Publications by authors named "Tae Hee Lee"

336 Publications

Association between long-term exposure to particulate matter and childhood cancer: A retrospective cohort study.

Environ Res 2021 Nov 25:112418. Epub 2021 Nov 25.

Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea; Environmental Health Center, The Catholic University of Korea, Seoul, South Korea. Electronic address:

Background: Although particulate matter is a known carcinogen, its association with childhood cancer is inconclusive. The present study aimed to examine the association between long-term exposure to particulate matter and childhood cancer.

Methods: A retrospective cohort was constructed from the claims database of the Korea National Health Insurance Service, including children born in seven metropolitan cities in Korea between 2002 and 2012. Monthly mean concentrations of particulate matter with aerodynamic diameter <10 μm (PM) and other air pollutants (NO, SO, CO, and O) were calculated using data from the AirKorea. Monthly mean concentrations of particulate matter with aerodynamic diameter <2.5 μm (PM) were estimated based on a data fusion approach. Cumulative exposure was assessed by averaging the monthly concentrations accounting for the residential mobility of the children. The occurrence of cancer was identified by the appearance of diagnosis codes in the claims database. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional regression, adjusting for potential confounders and O concentrations.

Results: During the study period, 1725 patients were newly diagnosed with cancer among 1,261,855 children. HR of all cancers per 10 μg/m increment in annual mean concentrations of PM and PM were 3.02 (95% CI: 1.63, 5.59) and 1.04 (0.74, 1.45), respectively.

Conclusion: PM exposure was positively associated with childhood cancer in a large retrospective cohort with exposure assessment accounting for residential mobility.
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http://dx.doi.org/10.1016/j.envres.2021.112418DOI Listing
November 2021

Alertness during working hours among eight-hour rotating-shift nurses: An observational study.

J Nurs Scholarsh 2021 Nov 17. Epub 2021 Nov 17.

Department of Applied Statistics, Yonsei University, Seoul, South Korea.

Purpose: The aim of this study was to identify the patterns of the decline in the alertness of rotating-shift nurses during working hours across different shift types (day, evening, and night) using an objective measure.

Design: An observational study using ReadiBand wrist actigraphs was conducted.

Methods: Data were collected from June 2019 to February 2020. Participants were rotating-shift nurses (N = 82) who provided direct nursing care for patients in acute care hospitals in South Korea. Nurses wore actigraphs continuously for 14 days on their non-dominant hand to identify sleep-wake cycles and predict their alertness scores hourly. All participants completed a sleep diary.

Findings: Nurses working during night shifts had lower average alertness scores (mean = 77.12) than nurses working during day (mean = 79.05) and evening (mean = 91.21). Overall, alertness showed a declining trend and the specific patterns of decline differed across shifts. Participants with alertness scores less than 70 or 80 demonstrated a significant decline in alertness across all shifts.

Conclusions: Distinct patterns of decline in alertness per nursing shift were revealed. Each shift feature should be considered when developing interventions to increase nurses' alertness, promote high-quality care provision, and ensure patient safety.

Clinical Relevance: The implementation of interventions to increase alertness among shift nurses is needed at the organizational level, and the cooperation of nursing managers and administrators is required.
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http://dx.doi.org/10.1111/jnu.12743DOI Listing
November 2021

Medical Management of Constipation in Elderly Patients: Systematic Review.

J Neurogastroenterol Motil 2021 Oct;27(4):495-512

Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Chungcheongnam-do, Korea.

Background/aims: Constipation is a common gastrointestinal problem in the elderly. Because of the limitations of life style modifications and the comorbidity, laxative use is also very common. Therefore, this study reviews the latest literature on the effect and safety of laxative in the elderly.

Methods: A systematic review of randomized controlled trials investigating the effectiveness and safety of laxatives for constipation in elderly patients over 65 years old were performed using the following databases: PubMed, EMBASE, and the Cochrane Library.

Results: Twenty-three randomized controlled trials were included in this review. Among the selected studies, 9 studies compared laxative with placebo and 5 studies compared laxatives of the same type. Four studies compared different types of laxatives or compared combination agents. Five studies compared novel medications such as prucalopride, lubiprostone, and elobixibat with placebo. Psyllium, calcium polycarbophil, lactulose syrup, lactitol, polyethylene glycol, magnesium hydroxide, stimulant laxative with or without fiber, and other medications were more effective than placebo in elderly constipation patients in short-term. Generally, the frequency and severity of adverse effects of laxative were similar between the arms of studies.

Conclusions: Bulk laxative, osmotic laxative, stimulant laxative with or without fiber, and other medications can be used in elderly patients in short-term within 3 months with reasonable safety. However, the quality of included studies was not high and most of studies was conducted in a small number of patients. Among these laxatives, polyethylene glycol seems to be safe and effective in long-term use of about 6 months in elderly patients.
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http://dx.doi.org/10.5056/jnm20210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521458PMC
October 2021

2020 Seoul Consensus on the Diagnosis and Management of Gastroesophageal Reflux Disease.

J Neurogastroenterol Motil 2021 Oct;27(4):453-481

Institute of Medical Sciences, Tzu Chi University, and Department of Public Health, College of Medicine, Tzu Chi University, Hualien City, Taiwan.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.
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http://dx.doi.org/10.5056/jnm21077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521465PMC
October 2021

Fabrication of Formalin-Fixed, Paraffin-Embedded (FFPE) Circulating Tumor Cell (CTC) Block Using a Hydrogel Core-Mediated Method.

Micromachines (Basel) 2021 Sep 20;12(9). Epub 2021 Sep 20.

Department of Internal Medicine, Chungnam National University Hospital, 282, Munwha-ro, Jung-gu, Daejeon 35015, Korea.

Circulating tumor cells (CTCs) are extremely low-frequency cells in the bloodstream. As those cells have detached from the primary tumor tissues and it circulates throughout the whole body, they are considered as promising diagnostic biomarkers for clinical application. However, the analysis of CTC is often restricted due to their rarity and heterogeneity, as well as their short-term presence. Here we proposed formalin-fixed, paraffin-embedded (FFPE) CTC block method, in combination manner with the hydrogel core-mediated CTC accumulation and conventional paraffin tissue block preparation. The hydrogel core specifically captures and releases cancer cells with high efficiency with an immunoaffinity manner. An additional shell structure protects the isolated cancer cells during the FFPE CTC block preparation process. The fabricated FFPE CTC block was sectioned and cytopathologically investigated just the same way as the conventional tissue block. Our results demonstrate that rare cells such as CTCs can also be prepared for FFPE cell blocks and shows great promise for cytopathological CTC studies.
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http://dx.doi.org/10.3390/mi12091128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466852PMC
September 2021

Enzyme aggregation and fragmentation induced by catalysis relevant species.

Phys Chem Chem Phys 2021 Sep 22;23(36):20709-20717. Epub 2021 Sep 22.

Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.

It is usually assumed that enzymes retain their native structure during catalysis. However, the aggregation and fragmentation of proteins can be difficult to detect and sometimes conclusions are drawn based on the assumption that the protein is in its native form. We have examined three model enzymes, alkaline phosphatase (AkP), hexokinase (HK) and glucose oxidase (GOx). We find that these enzymes aggregate or fragment after addition of chemical species directly related to their catalysis. We used several independent techniques to study this behavior. Specifically, we found that glucose oxidase and hexokinase fragment in the presence of D-glucose but not L-glucose, while hexokinase aggregates in the presence of Mg ion and either ATP or ADP at low pH. Alkaline phosphatase aggregates in the presence of Zn ion and inorganic phosphate. The aggregation of hexokinase and alkaline phosphatase does not appear to attenuate their catalytic activity. Our study indicates that specific multimeric structures of native enzymes may not be retained during catalysis and suggests pathways for different enzymes to associate or separate over the course of substrate turnover.
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http://dx.doi.org/10.1039/d1cp02966eDOI Listing
September 2021

Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea.

Pharmaceuticals (Basel) 2021 Aug 9;14(8). Epub 2021 Aug 9.

Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.

This study aims to compare the prevalence and seriousness of adverse events (AEs) among sedatives used in critically ill patients or patients undergoing invasive procedures and to identify factors associated with serious AEs. Retrospective cross-sectional analysis of sedative-related AEs voluntarily reported to the Korea Adverse Event Reporting System from 2008 to 2017 was performed. All AEs were grouped using preferred terms and System Organ Classes per the World Health Organization-Adverse Reaction Terminology. Logistic regression was performed to identify factors associated with serious events. Among 95,188 AEs, including 3132 (3.3%) serious events, the most common etiologic sedative was fentanyl (58.8%), followed by pethidine (25.9%). Gastrointestinal disorders (54.2%) were the most frequent AEs. The most common serious AE was heart rate/rhythm disorders (33.1%). Serious AEs were significantly associated with male sex; pediatrics; etiologic sedative with etomidate at the highest risk, followed by dexmedetomidine, ketamine, and propofol; polypharmacy; combined sedative use; and concurrent use of corticosteroids, aspirin, neuromuscular blockers, and antihistamines (reporting odds ratio > 1, < 0.001 for all). Sedative-induced AEs are most frequently reported with fentanyl, primarily manifesting as gastrointestinal disorders. Etomidate is associated with the highest risk of serious AEs, with the most common serious events being heart rate/rhythm disorders.
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http://dx.doi.org/10.3390/ph14080783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399659PMC
August 2021

Endoscopy within 7 days after detecting high calprotectin levels can be useful for therapeutic decision-making in ulcerative colitis.

Medicine (Baltimore) 2021 Aug;100(34):e27065

Department of biostatistics, Soonchunhyang University College of Medicine, Seoul, Korea.

Abstract: The aim of this study was to assess the appropriate time interval to identify the association between the fecal calprotectin (FC) test and endoscopic activity, and to evaluate whether the time interval affects the therapeutic plan adjustment in patients with ulcerative colitis (UC).This study included 103 patients who underwent FC tests and endoscopic examinations within the past three months. The FC test results classified cases into three groups as follows: moderate to severe (>200, >250, or >300 μg/g), mild (100-200, 100-250, or 100-300 μg/g), and inactive (<100 μg/g) activity. The Mayo endoscopic subscore was used to determine endoscopic activity. Therapeutic plan adjustment included the addition or increased dosage of anti-inflammatory drugs, steroids, immunomodulators, and biologics.Using the cutoff value for FC of 200 μg/g, the appropriate time interval for dividing the association and non-association between Mayo endoscopic subscore and FC was 7 days (sensitivity, 74.4%; specificity, 50.0%; area under the curve [AUC], 0.6032). When using FC 250 or 300 μg/g, the appropriate time interval was 5.5 days, with a sensitivity of 71.7% and specificity of 49.1 (AUC 0.5862) in FC 250 μg/g, a sensitivity of 69.6%, and a specificity of 47.4 (AUC 0.5549) for FC 300 μg/g. Therapeutic plans changed in 29.1% of patients. In patients with shorter intervals (≤7 days) between the FC test and endoscopy, significant therapeutic plan adjustments were observed in patients with UC (36.5% vs. 17.5%, P = .047).Although the need for endoscopy within 7 days after detecting high FC (≥ 200 μg/g) was not statistically supported, endoscopy within a shorter interval (≤7 days) in UC patients with high FC can help determine the therapeutic plan.
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http://dx.doi.org/10.1097/MD.0000000000027065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389889PMC
August 2021

Calculation of Cement Composition Using a New Model Compared to the Bogue Model.

Materials (Basel) 2021 Aug 19;14(16). Epub 2021 Aug 19.

School of Civil and Environmental Engineering, Yonsei University, Seoul 03722, Korea.

The major cement composition ratios of alite, belite, aluminate, and ferrite have been calculated with the Bogue models until now. However, a recent comprehensive analysis based on various experimental data has revealed that the chemical composition of alite, belite, aluminate, and ferrite implemented by the Bogue models are slightly different than the experimental data, where small amounts of AlO and FeO existing in alite and belite can change the prediction of cement composition. Since the amounts of cement compound are very important factors in determining the properties of concrete, improvement in the calculation would give more precise prediction for application usages such as climate change adaptable cement and high durable concrete manufacturing. For this purpose, 20 new models are proposed by modifying chemical compositions of the cement compounds and verified with the 50 experimental data sets. From the verification, the most accurate models are identified. The calculation using new models exhibit an accuracy improvement of approximately 5% compared to the Bogue models. Their applicable range is also presented. The study results are discussed in detail in the paper.
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http://dx.doi.org/10.3390/ma14164663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401079PMC
August 2021

The Specific Gravity-Free Method for the Isolation of Circulating Tumor KRAS Mutant DNA and Exosome in Colorectal Cancer.

Micromachines (Basel) 2021 Aug 20;12(8). Epub 2021 Aug 20.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Hospital, 282, Munwha-ro, Jung-gu, Daejeon 35015, Korea.

Background: Circulating tumor DNA (ctDNA) and exosome have been widely researched in the field of medical technology and diagnosis platforms. The purpose of our study was to improve the capturing properties of ctDNA and exosome, which involved combining two beads using approaches that may provide a new method for cancer diagnoses.

Methods: We present a dual isolation system including a polydopamine (PDA)-silica-coated alginate bead for circulating tumor DNA (ctDNA) capture and an anti-CD63 immobilized bead for exosome capture. We examined the ctDNA mutation in pre-operative plasma samples obtained from 91 colorectal cancer (CRC) patients using a droplet digital PCR (ddPCR).

Results: The area under the curve (AUROC) of ctKRAS G12D mutation in the buffy coat was 0.718 (95% CI: 0.598-0.838; = 0.001). Patients with CRC that had unmethylation of MLH1 and MSH2 showed significantly higher buffy coat ctKRAS G12D mutations, ascites ctKRAS G12D mutations, miR-31-5, and mixed scores than the patients with a methylation of MLH1 and MSH2.

Conclusion: Our proposed alginate bead using the specific gravity-free method suggests that the screening of mutated ctKRAS DNA and miR-31-5 by liquid biopsy aids in identifying the patients, predicting a primary tumor, and monitoring in the early detection of a tumor.
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http://dx.doi.org/10.3390/mi12080987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400105PMC
August 2021

A Nationwide Survey on the Facilities and Personnel for Endoscopic Sedation: Results from 50 Qualified Endoscopy Units of Teaching Hospitals Accredited by the Korean Society of Gastrointestinal Endoscopy (KSGE).

Clin Endosc 2021 Jul 14. Epub 2021 Jul 14.

Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Background/aims: This study aimed to determine the current status of facilities, equipment, and personnel for endoscopic sedation from endoscopy units of representative hospitals in South Korea.

Methods: A questionnaire survey was conducted on 50 qualified endoscopy units accredited by the Korean Society of Gastrointestinal Endoscopy.

Results: All included endoscopy units had regulations and educational programs regarding sedation training for endoscopists and nursing personnel. There present one assisting nurse during endoscopy in 35 units (70%) and at least two nurses in 12 units (24.0%). All endoscopy units had examination rooms equipped with oxygen supply and suction systems. Endoscopist-directed sedation was performed in 48 units (96.0%). Propofol-based sedation was the most used sedation method. All units had a separate recovery bay. The daily number of patients per bed was greater than 10 in 17 units (34.0%). In 26 (52.0%) units, a single nurse cared for ≥10 patients per day. All the units fulfilled the discharge criteria.

Conclusions: This study presents data regarding endoscopic sedation clinical practice in 50 endoscopy units in South Korea. This study presents the current status of endoscopic sedation clinical practice in 50 qualified endoscopy units accredited by the KSGE, which provide excellent quality management.
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http://dx.doi.org/10.5946/ce.2021.014DOI Listing
July 2021

Endoscopic and Percutaneous Biliary Interventions after Liver Transplantation: Nationwide Data in Korea.

Gut Liver 2021 Jul 12. Epub 2021 Jul 12.

Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.

Background/aims: Biliary complications including biliary strictures and bile leaks are the most common complications that occur after liver transplantation (LT). Endoscopic treatment with endoscopic retrograde cholangiography (ERC) is considered the first-line treatment, and percutaneous transhepatic cholangiography (PTC) can serve as an alternative or rescue therapy. However, nationwide clinical data on the frequency of ERC and PTC following LT have not yet been investigated.

Methods: Using the nationwide claims database, we investigated patients who underwent LT between 2012 and 2014 in Korea and followed them until 2015. We analyzed the prevalence and characteristics of patients and biliary procedures, including ERC and PTC implemented after LT.

Results: A total of 3,481 patients underwent LT during the 3-year study period. Among them, 3.0% of patients underwent biliary intervention postoperatively during the same hospitalization period, and 21.4% of patients received biliary intervention later on after initially being discharged from the hospital following LT. A total of 16.9% and 12.1% of patients underwent ERC and PTC after LT, respectively. The median period from LT to the first biliary intervention was 7.8 months (interquartile range, 3.5 to 14.6 months), and these patients underwent an average of 3.2±2.8 biliary procedures during the follow-up period. Patients undergoing living donor LT were more than twice as likely to undergo biliary procedures as those undergoing deceased donor LT (25.5% vs 12.1%).

Conclusions: Approximately one-fourth of patients in Korea who underwent LT subsequently underwent ERC or PTC. Compared with deceased donor LT patients, those undergoing living donor LT underwent more biliary interventions and were more difficult to treat.
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http://dx.doi.org/10.5009/gnl20379DOI Listing
July 2021

KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease.

Clin Mol Hepatol 2021 Jul 22;27(3):363-401. Epub 2021 Jun 22.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3350/cmh.2021.0178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273632PMC
July 2021

Conformational Dynamics of Poly(T) Single-Stranded DNA at the Single-Molecule Level.

J Phys Chem Lett 2021 May 10;12(19):4576-4584. Epub 2021 May 10.

Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

The conformational dynamics of single-stranded DNA (ss-DNA) are implicated in the mechanisms of several key biological processes such as DNA replication and damage repair and have been modeled with those of semiflexible or flexible polymer. The high flexibility and customizability of ss-DNA also make it an excellent polymeric material for materials engineering. Polythymidine (poly(T)) is an excellent model ss-DNA as a flexible polymer since it does not form any secondary structure. However, only limited experimental results have been reported of poly(T) conformational dynamics with a very short length that is not relevant to the aforementioned processes and applications. Here, we provide the first experimental results of the conformational dynamics of poly(T) with lengths in the range of 130-170 nucleotides at the single-molecule level. Our experiments are based on single-molecule FRET and a DNA hairpin structure of which the folding kinetics are governed by the conformational dynamics of poly(T). We found that the folding kinetics deviate far from those of a flexible polymer model with a harmonic bending potential. To this end, we derived a simple model for the kinetics of DNA hairpin folding from the self-avoiding-walk (SAW). Our model describes the conformational dynamics of poly(T) very well and enables estimation of the conformational dimensionality. The estimated dimensionalities suggest that ss-DNA is completely flexible at 100 mM or a higher NaCl concentration, but not at 50 mM. These results will help understand the conformational dynamics of ss-DNA implicated in several key biological processes and maximize the utility of ss-DNA for materials engineering. Also, our system and model provide an excellent platform to investigate the conformational dynamics of ss-DNA.
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http://dx.doi.org/10.1021/acs.jpclett.1c00962DOI Listing
May 2021

Clinical Outcomes between P1 and P0 Lesions for Obscure Gastrointestinal Bleeding with Negative Computed Tomography and Capsule Endoscopy.

Diagnostics (Basel) 2021 Apr 6;11(4). Epub 2021 Apr 6.

Department of biostatistics, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yongsan-Gu, Seoul 04401, Korea.

Background: A simple classification for the relevance of lesions (P0, P1, and P2; no bleeding potential, less likely to bleed, and more likely to bleed, respectively) based on capsule endoscopy (CE) findings has been used. This study aimed at investigating rebleeding rates and predictive factors of P0 and P1 lesions after obtaining negative findings in both, CE and computed tomography (CT), for patients with obscure gastrointestinal bleeding (OGIB).

Methods: Among 193 patients resulted in negative CE findings defined as P0 or P1 lesions, 84 patients with negative results on CT images were enrolled in this study. The rebleeding rates and predictive factors were assessed in the P0 and P1 groups.

Results: Overall rebleeding rate in patients with negative CT and CE was 17.9%; 18.4% in the P0 group; 17.4% in the P1 group within a median follow-up duration of 18.5 months. In the P0 and P1 groups, the cumulative rebleeding rates were 9.2%, 25.4%, and 25.4%, and 6.9%, 11.8%, and 18.6% at 12, 24, and 60 months, respectively ( = 0.97). There were no independent rebleeding associated factors in the P0 group, whereas Charlson comorbidity index (CCI) (hazard ratio (HR) = 2.019, 95% confidence interval (CI): 1.158-3.519, = 0.013), and initial low hemoglobin (Hb) level (<8 g/dL) (HR = 15.085, 95% CI: 1.182-192.514, = 0.037) were independent predictive factors responsible for rebleeding in the P1 group.

Conclusions: Despite having negative findings on CT and CE, patients with OGIB have a significant potential rebleeding risk. Although there was no significant difference in rebleeding rates between the P0 and P1 groups on CE, the P1 group, with CCI or low initial Hb level, should be cautiously observed after the first bleeding episode.
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http://dx.doi.org/10.3390/diagnostics11040657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067371PMC
April 2021

There Is Something More Important Than Proximal Reflux Episode in the Development of Post-reflux Swallow-induced Peristaltic Wave.

Authors:
Tae Hee Lee

J Neurogastroenterol Motil 2021 Apr;27(2):305-306

Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University Seoul Hospital, Seoul, Korea.

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http://dx.doi.org/10.5056/jnm20276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026371PMC
April 2021

FRET-based dynamic structural biology: Challenges, perspectives and an appeal for open-science practices.

Elife 2021 03 29;10. Epub 2021 Mar 29.

Departments of Biology and Chemistry, Johannes Gutenberg University, Mainz, Germany.

Single-molecule FRET (smFRET) has become a mainstream technique for studying biomolecular structural dynamics. The rapid and wide adoption of smFRET experiments by an ever-increasing number of groups has generated significant progress in sample preparation, measurement procedures, data analysis, algorithms and documentation. Several labs that employ smFRET approaches have joined forces to inform the smFRET community about streamlining how to perform experiments and analyze results for obtaining quantitative information on biomolecular structure and dynamics. The recent efforts include blind tests to assess the accuracy and the precision of smFRET experiments among different labs using various procedures. These multi-lab studies have led to the development of smFRET procedures and documentation, which are important when submitting entries into the archiving system for integrative structure models, PDB-Dev. This position paper describes the current 'state of the art' from different perspectives, points to unresolved methodological issues for quantitative structural studies, provides a set of 'soft recommendations' about which an emerging consensus exists, and lists openly available resources for newcomers and seasoned practitioners. To make further progress, we strongly encourage 'open science' practices.
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http://dx.doi.org/10.7554/eLife.60416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007216PMC
March 2021

Palliative endoscopic retrograde biliary drainage for malignant biliary obstruction in Korea: A nationwide assessment.

Saudi J Gastroenterol 2021 May-Jun;27(3):173-177

Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.

Background: Malignant biliary obstruction (MBO) is usually caused by biliary tract cancer or pancreatic cancer. This study was performed to summarize the current situation regarding palliative endoscopic retrograde biliary drainage (ERBD) for MBO in Korea and to determine its clinical significance by analyzing representative nationwide data.

Methods: Patients that underwent palliative ERBD for MBO between 2012 and 2015 were identified using the Health Insurance Review and Assessment database, which covers the entire Korean population. We assessed clinical characteristics and complications and compared the clinical impacts of initial metal and plastic stenting in these patients.

Results: A total of 9,728 subjects (mean age, 65 ± 11.4 years; male, 61.4%) were identified and analyzed. The most common diagnosis was malignant neoplasm of liver and intrahepatic bile ducts (32.1%) and this was followed by extrahepatic or Ampulla of Vater cancer and pancreatic cancer. Initial plastic stent(s) placement was performed in 52.9% of the study subjects, and metal stent(s) placement was performed in 23.3%. The number of sessions of endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) was significantly higher in patients that underwent initial plastic stenting than in patients that underwent metal stenting (2.2 ± 1.7 vs 1.8 ± 1.4, P < 0.0001), but rates of post-ERCP pancreatitis, hospital days, and time to second ERCP or PTBD were not significantly different.

Conclusion: This nationwide assessment study suggests that initial metal stenting is associated with fewer sessions of total ERCP or PTBD following the initial procedure, despite the preference for initial plastic stenting in Korea.
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http://dx.doi.org/10.4103/sjg.sjg_589_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265398PMC
August 2021

Reliability and validity of the Korean version of the University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract instrument in patients with systemic sclerosis.

Korean J Intern Med 2021 Nov 10;36(6):1504-1514. Epub 2021 Feb 10.

Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea.

Background/aims: Systemic sclerosis (SSc) is associated with a wide range of gastrointestinal (GI) changes. The University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) instrument is a self-administered GI assessment instrument for patients with SSc. We developed a Korean version of the UCLA SCTC GIT 2.0 instrument and evaluated its reliability and internal consistency.

Methods: The participants were 37 Korean patients with SSc. Translation and cross-cultural adaptation of the UCLA SCTC GIT 2.0 were performed according to international standardized guidelines. We evaluated reproducibility by calculating the intraclass correlation coefficients and assessed the internal consistency of the Korean version of the UCLA SCTC GIT 2.0. We assessed its construct validity by evaluating its correlations with the Short Form Health Survey version 2 and EQ-5D scores by means of Spearman correlation analyses.

Results: Patients with SSc were mostly women (89.19%) with a mean age of 52.2 years, median disease duration of 24 months, and median modified Rodnan total skin score of 4. The median total GIT score on the UCLA SCTC GIT 2.0 was 0.3. The UCLA SCTC GIT 2.0 Korean version showed excellent internal consistency (Cronbach's α of total GIT score = 0.863). Most domains of the ULCA SCTC GIT 2.0 were correlated with those of the EuroQol (EQ)-5D score.

Conclusion: The Korean version of the UCLA SCTC GIT 2.0 has acceptable internal consistency, reliability, and validity. Therefore, it can be used to assess GIT involvement in Korean patients with SSc.
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http://dx.doi.org/10.3904/kjim.2020.190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588985PMC
November 2021

Characteristics of symptomatic belching in patients with belching disorder and patients who exhibit gastroesophageal reflux disease with belching.

J Neurogastroenterol Motil 2021 Apr;27(2):231-239

Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea.

Background/aims: Belching disorder (BD) is clinically distinct from gastroesophageal reflux disease (GERD) with belching. Supragastric belching (SGB) is closely associated with reflux episodes. This study investigates belch characteristics in association with reflux, compared between patients with BD and those who had GERD with belching.

Methods: Impedance pH monitoring data from 10 patients with BD and 10 patients with GERD who exhibited belching were retrospectively analyzed. Belches were considered "isolated" or "reflux-related" and acidic/non-acidic. Belch characteristics were compared between patients with BD and those with GERD.

Results: Symptomatic belches were more frequent in patients with BD than in patients with GERD (median, 160.5 vs 56.0, < 0.05). SGB was the most common type in both groups; common subtypes comprised "isolated" in patients with BD and "isolated during the reflux period" in patients with GERD. Reflux-related SGB was more common in patients with GERD than in BD (78.3% vs 45.2%, < 0.005). Both "preceding belching" including the reflux period and acidic SGB were more common in patients with GERD than in BD (31.8% vs 8.6% and 38.1% vs 8.9%, both < 0.05). Supragastric belch number positively correlated with all reflux episodes in patients with GERD (adjusted = 0.572, = 0.007).

Conclusions: BD is characterized by more belching, compared to GERD. SGB is more frequently associated with reflux in GERD than in BD; acidity may be related to GERD. In BD, SGB is typically non-acidic and unrelated to reflux. Distinct SGB characteristics may reflect different pathogenic mechanisms of reflux and associated symptoms.
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http://dx.doi.org/10.5056/jnm20114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026376PMC
April 2021

Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer.

PLoS One 2020 2;15(12):e0242145. Epub 2020 Dec 2.

Department of Senior Healthcare, BK21 plus program, Graduated School, Eulji University, Daejeon, Republic of Korea.

Although circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of various tumors, clinical correlation of cfDNA with gastric cancer has not been fully understood. To address this, we developed a highly sensitive cfDNA capture system by integrating polydopamine (PDA) and silica. PDA-silica hybrids incorporated different molecular interactions to a single system, enhancing cfDNA capture by 1.34-fold compared to the conventional silica-based approach (p = 0.001), which was confirmed using cell culture supernatants. A clinical study using human plasma samples revealed that the diagnostic accuracy of the new system to be superior than the commercially available cfDNA kit, as well as other serum antigen tests. Among the cancer patients, plasma cfDNA levels exhibited a good correlation with the size of a tumor. cfDNA was also predicative of distant metastasis, as the median cfDNA levels of metastatic cancer patients were ~60-fold higher than those without metastasis (p = 0.008). Furthermore, high concordance between tissue biopsy and cfDNA genomic analysis was found, as HER2 expression in cfDNA demonstrated an area under ROC curve (AUC) of 0.976 (p <0.001) for detecting patients with HER2-positive tumors. The new system also revealed high prognostic capability of cfDNA, as the concentration of cfDNA was highly associated with the survival outcomes. Our novel technology demonstrates the potential to achieve efficient detection of cfDNA that may serve as a reliable biomarker for gastric tumor.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242145PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710035PMC
January 2021

Nucleosome Dynamics during Transcription Elongation.

ACS Chem Biol 2020 12 2;15(12):3133-3142. Epub 2020 Dec 2.

The nucleosome is the basic packing unit of the eukaryotic genome. Dynamic interactions between DNA and histones in the nucleosome are the molecular basis of gene accessibility regulation that governs the kinetics of various DNA-templated processes such as transcription elongation by RNA Polymerase II (Pol II). On the basis of single-molecule FRET measurements with chemically modified histones, we investigated the nucleosome dynamics during transcription elongation and how it is affected by histone acetylation at H3 K56 and the histone chaperone Nap1, both of which can affect DNA-histone interactions. We observed that H3K56 acetylation dramatically shortens the pause duration of Pol II near the entry region of the nucleosome, while Nap1 induces no noticeable difference. We also found that the elongation rate of Pol II through the nucleosome is unaffected by the acetylation or Nap1. These results indicate that H3K56 acetylation facilitates Pol II translocation through the nucleosome by assisting paused Pol II to resume and that Nap1 does not affect Pol II progression. Following transcription, only a small fraction of nucleosomes remain intact, which is unaffected by H3K56 acetylation or Nap1. These results suggest that (i) spontaneous nucleosome opening enables Pol II progression, (ii) Pol II mediates nucleosome reassembly very inefficiently, and (iii) Nap1 in the absence of other factors does not promote nucleosome disassembly or reassembly during transcription.
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http://dx.doi.org/10.1021/acschembio.0c00617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749077PMC
December 2020

PCNA Monoubiquitination Is Regulated by Diffusion of Rad6/Rad18 Complexes along RPA Filaments.

Biochemistry 2020 12 27;59(49):4694-4702. Epub 2020 Nov 27.

Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

Translesion DNA synthesis (TLS) enables DNA replication through damaging modifications to template DNA and requires monoubiquitination of the proliferating cell nuclear antigen (PCNA) sliding clamp by the Rad6/Rad18 complex. This posttranslational modification is critical to cell survival following exposure to DNA-damaging agents and is tightly regulated to restrict TLS to damaged DNA. Replication protein A (RPA), the major single-strand DNA (ssDNA) binding protein complex, forms filaments on ssDNA exposed at TLS sites and plays critical yet undefined roles in regulating PCNA monoubiquitination. Here, we utilize kinetic assays and single-molecule FRET microscopy to monitor PCNA monoubiquitination and Rad6/Rad18 complex dynamics on RPA filaments, respectively. Results reveal that a Rad6/Rad18 complex is recruited to an RPA filament via Rad18·RPA interactions and randomly translocates along the filament. These translocations promote productive interactions between the Rad6/Rad18 complex and the resident PCNA, significantly enhancing monoubiquitination. These results illuminate critical roles of RPA in the specificity and efficiency of PCNA monoubiquitination and represent, to the best of our knowledge, the first example of ATP-independent translocation of a protein complex along a protein filament.
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http://dx.doi.org/10.1021/acs.biochem.0c00849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887432PMC
December 2020

Transient Anal Sphincter Relaxations Are a Normal Phenomenon in Healthy Subjects: Author's Reply.

Authors:
Tae Hee Lee

J Neurogastroenterol Motil 2020 09;26(4):554-555

Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University Seoul Hospital, Seoul, Korea.

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http://dx.doi.org/10.5056/jnm20195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547193PMC
September 2020

Esophageal Involvement and Determinants of Perception of Esophageal Symptoms Among South Koreans With Systemic Sclerosis.

J Neurogastroenterol Motil 2020 09;26(4):477-485

Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea.

Background/aims: Our study aims to characterize esophageal motor function; evaluate the relationships among esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM), and 24-hour esophageal multichannel intraluminal impedance monitoring combined with pH-metry (MII-pH); and elucidate the determinants of esophageal symptom perception in South Koreans with systemic sclerosis (SSc).

Methods: We reviewed prospectively collected HRM (n = 46), EGD (n = 41), and MII-pH (n = 37) data from 46 consecutive patients with SSc (42 females; mean age 50.1 years) who underwent esophageal tests between June 2013 and September 2018.

Results: The most common HRM diagnosis was normal (39.1%), followed by ineffective esophageal motility (23.9%) and absent contractility (21.7%). Erosive esophagitis was observed in 12.2% of total SSc patients, with a higher frequency in patients with absent contractility than those with normal motility (44.5% vs 0.0%, = 0.01). Pathologic acid exposure was observed in 6 patients (20.0%) and positive symptom association in 18 patients (60.0%) in MII-pH tests of symptomatic patients. The proportion of SSc patients with esophageal symptoms not explained by reflux or mucosal or motor esophageal abnormalities was 33.0%.

Conclusions: Esophageal involvement among South Koreans with SSc was characterized by heterogeneous motility patterns, with a higher prevalence of normal motility and lower prevalence of erosive esophagitis. Reflux hypersensitivity or functional heartburn might be partly attributed to the perception of esophageal symptoms in SSc patients who have neither gastroesophageal reflux disease nor esophageal dysmotility.
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http://dx.doi.org/10.5056/jnm19148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547196PMC
September 2020

Self-Healable Reprocessable Triboelectric Nanogenerators Fabricated with Vitrimeric Poly(hindered Urea) Networks.

ACS Nano 2020 Sep 1;14(9):11442-11451. Epub 2020 Sep 1.

Department of Chemistry and Biochemistry, Concordia University, Montreal, Quebec Canada H4B 1R6.

In recent years, the advent of highly deformable and healable electronics is exciting and promising for next-generation electronic devices. In particular, self-healable triboelectric nanogenerators (SH-TENGs) serve as promising candidates based on the combination of the triboelectric effect, electrostatic induction, and self-healing action. However, the majority of SH-TENGs have been devised with weak polymeric networks that are healed with reversible supramolecular interactions or disulfides, thus resulting in poor mechanical properties and low resistance to creeping. To address this issue, we demonstrate the integration of mechanically strong and self-healable poly(hindered urea) (PHU) network in the fabrication of effective TENGs. The designed PHU network is flexible but shows greater mechanical property of tensile strength as high as 1.7 MPa at break. The network is capable of self-healing quickly and repeatedly as well as being reprocessable under mild conditions, enabling the recovery of triboelectric performances after the complete healing of the damaged surfaces. Furthermore, the interfacial-polarization-induced enhancement of dielectric constant endows our SH-TENG with the highest triboelectric output performance (169.9 V/cm) among the reported healable TENGs. This work presents an avenue to the development of mechanical energy-harvesting devices and self-powered sensors with excellent stretchability, high recoverability, and good mechanical strength.
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http://dx.doi.org/10.1021/acsnano.0c03819DOI Listing
September 2020

A MARTX Toxin Gene Is Controlled by Host Environmental Signals through a CRP-Coordinated Regulatory Network in Vibrio vulnificus.

mBio 2020 07 28;11(4). Epub 2020 Jul 28.

National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

A multifunctional autoprocessing repeats-in-toxin (MARTX) toxin plays an essential role in the virulence of many pathogens, including a fulminating human pathogen H-NS and HlyU repress and derepress expression of the MARTX toxin gene in , respectively. However, little is known about other regulatory proteins and environmental signals involved in regulation. In this study, we found that a leucine-responsive regulatory protein (Lrp) activates by binding directly and specifically to the promoter, P Phased hypersensitivity resulting from DNase I cleavage of the P regulatory region suggests that Lrp probably induces DNA bending in P Lrp activates P independently of H-NS and HlyU, and leucine inhibits Lrp binding to P and reduces the Lrp-mediated activation. Furthermore, a cyclic AMP receptor protein (CRP) represses P , and exogenous glucose relieves the CRP-mediated repression. Biochemical and mutational analyses demonstrated that CRP binds directly and specifically to the upstream region of P , which presumably alters the DNA conformation in P and thus represses Moreover, CRP represses expression of and by binding directly to their upstream regions, forming coherent feed-forward loops with Lrp and HlyU. In conclusion, expression of is controlled by a regulatory network comprising CRP, Lrp, H-NS, and HlyU in response to changes in host environmental signals such as leucine and glucose. This collaborative regulation enables the elaborate expression of , thereby enhancing the fitness and pathogenesis of during the course of infection. A MARTX toxin, RtxA, is an essential virulence factor of many pathogens, including species. H-NS and HlyU repress and derepress, respectively, expression of a life-threatening pathogen, We found that Lrp directly activates independently of H-NS and HlyU, and leucine inhibits the Lrp-mediated activation of Furthermore, we demonstrated that CRP represses but derepresses in the presence of exogenous glucose. CRP represses not only directly by binding to upstream of but also indirectly by repressing and This is the first report of a regulatory network comprising CRP, Lrp, H-NS, and HlyU, which coordinates the expression in response to environmental signals such as leucine and glucose during infection. This elaborate regulatory network will enhance the fitness of and contribute to its successful infection within the host.
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http://dx.doi.org/10.1128/mBio.00723-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387792PMC
July 2020

Identification of a Clinical Cutoff Value for Multiplex KRAS Mutation Detection in Colorectal Adenocarcinoma Patients Using Digital Droplet PCR, and Comparison with Sanger Sequencing and PNA Clamping Assay.

J Clin Med 2020 Jul 18;9(7). Epub 2020 Jul 18.

Department of Pathology, Chungnam National University School of Medicine, Daejeon 266, Korea.

KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) is a major predictive marker for anti-epidermal growth factor receptor treatment, and determination of KRAS mutational status is crucial for successful management of colorectal adenocarcinoma. More standardized and accurate methods for testing KRAS mutation, which is vital for therapeutic decision-making, are required. Digital droplet polymerase chain reaction (ddPCR) is an advanced digital PCR technology developed to provide absolute quantitation of target DNA. In this study, we validated the clinical performance of ddPCR in determination of KRAS mutational status, and compared ddPCR results with those obtained by Sanger sequencing and peptide nucleic acid-clamping. Of 81 colorectal adenocarcinoma tissue samples, three repeated sets of KRAS mutation were measured by ddPCR, yielding high consistency (ICC = 0.956). Receiver operating characteristic (ROC) curves were constructed to determine KRAS mutational status based on mutant allele frequency generated by ddPCR. Using the best threshold cutoff (mutant allele frequency of 7.9%), ddPCR had superior diagnostic sensitivity (100%) and specificity (100%) relative to the two other techniques. Thus, ddPCR is effective for detecting the KRAS mutation in colorectal adenocarcinoma tissue samples. By allowing definition of the optimal cutoff, ddPCR represents a potentially useful diagnostic tool that could improve diagnostic sensitivity and specificity.
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http://dx.doi.org/10.3390/jcm9072283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409004PMC
July 2020

Can We Apply the Salivary Pepsin Test for Patients With Gastroesophageal Reflux Disease in Primary Practice?

Authors:
Tae Hee Lee

J Neurogastroenterol Motil 2020 07;26(3):417-418

Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University Seoul Hospital, Seoul, Korea.

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http://dx.doi.org/10.5056/jnm20047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329161PMC
July 2020
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