Publications by authors named "Jin Hyung Lee"

160 Publications

Recent findings and future directions of grafted gum karaya polysaccharides and their various applications: A review.

Carbohydr Polym 2021 Apr 23;258:117687. Epub 2021 Jan 23.

Schoolof Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea. Electronic address:

Gum karaya is a polysaccharide that has several industrial applications in the pharmaceutical, food, and environmental fields owing to its hydrophilic, anionic, and biocompatible nature. Gum karaya and its modified forms have been assessed for drug delivery, wastewater treatment, and food industry applications. This review provides a comprehensive overview of various synthetic methods of modification of gum karaya, such as grafting initiated through free radical, microwave-assisted grafting, radiation-assisted, and enzyme-assisted modification methods. In addition, the review outlines collective industrial applications of modified gum karaya in drug delivery systems, removal of heavy atoms, dyes, food, and other biological activities, and suggests possible prospects for gum karaya modification and their remarkable industrial applications.
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http://dx.doi.org/10.1016/j.carbpol.2021.117687DOI Listing
April 2021

Evaluating enzyme stabilizations in calcium carbonate: Comparing in situ and crosslinking mediated immobilization.

Int J Biol Macromol 2021 Apr 5;175:341-350. Epub 2021 Feb 5.

Department of Food Biotechnology, Dong-A University, Busan 49315, Republic of Korea. Electronic address:

Enzyme immobilization using inorganic materials has been shown to preserve enzyme activity improving and improve their practical applications in biocatalytic process designs. Proper immobilization methods have been used to obtain high recycling and storage stability. In this study, we compared the activity and stability of in situ or crosslink-immobilized enzymes in a CaCO biomineral carrier. More than 30% of the initial enzyme activity was preserved for both the systems after 180 days upon 15 activity measurements at room temperature, confirming the improved stability of these enzyme systems (100 mM phosphate buffer, pH 8.0); however, differences in enzyme loading, activity, and characteristics were observed for each of these methods. Each system exhibited efficacy of 80% and 20%, respectively. Based on the same amount of immobilized enzyme (0.2 mg), the specific activities of hydrolysis of p-nitrophenyl butyrate substrate at room temperature of in situ immobilized carboxyl esterase (CE) and crosslinked CE were 11.37 and 7.63 mM min mg, respectively (100 mM phosphate buffer, pH 8.0). Moreover, based on the kinetic behavior, in situ immobilized CE exhibited improved catalytic efficiency (Vmax Km) of the enzyme, exhibiting 4-fold higher activity and efficiency values than those of the CE immobilized in CaCO. This is the first study to describe the stabilization of enzymes in CaCO and compare the enzyme kinetics and efficiencies between in situ immobilization and crosslinking in CaCO carriers.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.028DOI Listing
April 2021

α-Tocopherol-loaded reactive oxygen species-scavenging ferrocene nanocapsules with high antioxidant efficacy for wound healing.

Int J Pharm 2021 Mar 22;596:120205. Epub 2021 Jan 22.

Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea. Electronic address:

The elevated production of reactive oxygen species (ROS) in wounded sites triggers a series of harmful effects, including cellular senescence, fibrotic scar formation, and inflammation. Therefore, alleviating oxidative stress in the microenvironment of wounded sites might promote regenerative wound healing. Generally, ROS-scavenging nanocapsules are effective for treating wounds owing to their anti-oxidative stress activity and targeted effects. In this study, a highly versatile ferrocene functional polymer was synthesized by one-pot radical polymerization, for formulating self-assembled ferrocene nanocapsules (FNCs), which could function as smart carriers of an antioxidant, α-tocopherol (TP), with high stability and loading efficiency. The FNCs showed ROS-sensitive properties, as demonstrated using dynamic light scattering, transmission electron microscopy, and the controlled release of a model drug in an ROS microenvironment. The antioxidant activity of TP-loaded FNCs, analyzed using 2,2-diphenyl-1-picrylhydrazyl assay, was significantly higher than that of unloaded TP. Furthermore, TP-loaded FNCs repressed oxidative damage to mouse NIH 3T3 fibroblasts and reduced intracellular ROS production according to an in vitro antioxidant assay. Most importantly, TP-loaded FNCs showed good biocompatibility and greatly facilitated the healing of infected wounds, as demonstrated using a scratch assay. Therefore, TP-loaded FNCs have potential as an ROS-mediated drug delivery system to treat various oxidative stress-associated diseases.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120205DOI Listing
March 2021

Antibiofilm and antifungal activities of medium-chain fatty acids against Candida albicans via mimicking of the quorum-sensing molecule farnesol.

Microb Biotechnol 2020 Nov 30. Epub 2020 Nov 30.

School of Chemical Engineering, Yeungnam University, Gyeongsan, Korea.

Candida biofilms are tolerant to conventional antifungal therapeutics and the host immune system. The transition of yeast cells to hyphae is considered a key step in C. albicans biofilm development, and this transition is inhibited by the quorum-sensing molecule farnesol. We hypothesized that fatty acids mimicking farnesol might influence hyphal and biofilm formation by C. albicans. Among 31 saturated and unsaturated fatty acids, six medium-chain saturated fatty acids, that is, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid and lauric acid, effectively inhibited C. albicans biofilm formation by more than 75% at 2 µg ml with MICs in the range 100-200 µg ml . These six fatty acids at 2 µg ml and farnesol at 100 µg ml inhibited hyphal growth and cell aggregation. The addition of fatty acids to C. albicans cultures decreased the productions of farnesol and sterols. Furthermore, down-regulation of several hyphal and biofilm-related genes caused by heptanoic or nonanoic acid closely resembled the changes caused by farnesol. In addition, nonanoic acid, the most effective compound diminished C. albicans virulence in a Caenorhabditis elegans model. Our results suggest that medium-chain fatty acids inhibit more effectively hyphal growth and biofilm formation than farnesol.
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http://dx.doi.org/10.1111/1751-7915.13710DOI Listing
November 2020

Antibiofilm and Antivirulence Properties of Indoles Against .

Front Microbiol 2020 30;11:584812. Epub 2020 Oct 30.

School of Chemical Engineering, Yeungnam University, Gyeongsan, South Korea.

Indole and its derivatives have been shown to interfere with the quorum sensing (QS) systems of a wide range of bacterial pathogens. While indole has been previously shown to inhibit QS in , the effects of various indole derivatives on QS, biofilm formation, and virulence of remain unexplored. Hence, in the present study, we investigated the effects of 51 indole derivatives on biofilm formation, QS, and virulence factor production. The results obtained revealed that several indole derivatives (3-indoleacetonitrile, 5-fluoroindole, 6-fluoroindole, 7-fluoroindole, 7-methylindole, 7-nitroindole, 5-iodoindole, 5-fluoro-2-methylindole, 2-methylindole-3-carboxaldehyde, and 5-methylindole) dose-dependently interfered with quorum sensing (QS) and suppressed prodigiosin production, biofilm formation, swimming motility, and swarming motility. Further assays showed 6-fluoroindole and 7-methylindole suppressed fimbria-mediated yeast agglutination, extracellular polymeric substance production, and secretions of virulence factors (e.g., proteases and lipases). QS assays on CV026 confirmed that indole derivatives interfered with QS. The current results demonstrate the antibiofilm and antivirulence properties of indole derivatives and their potentials in applications targeting virulence.
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http://dx.doi.org/10.3389/fmicb.2020.584812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662412PMC
October 2020

Immobilization and Stabilization of Enzyme in Biomineralized Calcium Carbonate Microspheres.

Front Bioeng Biotechnol 2020 9;8:553591. Epub 2020 Oct 9.

Department of Food Biotechnology, Dong-A University, Busan, South Korea.

Biomineralized uniform and well-organized calcium carbonate microspheres were synthesized for enzyme immobilization, and the immobilized enzyme was successfully stabilized. The physicochemical parameters of calcium carbonate were studied using scanning electron microscopy with energy-dispersive X-ray spectroscopy, particle size analysis, X-ray diffraction analysis, Fourier-transform infrared spectroscopy, and surface area measurement. Additionally, Barrett-Joyner-Halenda adsorption/desorption analysis showed that the calcium carbonate microspheres provided efficient mesopore space for enzyme loading. As a model enzyme, carboxyl esterase (CE) was entrapped and then cross-linked to form an enzyme structure. In this aggregate, the cross-linked enzymes cannot leach out from mesopores, resulting in enzyme stability. The hydrolytic activities of the free and cross-linked enzymes were analyzed over broad temperature and pH ranges. The cross-linked enzyme displayed better activity than the free enzyme. Furthermore, the immobilized CE was found to be stable for more than 30 days, preserving 60% of its initial activity even after being reused more than 10 times. This report is expected to be the first demonstration of a stabilized cross-linked enzyme system in calcium carbonate microspheres, which can be applied in enzyme catalyzed reactions involved in bioprocessing, bioremediation, and bioconversion.
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http://dx.doi.org/10.3389/fbioe.2020.553591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581938PMC
October 2020

Enhanced Antibiofilm Effects of N Plasma-Treated Buffer Combined with Antimicrobial Hexapeptides Against Plant Pathogens.

Polymers (Basel) 2020 Sep 1;12(9). Epub 2020 Sep 1.

Department of Biological Science, College of Natural Sciences, Ajou University, 206, World cup-ro, Yeongtong-gu, Suwon, Gyeonggi-do 16499, Korea.

Suppression of pathogenic bacterial growth to increase food and agricultural productivity is important. We previously developed novel hexapeptides (KCM12 and KCM21) with antimicrobial activities against various phytopathogenic bacteria and N plasma-treated buffer (NPB) as an alternative method for bacterial inactivation and as an antibiofilm agent of crops. Here, we developed an enhanced antibiofilm method based on antimicrobial hexapeptides with N plasma-treated buffer against plant pathogens. Our results demonstrated that hexapeptides effectively inhibited the growth of pv. DC3000 ( DC3000) and the biofilm it formed. Potent biofilm formation-inhibiting effects of hexapeptides were observed at concentrations of above 20 µM, and samples treated with hexapeptide above 100 µM reduced the ability of the bacteria to produce biofilm by 80%. 3D confocal laser scanning microscopy imaging data revealed that the antimicrobial activity of hexapeptides was enough to affect the cells embedded inside the biofilm. Finally, combination treatment with NPB and antimicrobial hexapeptides increased the antibiofilm effect compared with the effect of single processing against multilayered plant pathogen biofilms. These findings show that the combination of hexapeptides and NPB can be potentially applied for improving crop production.
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http://dx.doi.org/10.3390/polym12091992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564792PMC
September 2020

Rapid Killing and Biofilm Inhibition of Multidrug-Resistant Strains and Other Microbes by Iodoindoles.

Biomolecules 2020 08 14;10(8). Epub 2020 Aug 14.

School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea.

Multi-drug resistant is well-known for its rapid acclimatization in hospital environments. The ability of the bacterium to endure desiccation and starvation on dry surfaces for up to a month results in outbreaks of health care-associated infections. Previously, indole and its derivatives were shown to inhibit other persistent bacteria. We found that among 16 halogenated indoles, 5-iodoindole swiftly inhibited growth, constrained biofilm formation and motility, and killed the bacterium as effectively as commercial antibiotics such as ciprofloxacin, colistin, and gentamicin. 5-Iodoindole treatment was found to induce reactive oxygen species, resulting in loss of plasma membrane integrity and cell shrinkage. In addition, 5-iodoindole rapidly killed three strains, , and the fungus , but did not inhibit the growth of . This study indicates the mechanism responsible for the activities of 5-iodoindole warrants additional study to further characterize its bactericidal effects on antibiotic-resistant and other microbes.
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http://dx.doi.org/10.3390/biom10081186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465641PMC
August 2020

Diagnostic Accuracy of Quantitative Multi-Contrast 5-Minute Knee MRI Using Prospective Artificial Intelligence Image Quality Enhancement.

AJR Am J Roentgenol 2020 08 5. Epub 2020 Aug 5.

Department of Radiology, Stanford University, 1201 Welch Road, Stanford, California 94305, USA.

Background: Potential approaches for abbreviated knee MRI, including prospective acceleration with deep learning, have achieved limited clinical implementation to date.

Objectives: The objective of this study was to evaluate the inter-reader agreement of conventional knee MRI and a 5-minute 3D quantitative double-echo steady-state (qDESS) sequence with automatic T2 mapping and deep-learning super-resolution (DLSR) augmentation, as well as to compare the diagnostic performance of the two methods with respect to findings from arthroscopic surgery.

Methods: A total of 51 patients with knee pain underwent knee MRI that included an additional 3D qDESS sequence with automatic T2 mapping. Fourier interpolation was followed by prospective DLSR to enhance qDESS slice-resolution twofold. A musculoskeletal radiologist and a radiology resident performed retrospective independent evaluations of the articular cartilage, menisci, ligaments, bones, extensor mechanism, and synovium using conventional MRI. Following a two-month washout period, the readers reviewed qDESS images alone, followed by qDESS with the automatic T2 maps. Inter-reader agreement between conventional MRI and qDESS was computed using percent agreement and Cohen's Kappa. The sensitivity and specificity of conventional MRI, qDESS alone, and qDESS+T2 were compared with arthroscopic findings using exact McNemar's tests.

Results: Conventional MRI and qDESS demonstrated 92% agreement in evaluation of articular cartilage, menisci, ligaments, bones, extensor mechanism, and synovium combined. Kappa was 0.79 (0.76-0.81) across all imaging findings. In the 43/51 patients who underwent arthroscopy, sensitivity and specificity were not significantly different (p=0.23-1.00) between conventional MRI (sensitivity: 58%-93%; specificity: 27%-87%) and qDESS alone (sensitivity: 54%-90%; specificity: 23%-91%) for cartilage, menisci, ligaments, and synovium. Sensitivity and specificity for grade 1 cartilage lesions were 33%/56% for conventional MRI, 23%/53% for qDESS (p=0.81), and 46%/39% for qDESS+T2 (p=0.80); for grade 2A lesions, 27%/53% for conventional MRI, 26%/52% for qDESS (p=0.02), and 58%/40% for qDESS+T2 (p<0.001).

Conclusion: qDESS prospectively enhanced with deep learning had strong inter-reader agreement with conventional knee MRI and near-equivalent diagnostic performance with respect to arthroscopy. The ability of qDESS to automatically generate T2 maps increases sensitivity for cartilage abnormalities. Clinical Impact: qDESS using prospective artificial intelligence image quality enhancement may facilitate an abbreviated knee MRI protocol while generating quantitative T2 maps.
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http://dx.doi.org/10.2214/AJR.20.24172DOI Listing
August 2020

Selection and identification of a novel bone-targeting peptide for biomedical imaging of bone.

Sci Rep 2020 06 29;10(1):10576. Epub 2020 Jun 29.

Korea Institute of Ceramic Engineering and Technology, Center for Convergence Bioceramic Materials, 202 Osongsaengmyeong 1-ro, Cheongjusi, Chungcheongbuk-do, 28160, South Korea.

The global burden of bone-related diseases is increasing in the aging society; thus, improved bone targeted imaging for their early identification and treatment are needed. In this study, we screened novel peptide ligands for hydroxyapatite, a major inorganic component of teeth and bones, and identified a peptide enabling in vivo bone targeting and real-time fluorescence bone detection. To isolate peptides highly specific for hydroxyapatite, we used negative and positive selection from a randomized 8-mer peptide phage library and identified hydroxyapatite-specific peptides (HA-pep2, HA-pep3, and HA-pep7). Among these three peptides, HA-pep3 showed the highest binding capacity and superior dissociation constant towards hydroxyapatite surfaces over time (~ 88.3% retained on hydroxyapatite after two weeks). Furthermore, HA-pep3 was highly specific for hydroxyapatite compared to other calcium salt-based materials. Using this superior specificity, HA-pep3 showed higher accumulation in skull, spine, and joints in comparison with scrambled control peptide during real-time whole-body imaging. Ex vivo analysis of the major organs and bone from mice demonstrated that the fluorescence intensity in bone was about 3.32 folds higher in the case of HA-pep3 than the one exhibited by the scrambled control peptide. Our study identified a novel approach for targeting ligands for bone specific imaging and can be useful for drug delivery applications.
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http://dx.doi.org/10.1038/s41598-020-67522-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324617PMC
June 2020

Fatty Acids as Antibiofilm and Antivirulence Agents.

Trends Microbiol 2020 09 28;28(9):753-768. Epub 2020 Apr 28.

School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea. Electronic address:

Fatty acids (FAs) have emerged as a potential alternative to conventional antibiotics. Since many microbes respond differently to a variety of natural and synthetic FAs, substantial efforts have been made to understand the unique features of FAs that function as antimicrobials at high doses and biofilm inhibitors at low doses. Here, we provide an overview of the emerging antibiofilm properties of FAs and their relations to virulence and quorum sensing, such as diffusible signal factors (DSFs), acyl-homoserine lactones, and autoinducer-2 systems. Several FAs mimic DSFs and control motility, fimbriae, hyphae, and biofilm development as well as virulence characteristics of diverse microbes. The findings of FAs as antibiofilm and antivirulence agents will provide a new paradigm to cope with recalcitrant pathogens.
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http://dx.doi.org/10.1016/j.tim.2020.03.014DOI Listing
September 2020

Construction of Alizarin Conjugated Graphene Oxide Composites for Inhibition of Biofilms.

Biomolecules 2020 04 7;10(4). Epub 2020 Apr 7.

School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea.

Biofilm inhibition using nanoparticle-based drug carriers has emerged as a noninvasive strategy to eradicate microbial contaminants such as fungus . In this study, one-step adsorption strategy was utilized to conjugate alizarin (AZ) on graphene oxide (GO) and characterized by ultraviolet-visible spectroscopy (UV-Vis), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray powder diffraction (XRD), dynamic light-scattering (DLS), and transmission electron microscopy (TEM). Crystal violet assay was performed to evaluate the antibiofilm efficacy of GO-AZs against . Different characterizations disclosed the loading of AZ onto GO. Interestingly, TEM images indicated the abundant loading of AZ by producing a unique inward rolling of GO-AZ sheets as compared to GO. When compared to the nontreatment, GO-AZ at 10 µg/mL significantly reduced biofilm formation to 96% almost equal to the amount of AZ (95%). It appears that the biofilm inhibition is due to the hyphal inhibition of . The GO is an interesting nanocarrier for loading AZ and could be applied as a novel antibiofilm agent against various microorganisms including .
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http://dx.doi.org/10.3390/biom10040565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226399PMC
April 2020

Predicting Successful Generation and Inhibition of Seizure-like Afterdischarges and Mapping Their Seizure Networks Using fMRI.

Cell Rep 2020 02;30(8):2540-2554.e4

Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA. Electronic address:

To understand the conditions necessary to initiate and terminate seizures, we investigate optogenetically induced hippocampal seizures with LFP, fMRI, and optogenetic inhibition. During afterdischarge induction using optogenetics, LFP recordings show that stimulations with earlier ictal onset times are more likely to result in afterdischarges and are more difficult to curtail with optogenetic inhibition. These results are generalizable across two initiation sites, the dorsal and ventral hippocampus. fMRI shows that afterdischarges initiated from the dorsal or ventral hippocampus exhibit distinct networks. Short-duration seizures initiated in the dorsal and ventral hippocampus are unilateral and bilateral, respectively, while longer-duration afterdischarges recruit broader, bilateral networks. When optogenetic inhibition is ineffective at stopping seizures, the network activity spreads more extensively but largely overlaps with the network activity associated with seizures that could be curtailed. These results provide insights into how seizures can be inhibited, which has implications for targeted seizure interventions.
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http://dx.doi.org/10.1016/j.celrep.2020.01.095DOI Listing
February 2020

Inhibition of and biofilms by centipede oil and linoleic acid.

Biofouling 2020 02 24;36(2):126-137. Epub 2020 Feb 24.

School of Chemical Engineering, Yeungnam University, Gyeongsan, Republic of Korea.

Microbial biofilms are associated with persistent infections because of their high tolerance to antimicrobial agents and host defenses. The effects of centipede oil from and its main components were investigated to identify non-toxic biofilm inhibitors. Centipede oil and linoleic acid at 20 µg ml markedly inhibited biofilm formation by two fluconazole-resistant strains and three strains without affecting their planktonic cell growth. Also, both centipede oil and linoleic acid inhibited hyphal growth and cell aggregation by . In addition, centipede oil and linoleic acid showed anti-biofilm activities against mixed and biofilms. Transcriptomic analysis showed that centipede oil and linoleic acid downregulated the expressions of several hypha/biofilm-related genes in and α-hemolysin in . Furthermore, both compounds effectively reduced virulence in a nematode infection model with minimal toxicity.
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http://dx.doi.org/10.1080/08927014.2020.1730333DOI Listing
February 2020

Thalamic Input to Orbitofrontal Cortex Drives Brain-wide, Frequency-Dependent Inhibition Mediated by GABA and Zona Incerta.

Neuron 2019 12 23;104(6):1153-1167.e4. Epub 2019 Oct 23.

Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, CA 94305, USA. Electronic address:

Anatomical and behavioral data suggest that the ventrolateral orbitofrontal cortex (VLO), which exhibits extensive connectivity and supports diverse sensory and cognitive processes, may exert global influence over brain activity. However, this hypothesis has never been tested directly. We applied optogenetic fMRI to drive various elements of VLO circuitry while visualizing the whole-brain response. Surprisingly, driving excitatory thalamocortical projections to VLO at low frequencies (5-10 Hz) evoked widespread, bilateral decreases in brain activity spanning multiple cortical and subcortical structures. This pattern was unique to thalamocortical projections, with direct stimulations of neither VLO nor thalamus eliciting such a response. High-frequency stimulations (25-40 Hz) of thalamocortical projections evoked dramatically different-though still far-reaching-responses, in the form of widespread ipsilateral activation. Importantly, decreases in brain activity evoked by low-frequency thalamocortical input were mediated by GABA and activity in zona incerta. These findings identify specific circuit mechanisms underlying VLO control of brain-wide neural activities.
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http://dx.doi.org/10.1016/j.neuron.2019.09.023DOI Listing
December 2019

Life-threatening bleeding with intussusception due to gastrointestinal stromal tumor: a case report.

Surg Case Rep 2019 Oct 24;5(1):154. Epub 2019 Oct 24.

Department of Internal Medicine, Soonchunhyang University Hospital, Gumi, South Korea.

Background: Massive intraluminal bleeding requires urgent intervention and management. However, the source of bleeding on the small intestine is difficult to determine. Intestinal tumor with intussusception is a rare and normally not an urgent condition. Herein, we present a rare case of intestinal intussusception with massive bleeding due to jejunal gastrointestinal stromal tumor (GIST) that required emergency surgical treatment.

Case Presentation: A 51-year-old male was admitted to the emergency department complaining of abdominal pain and acute hematochezia. Esophagogastroduodenoscopy (EGD) and colonoscopy could not determine the source of the bleeding site. Abdominal pelvic computed tomography (AP-CT) revealed GIST with intussusception, strongly suggestive of distal jejunal bleeding. Unresponsive transfusion with low blood pressure and continuous hematochezia led to emergency laparotomy. GIST, which was the leading point for intussusception, was located in the jejunum and showed mucosal ulceration of approximately 3.5 cm in diameter. Following resection and functional anastomosis, histology revealed a GIST with low mitotic count (< 5 per 50HPF). Moreover, immunochemical analysis revealed positivity for c-kit (CD117) and DOG-1. There were no complications 2 months after surgery.

Conclusions: Intussusception associated with GIST is a rare finding that can be life-threatening if it occurs with an ulcer. This case showed that the early detection of bleeding and emergency surgery could prevent severe complications.
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http://dx.doi.org/10.1186/s40792-019-0703-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813375PMC
October 2019

The anti-biofilm and anti-virulence activities of resveratrol and oxyresveratrol against uropathogenic .

Biofouling 2019 08 10;35(7):758-767. Epub 2019 Sep 10.

School of Chemical Engineering, Yeungnam University , Gyeongsan , Republic of Korea.

Uropathogenic (UPEC) is the primary causative agent of urinary tract infections, which are one of the most common infectious disease types in humans. UPEC infections involve bacterial cell adhesion to bladder epithelial cells, and UPEC can also form biofilms on indwelling catheters that are often tolerant to common antibiotics. In this study, the anti-biofilm activities of -stilbene, stilbestrol, -resveratrol, oxyresveratrol, -viniferin, suffruticosol A, and vitisin A were investigated against UPEC. -Resveratrol, oxyresveratrol, and -viniferin, suffruticosol A, and vitisin A significantly inhibited UPEC biofilm formation at subinhibitory concentrations (10-50 μg ml). These findings were supported by observations that -resveratrol and oxyresveratrol reduced fimbriae production and the swarming motility in UPEC. Furthermore, -resveratrol and oxyresveratrol markedly diminished the hemagglutinating ability of UPEC, and enhanced UPEC killing by human whole blood. The findings show that -resveratrol, oxyresveratrol, and resveratrol oligomers warrant further attention as antivirulence strategies against persistent UPEC infections.
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http://dx.doi.org/10.1080/08927014.2019.1657418DOI Listing
August 2019

Antimicrobial and antibiofilm activities of prenylated flavanones from Macaranga tanarius.

Phytomedicine 2019 Oct 13;63:153033. Epub 2019 Jul 13.

School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address:

Background: The emergence of antibiotic resistant microorganisms presents a worldwide problem that requires novel antibiotic and non-antibiotic strategies, and biofilm formation is a mechanism of drug resistance utilized by diverse microorganisms. The majority of microorganisms live in biofilms that help their survival against starvation, antimicrobial agents, and immunological defense systems. Therefore, it is important novel compounds be identified that inhibit biofilm formation and cell survival without drug resistance.

Study Design: In this study, the antimicrobial and antibiofilm activities of five prenylated flavanones (Okinawan propolins) isolated from fruits of Macaranga tanarius (L.) were investigated against 14 microorganisms including 10 pathogens.

Results: Of these five propolins, propolin D at 5-10 µg/ml significantly inhibited biofilm formation by three Staphylococcus aureus strains, a Staphylococcus epidermidis strain, and a Candida albicans with MICs from 10 to 50 µg/ml, and in C. albicans, propolin D was found to inhibit biofilm formation by reducing cell aggregation and downregulated the expressions of hypha/biofilm-related genes including ECE1 and HWP1. Interestingly, at sub-MIC concentrations (10-50 µg/ml), propolin D significantly inhibited biofilm formation by enterohemorrhagic E. coli O157:H7, uropathogenic E. coli O6:H1, and Acinetobacter baumannii without affecting planktonic cell growth, but did not inhibit biofilm formation by a commensal E. coli K-12 strain, three probiotic Lactobacillus plantarum strains, or two Pseudomonas aeruginosa strains. And, propolin D reduced fimbriae production by E. coli O157:H7 and repressed gene expression of curli fimbriae genes (csgA and csgB). Also, propolin D was minimally toxic in a Caenorhabditis elegans nematode model.

Conclusion: These findings show that prenylated flavanones, especially propolin D from Macaranga tanarius (Okinawan propolis), should be considered potential candidates for the development of non-toxic antibacterial and antifungal agents against persistent microorganisms.
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http://dx.doi.org/10.1016/j.phymed.2019.153033DOI Listing
October 2019

Synergistic antioxidant activity of size controllable chitosan-templated Prussian blue nanoparticle.

Nanomedicine (Lond) 2019 10 19;14(19):2567-2578. Epub 2019 Jul 19.

Center for Convergence Bioceramic Materials, Convergence R&D Division, Korea Institute of Ceramic Engineering & Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea.

Prussian blue nanoparticles (PB NPs) have been reported as excellent antioxidant agents owing to their ability to scavenge reactive oxygen species. However, their poor stability limits their use in biomedical applications. In this study, we developed chitosan-templated PB NPs using water-soluble chitosan samples with molecular weights ranging from 3 to 100 kDa, which stabilized the PB NPs and improved their antioxidant activity. The chitosan-templated PB NPs coordinated with the optimal chitosan molecular weight had uniform sphere-like particles, improved stability and effective scavenging activity of  reactive oxygen species generation in murine fibroblast cells stimulated by oxidative stress agents without any cytotoxicity, implying that they could be promising antioxidant agents.
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http://dx.doi.org/10.2217/nnm-2019-0223DOI Listing
October 2019

Utility of deep learning super-resolution in the context of osteoarthritis MRI biomarkers.

J Magn Reson Imaging 2020 03 16;51(3):768-779. Epub 2019 Jul 16.

Department of Radiology, Stanford University, Stanford, California, USA.

Background: Super-resolution is an emerging method for enhancing MRI resolution; however, its impact on image quality is still unknown.

Purpose: To evaluate MRI super-resolution using quantitative and qualitative metrics of cartilage morphometry, osteophyte detection, and global image blurring.

Study Type: Retrospective.

Population: In all, 176 MRI studies of subjects at varying stages of osteoarthritis.

Field Strength/sequence: Original-resolution 3D double-echo steady-state (DESS) and DESS with 3× thicker slices retrospectively enhanced using super-resolution and tricubic interpolation (TCI) at 3T.

Assessment: A quantitative comparison of femoral cartilage morphometry was performed for the original-resolution DESS, the super-resolution, and the TCI scans in 17 subjects. A reader study by three musculoskeletal radiologists assessed cartilage image quality, overall image sharpness, and osteophytes incidence in all three sets of scans. A referenceless blurring metric evaluated blurring in all three image dimensions for the three sets of scans.

Statistical Tests: Mann-Whitney U-tests compared Dice coefficients (DC) of segmentation accuracy for the DESS, super-resolution, and TCI images, along with the image quality readings and blurring metrics. Sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals compared osteophyte detection for the super-resolution and TCI images, with the original-resolution as a reference.

Results: DC for the original-resolution (90.2 ± 1.7%) and super-resolution (89.6 ± 2.0%) were significantly higher (P < 0.001) than TCI (86.3 ± 5.6%). Segmentation overlap of super-resolution with the original-resolution (DC = 97.6 ± 0.7%) was significantly higher (P < 0.0001) than TCI overlap (DC = 95.0 ± 1.1%). Cartilage image quality for sharpness and contrast levels, and the through-plane quantitative blur factor for super-resolution images, was significantly (P < 0.001) better than TCI. Super-resolution osteophyte detection sensitivity of 80% (76-82%), specificity of 93% (92-94%), and DOR of 32 (22-46) was significantly higher (P < 0.001) than TCI sensitivity of 73% (69-76%), specificity of 90% (89-91%), and DOR of 17 (13-22).

Data Conclusion: Super-resolution appears to consistently outperform naïve interpolation and may improve image quality without biasing quantitative biomarkers.

Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:768-779.
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http://dx.doi.org/10.1002/jmri.26872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962563PMC
March 2020

Application of red-mud based ceramic media for phosphate uptake from water and evaluation of their effects on growth of Iris latifolia seedling.

Sci Total Environ 2019 Oct 19;688:724-731. Epub 2019 Jun 19.

Department of Environmental Engineering, University of Seoul, Seoul, Republic of Korea. Electronic address:

In the present study, we have produced red-mud based ceramic media (RMCM) as an adsorbent for removal of phosphate from aqueous solutions, and their application in a constructed wetland. Phosphate adsorption to RMCM was investigated by varying initial phosphate concentration, contact time, and temperature. Adsorption of phosphate to the surface of RMCM was confirmed by scanning electron microscope and energy dispersive X-ray spectroscopy. The surface area and pore volume of RMCM decreased significantly after phosphate adsorption. Experimental equilibrium data followed Langmuir and Sips model better than the Freundlich model. Kinetic data followed both pseudo first order and pseudo second order reactions. Thermodynamics suggested the phosphate adsorption process onto RMCM to be endothermic and spontaneous, and physisorption dominated. Fourier transform infrared spectrumof phosphate adsorbed RMCM did not show any PO specific bands thus ruling out role of chemical forces in phosphate adsorption. Overall, phosphate adsorption on RMCM was driven by physisorption. The RMCM promoted biomass growth and increased the surface area of roots in Iris latifolia. Together with RMCM, I. latifolia augmented removal of phosphate from aqueous solution. Based on their phosphate removal performance and plant-growth promoting effects, we believe that RMCM can be effectively used in constructed wetlands.
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http://dx.doi.org/10.1016/j.scitotenv.2019.06.267DOI Listing
October 2019

Aripiprazole repurposed as an inhibitor of biofilm formation and sterol biosynthesis in multidrug-resistant Candida albicans.

Int J Antimicrob Agents 2019 Oct 5;54(4):518-523. Epub 2019 Jun 5.

School of Chemical Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea. Electronic address:

Drug repurposing is an anticipative chemotherapeutic strategy that accentuates the inadequacy of antifungal drugs. The study identifies an antipsychotic drug, aripiprazole, as a biofilm and hyphal inhibitor of Candida albicans. Microtitre plate biofilm inhibition, metabolic activity and hyphal inhibitory assays were used to assess the potency of aripiprazole; and filipin staining, reactive oxygen species staining, cAMP rescue, propidium iodide staining, computational studies and qRT-PCR assays were used to elucidate its mode of action. The study revealed aripiprazole functioned in a manner similar to standard azoles, particularly the imidazole, ketoconazole, by inhibiting pseudohyphal formation during the early stages of hyphal development. The action of aripiprazole on C. albicans was dose-dependent and it exhibited varied mechanisms of action at low and high dosages. At low dosage, aripiprazole outperformed ketoconazole in terms of inhibiting biofilm formation, hyphal filamentations, and yeast flocculation, whereas at higher dosage it mimicked ketoconazole. This study illustrates the anti-candidal potential and mechanistic activities of aripiprazole, and indicates the future use of this drug as an anti-biofilm agent.
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http://dx.doi.org/10.1016/j.ijantimicag.2019.05.016DOI Listing
October 2019

Antibiofilm and Antivirulence Efficacies of Flavonoids and Curcumin Against .

Front Microbiol 2019 8;10:990. Epub 2019 May 8.

School of Chemical Engineering, Yeungnam University, Gyeongsan, South Korea.

is well adapted to hospital environments, and the persistence of its chronic infections is mainly due to its ability to form biofilms resistant to conventional antibiotics and host immune systems. Hence, the inhibitions of biofilm formation and virulence characteristics provide other means of addressing infections. In this study, the antibiofilm activities of twelve flavonoids were initially investigated. Three most active flavonoids, namely, fisetin, phloretin, and curcumin, dose-dependently inhibited biofilm formation by a reference strain and by several clinical isolates, including four multidrug-resistant isolates. Furthermore, the antibiofilm activity of curcumin (the most active flavonoid) was greater than that of the well-known biofilm inhibitor gallium nitrate. Curcumin inhibited pellicle formation and the surface motility of . Interestingly, curcumin also showed antibiofilm activity against and mixed cultures of and . molecular docking of the biofilm response regulator BfmR showed that the binding efficacy of flavonoids with BfmR was correlated with antibiofilm efficacy. In addition, curcumin treatment diminished virulence in an model without cytotoxicity. The study shows curcumin and other flavonoids have potential for controlling biofilm formation by and the virulence of .
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http://dx.doi.org/10.3389/fmicb.2019.00990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517519PMC
May 2019

Inhibition of Biofilm Formation by and Polymicrobial Microorganisms by Nepodin via Hyphal-Growth Suppression.

ACS Infect Dis 2019 07 10;5(7):1177-1187. Epub 2019 May 10.

School of Chemical Engineering , Yeungnam University , 280 Daehak-Ro , Gyeongsan 38541 , Republic of Korea.

is an opportunistic pathogenic yeast and is responsible for candidiasis. It readily colonizes host tissues and implant devices, and forms biofilms, which play an important role in pathogenesis and drug resistance. In this study, the antibiofilm, antihyphal, and antivirulence activities of nepodin, isolated from roots, were investigated against a fluconazole-resistant strain and against polymicrobial-microorganism-biofilm formation. Nepodin effectively inhibited biofilm formation without affecting its planktonic cell growth. Also, -root extract and nepodin both inhibited hyphal growth and cell aggregation of . Interestingly, nepodin also showed antibiofilm activities against , , , and strains and against dual biofilms of and or but not against . Transcriptomic analysis performed by RNA-seq and qRT-PCR showed nepodin repressed the expression of several hypha- and biofilm-related genes (, , , and ) and increased the expression of several transport genes (, , and ), which supported phenotypic changes. Moreover, nepodin reduced virulence in a nematode-infection model and exhibited minimal cytotoxicity against the nematode and an animal cell line. These results demonstrate that nepodin and -root extract might be useful for controlling infections and multispecies biofilms.
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http://dx.doi.org/10.1021/acsinfecdis.9b00033DOI Listing
July 2019

Nematicidal and insecticidal activities of halogenated indoles.

Sci Rep 2019 02 14;9(1):2010. Epub 2019 Feb 14.

School of Chemical Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea.

Parasite death via ion channel activations is the hallmark of anthelmintic and antiparasitic drugs. Glutamate gated chloride channel (GluCl) is a prominent targets for drug selection and design in parasitology. We report several iodine-fluorine based lead activators of GluCl by computational studies and structure-activity relationship analysis. 5-Fluoro-4-iodo-1H-pyrrolo [2, 3-b] pyridine and 5-iodoindole were bioactive hits that displayed in vitro anthelmintic and insecticidal activities against Bursaphelenchus xylophilus, Meloidogyne incognita, and Tenebrio molitor. Two important findings stood out: (i) 5F4IPP induced parasite death, and interacted proficiently with Gln amino acid of pentameric GluCl in docking analysis, and (ii) 5-iodoindole appeared to act by forming giant vacuoles in nematodes, which led to a form of non-apoptotic death known as methuosis. The study suggests halogenated-indoles and 1H-pyrrolo [2, 3-b] pyridine derivatives be regarded potential biocides for plant-parasitic nematodes and insects, and warrants further research on the mode of actions, and field investigations.
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http://dx.doi.org/10.1038/s41598-019-38561-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375993PMC
February 2019

Suppression of Fluconazole Resistant Biofilm Formation and Filamentation by Methylindole Derivatives.

Front Microbiol 2018 6;9:2641. Epub 2018 Nov 6.

School of Chemical Engineering, Yeungnam University, Gyeongsan, South Korea.

is an opportunistic fungal pathogen and most prevalent species among clinical outbreaks. It causes a range of infections, including from mild mucosal infections to serious life-threatening candidemia and disseminated candidiasis. Multiple virulence factors account for the pathogenic nature of , and its morphological transition from budding yeast to hyphal form and subsequent biofilm formation is regarded as the most important reason for the severity of infections. To address the demanding need for novel antifungals, we investigated the anti-biofilm activities of various methylindoles against using a crystal violet assay, and the metabolic activity was assessed by using a 2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide reduction assay. Changes in biofilm morphologies and thicknesses were determined by confocal laser scanning microscopy and scanning electron microscopy, respectively. Of the 21 methylindoles tested, 1-methylindole-2-carboxylic acid (1MI2CA) at 0.1 mM (17.5 μg ml) and 5-methylindole-2-carboxylic acid (5MI2CA) at 0.1 mM effectively inhibited biofilm formation by DAY185 and ATCC10231 strains. Moreover, 1MI2CA and 5MI2CA both effectively inhibited hyphal formation, and thus, improved infected nematode survival without inducing acute toxic effects. Furthermore, our molecular modeling findings were in-line with observations. This study provides information useful for the development of novel strategies targeting candidiasis and biofilm-related infections.
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http://dx.doi.org/10.3389/fmicb.2018.02641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232606PMC
November 2018

Carbon monofilament electrodes for unit recording and functional MRI in same subjects.

Neuroimage 2019 02 2;186:806-816. Epub 2018 Nov 2.

Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, USA; Department of Neurosurgery, Stanford University, USA; Department of Electrical Engineering, Stanford University, USA. Electronic address:

Extracellular electrophysiology and functional MRI are complementary techniques that provide information about cellular and network-level neural activity, respectively. However, electrodes for electrophysiology are typically made from metals, which cause significant susceptibility artifacts on MR images. Previous work has demonstrated that insulated carbon fiber bundle electrodes reduce the volume of magnetic susceptibility artifacts and can be used to record local field potentials (LFP), but the relatively large diameter of the probes make them unsuitable for multi- and single-unit recordings. Although single carbon fiber electrodes have recently been used to record single-unit activity, these probes require modifications in order to aid insertion and the use of these probes in fMRI has yet to be validated. Therefore, there is a need for a single-carbon fiber electrode design that (1) minimizes the volume of the susceptibility artifact, (2) can record from a wide frequency band that includes LFP and multi- and single-unit recording, and (3) is practical to insert without additional modifications. Here, we demonstrate that carbon-fiber electrodes made from single carbon monofilaments (35 μm in diameter) meet all of these criteria. Carbon monofilament electrodes modified with the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) have lower impedances and higher signal-to-noise ratio recordings than platinum-iridium electrodes, a current gold standard for chronic single-unit recording. Furthermore, these probes distort a significantly smaller volume of voxels compared to tungsten and platinum-iridium electrodes in agarose phantom and in vivo MR images, leading to higher contrast-to-noise ratio in regions proximal to the electrode implantation site during fMRI. Collectively, this work establishes that carbon monofilaments are a practical choice for combined electrophysiology-fMRI experiments.
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http://dx.doi.org/10.1016/j.neuroimage.2018.10.082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458097PMC
February 2019

Antibiofilm and Antivirulence Activities of 6-Gingerol and 6-Shogaol Against Due to Hyphal Inhibition.

Front Cell Infect Microbiol 2018 28;8:299. Epub 2018 Aug 28.

School of Chemical Engineering, Yeungnam University, Gyeongsan, South Korea.

is an opportunistic pathogen and responsible for candidiasis. readily forms biofilms on various biotic and abiotic surfaces, and these biofilms can cause local and systemic infections. biofilms are more resistant than its free yeast to antifungal agents and less affected by host immune responses. Transition of yeast cells to hyphal cells is required for biofilm formation and is believed to be a crucial virulence factor. In this study, six components of ginger were investigated for antibiofilm and antivirulence activities against a fluconazole-resistant strain. It was found 6-gingerol, 8-gingerol, and 6-shogaol effectively inhibited biofilm formation. In particular, 6-shogaol at 10 μg/ml significantly reduced biofilm formation but had no effect on planktonic cell growth. Also, 6-gingerol and 6-shogaol inhibited hyphal growth in embedded colonies and free-living planktonic cells, and prevented cell aggregation. Furthermore, 6-gingerol and 6-shogaol reduced virulence in a nematode infection model without causing toxicity at the tested concentrations. Transcriptomic analysis using RNA-seq and qRT-PCR showed 6-gingerol and 6-shogaol induced several transporters (, and ), but repressed the expressions of several hypha/biofilm related genes ( and ), which supported observed phenotypic changes. These results highlight the antibiofilm and antivirulence activities of the ginger components, 6-gingerol and 6-shogaol, against a drug resistant strain.
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http://dx.doi.org/10.3389/fcimb.2018.00299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121036PMC
August 2019

Epicardial Fat Thickness and Free Fatty Acid Level are Predictors of Acute Ischemic Stroke with Atrial Fibrillation.

J Cardiovasc Imaging 2018 Jun 12;26(2):65-74. Epub 2018 Jun 12.

Department of Neurology, Kosin University College of Medicine, Busan, Korea.

Background: Increased epicardial fat is known to be associated with the presence and chronicity of atrial fibrillation (AF). Free fatty acids (FFAs) are major components of epicardial fat; however, their potential association with AF in ischemic stroke has not been investigated. We aimed to assess the performance of echocardiographic epicardial fat thickness (EFT) and plasma FFA level in identifying patients with ischemic stroke and AF.

Methods: We enrolled a total of 214 consecutive patients (mean age, 66.8 ± 12.3 years; 39.7% women) diagnosed with acute ischemic stroke between March 2011 and June 2014. The patients were divided into two groups: ischemic stroke with AF (n = 35, 16.4%) and ischemic stroke without AF (n = 179, 83.6%).

Results: The ischemic stroke with AF group showed significantly higher serum FFA level (1379.7 ± 717.5 vs. 757.8 ± 520.5 uEq/L, < 0.0001) and EFT (6.5 ± 1.2 vs. 5.3 ± 1.2 mm, < 0.001) than the group without AF. Multivariable logistic regression analysis demonstrated that age (odds ratio [OR], 1.112), serum FFA level (OR, 1.002), and EFT (OR, 1.740) were independently associated with the ischemic stroke group with AF. EFT and FFA significantly improved the goodness-of-fit and discriminability of the simple regression model including age as a covariate (log likelihood difference, 21.35; < 0.001; c-index difference, 17.9%; < 0.001).

Conclusions: High EFT and serum FFA level were associated with ischemic stroke in patients with AF. Echocardiographic EFT and serum FFA level can play a significant role in identifying ischemic stroke with AF.
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http://dx.doi.org/10.4250/jcvi.2018.26.e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024837PMC
June 2018