluated the safety and possible clinical efficacy of intravenous infusion of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in patients with RDEB.METHODSFour adult and two pediatric patients with RDEB were treated with 3 intravenous injections of hUCB-MSCs (1 × 106 to 3 × 106 cells/kg) every 2 weeks and followed up for 8-24 months after treatment. The primary endpoint was safety. Secondary endpoints related to efficacy included clinical parameters, such as disease severity score, wound assessment, itch and pain score, and quality of life. C7 expression levels and inflammatory infiltrates in the skin, as well as serum levels of inflammatory markers and neuropeptides, were also assessed.RESULTSIntravenous hUCB-MSC infusions were well tolerated, without serious adverse events. Improvements in the Birmingham Epidermolysis Bullosa Severity Score, body surface area involvement, blister counts, pain, pruritus, and quality of life were observed with maximal effects at 56-112 days after treatment. hUCB-MSC administration induced M2 macrophage polarization and reduced mast cell infiltration in RDEB skin. Serum levels of substance P were decreased after therapy. Increased C7 expression was observed at the dermoepidermal junction in 1 of 6 patients at day 56.CONCLUSIONTo the best of our knowledge, this is the first clinical trial of systemic administration of allogeneic hUCB-MSCs in patients with RDEB, demonstrating safety and transient clinical benefits.TRIAL REGISTRATIONClinicalTrials.gov NCT04520022.FUNDINGThis work was supported by Daewoong Pharmaceutical Co. Ltd. and Kangstem Biotech Co. Ltd.
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http://dx.doi.org/10.1172/jci.insight.143606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934866PMC
January 2021

Signal detection of botulinum toxin type A (BoNT/A) using the Korea Adverse Event Reporting System Database, 1999 - 2016.

Int J Clin Pharmacol Ther 2021 Jan 22. Epub 2021 Jan 22.

Objective: To detect signals of potential adverse events (AEs) after botulinum toxin (BTX) treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD).

Materials And Methods: The individual case safety reports (ICSRs) submitted to KIDS-KD from 1999 to 2016 were analyzed. To detect safety signals, disproportionality analysis was introduced, and the three indices (proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC)) were calculated based on the reported preferred terms (WHO-ART, preferred term (PT)). The signals detected were compared with drug labels from Korea and the USA.

Results: A total of 5,896 AE reports were collected in January 1999 - December 2016 in the Korea Adverse Event Reporting System (KAERS) databases. Among the total of 103,785 drug-AE pairs, 1,413 were attributed to BTX. The disproportionality analysis produced 44 PTs as safety signals and detected 7 unlabeled PTs that were not listed on the labels. After matching for age and sex (1 : 2), the adjusted ROR of ineffective medicine and depression in BTX was 21.60 (95% confidence interval (CI), 19.12 - 24.41) and 6.02 (95% CI, 3.41 - 10.64) respectively.

Conclusion: The number of AE reports after BTX has increased, the majority of which were from females. Safety signals such as "medicine ineffective" and "concentration impaired" may be due to increasing off-label use, which warrants long-term surveillance, especially among females after BTX injection.
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http://dx.doi.org/10.5414/CP203776DOI Listing
January 2021

Eosinophilic Myocarditis Progresses to Giant Cell Myocarditis Requiring Heart Transplantation: A Case Report.

Allergy Asthma Immunol Res 2021 Mar;13(2):353-355

Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4168/aair.2021.13.2.353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840877PMC
March 2021

Severe Atrophy of the Ipsilateral Psoas Muscle Associated with Hip Osteoarthritis and Spinal Stenosis-A Case Report.

Medicina (Kaunas) 2021 Jan 15;57(1). Epub 2021 Jan 15.

Department of Anesthesia & Pain Medicine, Inje University Haeundae Paik Hospital, Busan 612-896, Korea.

Pathology of the lumbar spine and hip joint can commonly coexist in the elderly. Anterior and lateral leg pain as symptoms of hip osteoarthritis and spinal stenosis can closely resemble each other, with only subtle differences in both history and physical examinations. It is not easy to identify the origin of this kind of hip pain. The possibility of hip osteoarthritis should not be underestimated, as this could lead to an incorrect diagnosis and inappropriate spinal surgery. We report the case of a 54-year-old female with chronic right anterior and lateral leg pain who did not respond to repeated spinal blocks based on lumbar MRI, but in whom hip osteoarthritis was considered since severe atrophy of the ipsilateral psoas muscle was identified. We suggest that severe psoas muscle atrophy can be a clinical clue to identify hip osteoarthritis and is related to lower extremity pain, even if there is a coexisting lumbar spine pathology.
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http://dx.doi.org/10.3390/medicina57010073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830484PMC
January 2021

Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis.

JACC Cardiovasc Imaging 2021 Jan 13. Epub 2021 Jan 13.

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea; Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Objectives: This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).

Background: Coronary CTA can noninvasively assess coronary plaques quantitatively.

Methods: Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.

Results: Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm [interquartile range (IQR): 0.0 to 39.6 mm]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm [IQR: 0.0 to 127.4 mm]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm [IQR: 96.7 to 306.4 mm]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.

Conclusions: The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).
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http://dx.doi.org/10.1016/j.jcmg.2020.11.009DOI Listing
January 2021

Progression of whole-heart Atherosclerosis by coronary CT and major adverse cardiovascular events.

J Cardiovasc Comput Tomogr 2021 Jan 1. Epub 2021 Jan 1.

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Background: The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE).

Methods: The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted.

Results: The study population comprised 1166 patients (age 60.5 ​± ​9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P ​< ​0.001.

Conclusions: Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year.
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http://dx.doi.org/10.1016/j.jcct.2020.12.007DOI Listing
January 2021

Pseudocnuella soli gen. nov., sp. nov., a bacterium from soil belonging to the family Chitinophagaceae.

Antonie Van Leeuwenhoek 2021 Feb 15;114(2):161-168. Epub 2021 Jan 15.

Department of Bio & Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 139-774, Republic of Korea.

A Gram-stain negative, aerobic, rod-shaped, yellow-coloured bacterium, designated strain 17J28-1, was isolated from soil of Jeju Island, Korea. Optimal growth was found to occur at 30 °C, at pH 6.0 and in the absence of NaCl on R2A at 30 °C. Strain 17J28-1 showed resistance to UV-radiation. The draft genome sequence of strain 17J28-1 is 4804,510 bp long with a 49.4% G + C content. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain 17J28-1 forms a distinct lineage within the family Chitinophagaceae (order Chitinophagales, class Chitinophagia) and is closely related to Cnuella takakiae (93.7% 16S rRNA gene sequence similarity) and Flavisolibacter ginsengiterrae (93.1%). In addition, genomic comparison using digital DNA-DNA hybridization (dDDH) and OrthoANI analyses between the novel organism and the members of the family Chitinophagaceae revealed identities of 65.5-74.1% and 18.1-28%, respectively. The predominant cellular fatty acids were identified as C iso, C iso G and C iso 3-OH and the major respiratory quinone as MK-7. Based on these data we propose that strain 17J28-1 (= KCTC 62223 = JCM 33202) represents a novel genus and species in the family Chitinophagaceae, for which the name Pseudocnuella soli gen. nov. sp. nov. is proposed.
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http://dx.doi.org/10.1007/s10482-020-01509-zDOI Listing
February 2021

Cooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells.

Nat Commun 2021 01 11;12(1):263. Epub 2021 Jan 11.

Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea.

Clusters of tightly packed synaptic vesicles (SVs) are a defining feature of nerve terminals. While SVs are mobile within the clusters, the clusters have no boundaries consistent with a liquid phase. We previously found that purified synapsin, a peripheral SV protein, can assemble into liquid condensates and trap liposomes into them. How this finding relates to the physiological formation of SV clusters in living cells remains unclear. Here, we report that synapsin alone, when expressed in fibroblasts, has a diffuse cytosolic distribution. However, when expressed together with synaptophysin, an integral SV membrane protein previously shown to be localized on small synaptic-like microvesicles when expressed in non-neuronal cells, is sufficient to organize such vesicles in clusters highly reminiscent of SV clusters and with liquid-like properties. This minimal reconstitution system can be a powerful model to gain mechanistic insight into the assembly of structures which are of fundamental importance in synaptic transmission.
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http://dx.doi.org/10.1038/s41467-020-20462-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801664PMC
January 2021

Risk Factors of Clonorchis sinensis Human Infections in Endemic Areas, Haman-Gun, Republic of Korea: A Case-Control Study.

Korean J Parasitol 2020 Dec 29;58(6):647-652. Epub 2020 Dec 29.

Division of Vectors and Parasitic Diseases, Korea Disease Control and Prevention Agency, Cheongju 28159, Korea.

Clonorchis sinensis is the most common fish-borne intestinal parasite in Korea. The aim of the present investigation was to survey the status of C. sinensis infection and analyze associated risk factors in residents of Haman-gun, Gyeongsangnam-do. A total of 5,114 residents from 10 administrative towns/villages voluntarily agreed to participate in the study, which comprised fecal examination, a questionnaire survey for risk factors, ultrasonography, and enzymelinked immunosorbent assay for cancer biomarker detection in the blood. We detected C. sinensis eggs in 5.3% of the subjects. By region, Gunbuk-myeon had the highest number of residents with C. sinensis eggs. The infection rate and intensity were higher in male than in female residents. Based on the risk factor questionnaire, infection was highly associated with drinking, a history of C. sinensis infection, and the practice of eating of raw freshwater fish. Extension of the bile duct, infection intensity, and cancer biomarker detection significantly correlated with the presence of eggs in the study population. In conclusion, the development of feasible, long-term control policies and strategies for the elimination of C. sinensis in Korea is still required.
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http://dx.doi.org/10.3347/kjp.2020.58.6.647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806425PMC
December 2020

Surveillance on the Vivax Malaria in Endemic Areas in the Republic of Korea Based on Molecular and Serological Analyses.

Korean J Parasitol 2020 Dec 29;58(6):609-617. Epub 2020 Dec 29.

Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.

Plasmodium vivax reemerged in 1993. It has been sustained for more than 25 years and become one of the important indigenous parasitic diseases in northern and western parts of the Republic of Korea near the demilitarized zone. In particular, relapse is a significant concern for the control of malaria, as short- and long-term incubation periods vary among those infected in Korea. In this study, the prevalence of asymptomatic carriers was examined among residents of high endemic areas of vivax malaria during nonseasonal transmission of mosquitoes. Blood samples from 3 endemic regions in northwestern Korea were evaluated by microscopic examination, rapid diagnostic testing, and nested PCR to identify asymptomatic patients carrying malaria parasites in the community. However, no positive malaria case among residents of endemic areas was detected. Additionally, serological analysis was carried out to measure antibodies against 3 antigenic recombinant proteins of P. vivax, merozoite surface protein 1-19, circumsporozoite surface protein-VK210, and liver-stage antigen (PvLSA-N), by the protein array method. Interestingly, seropositivity of sera between previous exposure and samples without exposure to malaria was significantly higher using the PvLSA-N antigen than the other antigens, suggesting that PvLSA-N can be used as a serological marker to analyze the degree of exposure for malaria transmission in endemic areas. This indicates a very low asymptomatic carrier prevalence during the nonmalaria season in the endemic areas of Korea.
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http://dx.doi.org/10.3347/kjp.2020.58.6.609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806437PMC
December 2020

Flaviaesturariibacter aridisoli sp. nov., A Bacterium Isolated from Dry Soil.

Curr Microbiol 2021 Feb 4;78(2):837-842. Epub 2021 Jan 4.

Department of Bio & Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 139-774, Korea.

A novel bacterial strain, designated 17J68-15, was isolated from dry soil collected in Jeju Island, South Korea. Cells of strain 17J68-15 are Gram-negative, pale-yellow-colored, non-motile, non-spore-forming, rod-shaped was able to grow at 18-42 °C with 0-1% NaCl on R2A agar. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the strain was distinct from any previously known species of the genus Flaviaesturariibacter. The highest degrees of 16S rRNA gene sequence similarity found with Flaviaesturariibacter terrae HY03 (97.6%), Flaviaesturariibacter amylovorans (96.2%) and Flaviaesturariibacter luteus AW305 (96.0%). The DNA G + C content of the novel strain, 17J68-15, was 9.3 mol%. Chemotaxonomic data revealed that the major fatty acids were iso-C, iso-C G, iso-C 3-OH and summed feature 3 (C ω6c and/or C ω7c); the major polar lipid was identified as phosphatidylethanolamine, and the major quinone was identified as MK-7. Based on polyphasic characterization, strain 17J68-15 represents a novel species of the genus Flaviaesturariibacter for which the name Flaviaesturariibacter aridisoli sp. nov. is proposed, with the type strain 17J68-15 (= KCTC 62220 = JCM 19635).
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http://dx.doi.org/10.1007/s00284-020-02312-9DOI Listing
February 2021

Evaluation of Contrast Flow Patterns with Cervical Interlaminar Epidural Injection: Comparison of Midline and Paramedian Approaches.

Medicina (Kaunas) 2020 Dec 24;57(1). Epub 2020 Dec 24.

Department of Anesthesia & Pain Medicine, Inje University Haeundae Paik Hospital, Busan 612-896, Korea.

The purpose of this study was to compare and to analyze contrast spread patterns between the paramedian and midline approaches to cervical interlaminar epidural injection (CIEI). We retrospectively enrolled 84 CIEI cases that had been performed for unilateral cervical spinal pain from April 2019 to April 2020. After 3 mL of contrast had been injected into the epidural space, fluoroscopic images were obtained. The CIEI was divided into a midline (Group M, = 42) and a paramedian (Group P, = 42) approach by anteroposterior imaging. The P Group was classified into a more medial (Group Pm, = 26) and a more lateral (Group Pl, = 16) group. Using ImageJ on an anteroposterior image, we assessed the grayscale brightness ratio of the ipsilateral or contralateral side of the vertebral body as well as the intervertebral disc space one level just above the needle location. We identified the dispersion of contrast into the ventral epidural space. : The grayscale brightness ratio was significantly higher in Group P than in Group M ( < 0.001). The incidence of ventral epidural spread in Group M was 57.1% versus 88.1% in Group P, which was significantly different ( = 0.001). The fluoroscopic CIEI finding in the paramedian approach predominantly showed an excellent delivery of the injectate to the ipsilateral side in comparison to the contralateral side. This showed a greater advantage in delivery toward ventral epidural space as compared to the midline approach.
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http://dx.doi.org/10.3390/medicina57010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823639PMC
December 2020

SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses.

Proc Natl Acad Sci U S A 2021 Jan;118(2)

Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea;

Glutamate uptake into synaptic vesicles (SVs) depends on cation/H exchange activity, which converts the chemical gradient (ΔpH) into membrane potential (Δψ) across the SV membrane at the presynaptic terminals. Thus, the proper recruitment of cation/H exchanger to SVs is important in determining glutamate quantal size, yet little is known about its localization mechanism. Here, we found that secretory carrier membrane protein 5 (SCAMP5) interacted with the cation/H exchanger NHE6, and this interaction regulated NHE6 recruitment to glutamatergic presynaptic terminals. Protein-protein interaction analysis with truncated constructs revealed that the 2/3 loop domain of SCAMP5 is directly associated with the C-terminal region of NHE6. The use of optical imaging and electrophysiological recording showed that small hairpin RNA-mediated knockdown (KD) of SCAMP5 or perturbation of SCAMP5/NHE6 interaction markedly inhibited axonal trafficking and the presynaptic localization of NHE6, leading to hyperacidification of SVs and a reduction in the quantal size of glutamate release. Knockout of NHE6 occluded the effect of SCAMP5 KD without causing additional defects. Together, our results reveal that as a key regulator of axonal trafficking and synaptic localization of NHE6, SCAMP5 could adjust presynaptic strength by regulating quantal size at glutamatergic synapses. Since both proteins are autism candidate genes, the reduced quantal size by interrupting their interaction may underscore synaptic dysfunction observed in autism.
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http://dx.doi.org/10.1073/pnas.2011371118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812776PMC
January 2021

Correction to: Pontibacter fetidus sp. nov. and Pontibacter burrus sp. nov., isolated from the soil.

Arch Microbiol 2020 Dec 26. Epub 2020 Dec 26.

Department of Bio and Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 139-774, Republic of Korea.

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http://dx.doi.org/10.1007/s00203-020-02132-2DOI Listing
December 2020

Characteristics of secondary epiretinal membrane due to peripheral break.

Sci Rep 2020 11 30;10(1):20881. Epub 2020 Nov 30.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

This study aimed to investigate morphological differences between idiopathic epiretinal membrane (ERM) and secondary ERM due to peripheral break (SEPB) and to identify clinical characteristics in eyes with SEPB to facilitate peripheral retinal examination. The retrospective cross-sectional study involved 93 consecutive eyes in 91 patients who underwent ERM removal surgery. Eyes were divided into two groups: the macular pucker group and the idiopathic ERM group. En-face Optical Coherence Tomography (OCT) images, fundus photographs, severity of metamorphopsia (M-score) and clinical characteristics of each group were compared. ERM extent and eccentricity (ratio of the shortest and longest distances from the foveal center to the boundary) were obtained through en-face OCT imaging. Fundus photographs were used to judge whether the membrane was turbid or not. Patients with SEPB were younger than patients with idiopathic ERM (61.3 ± 7.5 vs. 66.6 ± 8.3 years; p < 0.05). Preoperative M-score and myopic refractive error, axial length were also significantly higher in the macular pucker group than in the idiopathic ERM group (all p < 0.05). There was no difference in ERM extent between the two groups. The incidence of ERM eccentricity was 23 of the 34 eyes (67.6%) in the SEPB group and 26 of the 59 eyes (44.1%) in the idiopathic ERM group (p < 0.05). The incidence of turbid ERM was 18 of the 34 eyes (52.9%) in the SEPB group and 10 of the 59 eyes (16.9%) in the idiopathic ERM group (p < 0.01). The SEPB group, compared with the idiopathic ERM group, tended to have eccentric, turbid ERM at a younger age and with more severe metamorphopsia and myopic refractive error.
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http://dx.doi.org/10.1038/s41598-020-78093-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705695PMC
November 2020

The Relationship Between Coronary Calcification and the Natural History of Coronary Artery Disease.

JACC Cardiovasc Imaging 2021 Jan 18;14(1):233-242. Epub 2020 Nov 18.

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea; Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Centre, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Objectives: The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.

Background: Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.

Methods: This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques).

Results: CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis.

Conclusions: Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).
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http://dx.doi.org/10.1016/j.jcmg.2020.08.036DOI Listing
January 2021

Comparative differences in the atherosclerotic disease burden between the epicardial coronary arteries: quantitative plaque analysis on coronary computed tomography angiography.

Eur Heart J Cardiovasc Imaging 2021 Feb;22(3):322-330

Department of Radiology, Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY, USA.

Aims: Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries.

Methods And Results: A total of 1271 patients (age 60 ± 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 ± 29.4 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; P < 0.001), even when correcting for vessel length or volume. The prevalence of ≥2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P < 0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P < 0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001).

Conclusion: Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries.
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http://dx.doi.org/10.1093/ehjci/jeaa275DOI Listing
February 2021

Role of 11β-hydroxysteroid dehydrogenase type 1 in the development of atopic dermatitis.

Sci Rep 2020 11 19;10(1):20237. Epub 2020 Nov 19.

Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.

Glucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic-pituitary-adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), including the skin. The inactive GC cortisone is converted by 11β-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11β-HSD1 in inflammation is unclear. We assessed whether 11β-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11β-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11β-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11β-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11β-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11β-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.
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http://dx.doi.org/10.1038/s41598-020-77281-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678864PMC
November 2020

Outbreak of Cyclosporiasis in Korean Travelers Returning from Nepal.

Korean J Parasitol 2020 Oct 22;58(5):589-592. Epub 2020 Oct 22.

Division of Vectors & Parasitic Diseases, Korea Disease Control and Prevention Agency, Cheongju 28159, Korea.

Cyclospora cayetanensis is an apicomplexan protozoan and is one of the most common pathogens causing chronic diarrhea worldwide. Eight stool samples with diarrheal symptom out of 18 Korean residents who traveled to Nepal were obtained, and examined for 25 enteropathogens including 16 bacterial species, 5 viral species, and 4 protozoans in stool samples as causative agents of water-borne and food-borne disease. Only C. cayetanensis was detected by nested PCR, and 3 PCR-positive samples were sequenced to confirm species identification. However, the oocysts of C. cayetanensis in fecal samples could not be detected by direct microscopy of the stained sample. As far as we know, this is the first report of a group infection with C. cayetanensis from a traveler visiting Nepal, and the second report of a traveler's diarrhea by C. cayetanensis imported in Korea.
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http://dx.doi.org/10.3347/kjp.2020.58.5.589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672228PMC
October 2020

Spirosoma aureum sp. nov., and Hymenobacter russus sp. nov., radiation-resistant bacteria in Cytophagales order isolated from soil.

Antonie Van Leeuwenhoek 2020 Dec 4;113(12):2201-2212. Epub 2020 Nov 4.

Department of Bio and Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 01797, Korea.

A Gram-stain-negative, aerobic, nonmotile, yellow-colored strain BT328 and Gram-stain-negative, aerobic, non-motile, red-colored strain BT18 were isolated from the soil collected in Korea. Phylogenetic analyses based on 16S rRNA gene sequence revealed that strain BT328 formed a distinct lineage within the family Spirosomaceae (order Cytophagales, class Cytophagia) and was most closely related to a member of the genus Spirosoma, Spirosoma terrae 15J9-4 (95.9% 16S rRNA gene sequence similarity). Optimal growth occurred at 25 °C, pH 7.0 and in the absence of NaCl. The predominant cellular fatty acids were summed feature 3 (C ω6c/C ω7c) and C ω5c. The major respiratory quinone was MK-7. The major polar lipid was phosphatidylethanolamine. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain BT18 formed a distinct lineage within the family Hymenobacteraceae (order Cytophagales, class Cytophagia, phylum Bacteroidetes) and was most closely related to members of the genus Hymenobacter, Hymenobacter knuensis 16F7C-2 (97.0% 16S rRNA gene sequence similarity). Optimal growth occurred at 25 °C and pH 7.0 without NaCl. The major fatty acids were iso-C and anteiso-C. The major menaquinone was MK-7. The major polar lipid was phosphatidylethanolamine. Biochemical, chemotaxonomic and phylogenetic analyses indicated that strains BT328 and BT18 represents a novel bacterial species within the genus Spirosoma and Hymenobacter, respectively. For which the name Spirosoma aureum and Hymenobacter russus is proposed. The type strain of S. aureum is BT328 (=KCTC 72365 = NBRC 114506) and the type strain of H. russus is BT18 (=KCTC 62610 = NBRC 114380).
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http://dx.doi.org/10.1007/s10482-020-01492-5DOI Listing
December 2020

Spirosoma aureum sp. nov., and Hymenobacter russus sp. nov., radiation-resistant bacteria in Cytophagales order isolated from soil.

Antonie Van Leeuwenhoek 2020 Dec 4;113(12):2201-2212. Epub 2020 Nov 4.

Department of Bio and Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 01797, Korea.

A Gram-stain-negative, aerobic, nonmotile, yellow-colored strain BT328 and Gram-stain-negative, aerobic, non-motile, red-colored strain BT18 were isolated from the soil collected in Korea. Phylogenetic analyses based on 16S rRNA gene sequence revealed that strain BT328 formed a distinct lineage within the family Spirosomaceae (order Cytophagales, class Cytophagia) and was most closely related to a member of the genus Spirosoma, Spirosoma terrae 15J9-4 (95.9% 16S rRNA gene sequence similarity). Optimal growth occurred at 25 °C, pH 7.0 and in the absence of NaCl. The predominant cellular fatty acids were summed feature 3 (C ω6c/C ω7c) and C ω5c. The major respiratory quinone was MK-7. The major polar lipid was phosphatidylethanolamine. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain BT18 formed a distinct lineage within the family Hymenobacteraceae (order Cytophagales, class Cytophagia, phylum Bacteroidetes) and was most closely related to members of the genus Hymenobacter, Hymenobacter knuensis 16F7C-2 (97.0% 16S rRNA gene sequence similarity). Optimal growth occurred at 25 °C and pH 7.0 without NaCl. The major fatty acids were iso-C and anteiso-C. The major menaquinone was MK-7. The major polar lipid was phosphatidylethanolamine. Biochemical, chemotaxonomic and phylogenetic analyses indicated that strains BT328 and BT18 represents a novel bacterial species within the genus Spirosoma and Hymenobacter, respectively. For which the name Spirosoma aureum and Hymenobacter russus is proposed. The type strain of S. aureum is BT328 (=KCTC 72365 = NBRC 114506) and the type strain of H. russus is BT18 (=KCTC 62610 = NBRC 114380).
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http://dx.doi.org/10.1007/s10482-020-01492-5DOI Listing
December 2020

Rhodocytophaga rosea sp. nov. and Nibribacter ruber sp. nov., two radiation-resistant bacteria isolated from soil.

Antonie Van Leeuwenhoek 2020 Dec 2;113(12):2177-2185. Epub 2020 Nov 2.

Department of Bio and Environmental Technology, College of Natural Science, Seoul Women's University, Seoul, 01797, Republic of Korea.

Two bacterial strains, 172606-1 and BT10, were isolated from soil, Korea. Both strains were Gram-stain-negative and rod-shaped bacteria. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain 172606-1 formed a distinct lineage within the family Cytophagaceae (order Cytophagales, class Cytophagia, phylum Bacteroidetes). Strain 172606-1 was most closely related to a member of the genus Rhodocytophaga (93.8% 16S rRNA gene sequence similarity to Rhodocytophaga aerolata 5416T-29). The complete genome sequence of strain 172606-1 is 8,983,451 bp size. Optimal growth occurred at 25 °C and pH 7.0 without NaCl. The major cellular fatty acids were identified as iso-C and C ω5c. The major respiratory quinone was MK-7. The major polar lipid was phosphatidylethanolamine. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain BT10 belongs to the genus Nibribacter and is closely related to Nibribacter koreensis GSR 3061 (96.5%), Rufibacter glacialis MDT1-10-3 (95.7%), Rufibacter sediminis H-1 (95.1%) and Rufibacter quisquiliarum CAI-18b (94.9%). The complete genome sequence of strain BT10 is 4,374,810 bp size. The predominant (> 10%) cellular fatty acids of strain BT10 were iso-C and summed feature 4 (anteiso-C B/iso-C I) and a predominant quinone was MK-7. In addition, strain BT10 has phosphatidylethanolamine (PE) as the major polar lipid. On the basis of biochemical, chemotaxonomic and phylogenetic analyses, strain 172606-1 represents a novel bacterial species of the genus Rhodocytophaga, for which the name Rhodocytophaga rosea is proposed and strain BT10 represents a novel species of the genus Nibribacter, for which the name Nibribacter ruber is proposed. The type strains of Rhodocytophaga rosea and Nibribacter ruber are 172606-1 (= KCTC 62096 = NBRC 114410) and BT10 (= KCTC 62607 = NBRC 114383), respectively.
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http://dx.doi.org/10.1007/s10482-020-01488-1DOI Listing
December 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

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

Targeting antioxidant enzymes enhances the therapeutic efficacy of the BCL-X inhibitor ABT-263 in KRAS-mutant colorectal cancers.

Cancer Lett 2021 Jan 15;497:123-136. Epub 2020 Oct 15.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea; Medical Research Center, Genomic Medicine Institute (GMI), Seoul National University College of Medicine, Seoul, 03080, Korea. Electronic address:

Cancer chemotherapeutic drugs exert cytotoxic effects by modulating intracellular reactive oxygen species (ROS) levels. However, whether ROS modulates the efficacy of targeted therapeutics remains poorly understood. Previously, we reported that upregulation of the anti-apoptotic protein, BCL-X, by KRAS activating mutations was a potential target for KRAS-mutant colorectal cancer (CRC) treatment. Here, we demonstrated that the BCL-X targeting agent, ABT-263, increased intracellular ROS levels and targeting antioxidant pathways augmented the therapeutic efficacy of this BH3 mimetic. ABT-263 induced expression of genes associated with ROS response and increased intracellular ROS levels by enhancing mitochondrial superoxide generation. The superoxide dismutase inhibitor, 2-methoxyestradiol (2-ME), exhibited synergism with ABT-263 in KRAS-mutant CRC cell lines. This synergistic effect was attributed to the inhibition of mTOR-dependent translation of the anti-apoptotic MCL-1 protein via caspase 3-mediated cleavage of AKT and S6K. In addition, combination treatment of ABT-263 and 2-ME demonstrated a synergistic effect in in vivo patient-derived xenografts harboring KRAS mutations. Our data suggest a novel role for ROS in BH3 mimetic-based targeted therapy and provide a novel strategy for treatment of CRC patients with KRAS mutations.
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http://dx.doi.org/10.1016/j.canlet.2020.10.018DOI Listing
January 2021