Publications by authors named "Joon-Hee Lee"

122 Publications

Water Ski Injuries and Chronic Pain in Collegiate Athletes.

Int J Environ Res Public Health 2021 Apr 9;18(8). Epub 2021 Apr 9.

Department of Kinesiology, College of Health Sciences, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA.

This study examined the rate of injuries and chronic pain in collegiate water-ski athletes as a preliminary study. We also compared the mechanics and cause of injuries by the level of water-skiing experiences. A total number of 96 collegiate water-ski athletes, aged 21.4 ± 2.23 years, participated in the study. An off-line questionnaire was distributed at the collegiate tournaments in the United States. The questionnaire consisted of 20 questions, including demographic information, body region and type of injuries, mechanics and cause of injuries, chronic pain and pain management. A Chi-squared test was used to examine the differences in injury rates by sex and the level of experiences (beginner: <5 years, intermediate: 5-10 years, advanced: <10 years). The significance level was set at ≤0.05. A total of 336 water skiing-related injuries were observed from 96 participants. The ankle/feet, knee, and head/neck regions were the most common body regions injured, representing 26.5, 16.7, and 15.8%, respectively. Female athletes were more likely to have nerve injuries than male athletes ( = 0.039). The intermediate athletes were more likely to have trunk ( = 0.047) and upper extremity ( = 0.042) injuries than beginner athletes, and the beginner athletes had less joint/ligament ( = 0.001) and bone injury ( = 0.010) compared to the advanced athletes. Torsion/twisting (32.8%) and deceleration (26.9%) were the most common mechanism of injury. Beginner athletes experienced injuries more due to insufficient skill ( = 0.03), while the advanced athletes were likely to have more injuries by the loss of control ( = 0.01). Collegiate athletes had higher rates of chronic pain in the trunk (42.7%) and skeletal muscle (43.8%), and they participated in stretching/exercise (40.8%) and massage/form rolling (29.6%) to manage their chronic pain. The present study revealed that injury rates in males and females were 49.7% and 50.2%, respectively. Female athletes were more likely to have a nerve injury than male athletes. The mechanics and cause of injuries were different by the level of experiences where different training approaches may be required to minimize the injuries. Additionally, the strength and conditioning program that is systematically designed for core strength is needed to eliminate chronic trunk pain in collegiate water-skiing athletes.
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http://dx.doi.org/10.3390/ijerph18083939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069366PMC
April 2021

Endothelial Cells Differentiated from Porcine Epiblast Stem Cells.

Cell Reprogram 2021 Apr;23(2):89-98

Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, Republic of Korea.

Pluripotent stem cells (PSCs) have the ability of self-renewal that can retain the characteristics of the mother cell, and of pluripotency that can differentiate into several body types. PSCs typically include embryonic stem cells (ESCs) derived from the inner cell mass of the preimplantation embryo, and epiblast stem cells (EpiSCs) derived from the epiblast of postimplantation embryo. Although PSCs are able to be used by differentiation into endothelial cells as a potential treatment for vascular diseases, human ESCs and induced PSCs (iPSCs) are followed by ethical and safety issues. Pigs are anatomically and physiologically similar to humans. Therefore, the goal of this study was to establish an efficient protocol that differentiates porcine EpiSCs (pEpiSCs) into the endothelial cells for applying the treatment of human vascular diseases. As a result, alkaline phosphatase (AP)-negative (-) pEpiSCs cultured in endothelial cell growth basal medium-2 (EBM-2) differentiation medium in association with 50 ng/mL of vascular endothelial growth factor (VEGF) for 8 days were changed morphologically like the feature of endothelial cells, and expression of pluripotency-associated markers (OCT-3/4, NANOG, SOX2, and C-MYC) in porcine differentiated cells was significantly decreased ( < 0.05). Additionally, when pEpiSCs were cultured in EBM-2 + 50 ng/mL of VEGF, porcine differentiated cells represented a common endothelial cell marker positive (CD31+) but monocytes and lymphocytes marker negative (CD45-). Therefore, these results indicated that pEpiSCs cultured in EBM-2 + 50 ng/mL of VEGF culture condition were efficiently differentiated into endothelial cells for the treatment of blood vessel diseases.
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http://dx.doi.org/10.1089/cell.2020.0088DOI Listing
April 2021

Highly Transparent, Robust Hydrophobic, and Amphiphilic Organic-Inorganic Hybrid Coatings for Antifogging and Antibacterial Applications.

ACS Appl Mater Interfaces 2021 Feb 28;13(5):6615-6630. Epub 2021 Jan 28.

Department of Polymer Science and Engineering, Pusan National University, Busan 46241, Korea.

The control of surface wettability through a combination of surface roughness, chemical composition, and structural modification has attracted significant attention for antifogging and antibacterial applications. Herein, a two-step spin-coating method for amphiphilic organic-inorganic hybrid materials with incorporated transition metal ions is presented. The coating solution was prepared via photochemical thiol-ene click reaction between the mercapto functional group in trimethylolpropane tris(3-mercaptopropionate) and the vinyl functionalized silica precursor 3-(trimethoxysilyl)propyl methacrylate. In the first step of coating, a glass substrate was coated using a solution of metal nitrate hydrates and subsequently showed hydrophobic properties. As the second step, the spin-coated glass substrate was further coated with silica nanoparticles (SiO NPs) and polycaprolactone triol (PCT) suspension, where the contents of SiO NPs were fixed at 0.1 wt %, unless otherwise noted. The coated substrate exhibited hydrophilic properties. For comparison, the coating was also formulated with the SiO NPs/PCT suspension without SiO NPs and with 0.5 wt % SiO NPs as well as by adjusting different coating layer thicknesses. The surface morphology and chemical compositions of the obtained coating materials were analyzed by field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The transparency and static contact angle of coated samples were measured by UV-visible spectrophotometry and drop shape analysis, respectively. It was concluded that our novel hybrid coating materials exhibited excellent antibacterial and antifogging properties with extremely high scratch resistance and transparency.
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http://dx.doi.org/10.1021/acsami.0c20401DOI Listing
February 2021

Suppressive Effect of CYM50358 S1P Antagonist on Mast Cell Degranulation and Allergic Asthma in Mice.

Biomol Ther (Seoul) 2021 Jan 27. Epub 2021 Jan 27.

College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model . S1P functions were evaluated following treatment of CYM50358, a selective antagonist of S1P, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid-Schiff)-stained cells in the lungs. The pro-allergic functions of S1P were elucidated using mast cells and ovalbumin-induced allergic asthma model experiments. These results suggest that S1P antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.
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http://dx.doi.org/10.4062/biomolther.2020.206DOI Listing
January 2021

Analytical performance evaluation of the Norudia HbA assay.

J Clin Lab Anal 2020 Nov 9;34(11):e23504. Epub 2020 Aug 9.

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Hemoglobin A (HbA) is arguably the most important biomarker used in the diagnosis and treatment monitoring of diabetes mellitus. We evaluated the analytical performance of the Norudia HbA assay (Sekisui Medical Co., LTD), which uses an enzymatic method incorporated into a fully automated, high-throughput system.

Methods: The precision, linearity, and carryover of the Norudia HbA assay were evaluated. Using 60 patient samples, comparative analysis of HbA measurements with two commonly used HbA assays, the D100 (Bio-Rad Laboratories, Inc) and HLC-723 G11 (Tosoh), was undergone. Thirteen commutable samples with known HbA concentrations measured using an IFCC reference measurement procedure were used to compare accuracy between methods. Interference of HbA measurement by Hb variants was evaluated using 16 known Hb variant samples.

Results: Repeatability (% CV) for low and high concentrations ranged from 1.12%-1.50% and 0.66%-0.75%, respectively, and within-laboratory precision for low and high concentrations ranged from 1.73%-2.89% and 0.98%-1.64%, respectively. For linearity, the coefficient of determination was 0.9987. No significant carryover was observed. When compared to the D100 and HLC-723 G11 assays, the Norudia HbA assay showed the best accuracy with the lowest mean bias (-1.72%). Furthermore, the Norudia was least affected by Hb variants and gave the most reliable HbA measurements.

Conclusion: The Norudia HbA showed excellent analytical performance with good precision and linearity, and minimal carryover. When compared to other routine HbA methods, the Norudia HbA assay showed the highest accuracy and was least affected by Hb variants.
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http://dx.doi.org/10.1002/jcla.23504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676213PMC
November 2020

Evaluation of analytical performance of Alinity i system on 31 measurands.

Pract Lab Med 2020 Nov 20;22:e00185. Epub 2020 Oct 20.

Department of Laboratory Medicine, Seoul National University Hospital, Seoul, South Korea.

Introduction: Accurate, precise and reliable laboratory test results play a critical role in medical decision making. To satisfy the increasing needs in clinical laboratory tests, the analyzers have been advanced. In this study, authors aimed to evaluate the analytical performance of the Alinity i system (Abbott Laboratories, IL, USA) for diverse analytes measured by using immunoassay principle.

Materials And Methods: Analytical performance of recently launched Alinity i system has been evaluated for 31 assays in aspects of precision, linearity and analytical measurement range, correlation with the Architect i2000sr system (Abbott Laboratories), carry-over, and reference interval validation in accordance with CLSI guidelines.

Results: The within-laboratory CVs of the analytes tested in the study ranged between 1.00 and 7.84%, which met vendor claimed value in precision. In linearity test, most assays satisfied acceptable linearity criteria, best-fit first order regression or polynomial regression with nonlinearity smaller than ±10%, compared with linear regression. The recovery of each analyte distributed from 90.1 to 109.7%. The coefficient of determination (R) for each test was larger than 0.95 except for folate when compared to the results obtained from existing routine analyzer and statistically or clinically equivalent. The carry-over rates were acceptable, and reference intervals were validated.

Conclusion: Through this study, acceptable analytical performance of novel Alinity i system has been verified. It is expected to readily replace existing instrument and to be an option for laboratories considering introduction of automated immunoassay analyzer.
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http://dx.doi.org/10.1016/j.plabm.2020.e00185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652776PMC
November 2020

Thermoregulation of Biofilm Formation.

Appl Environ Microbiol 2020 10 28;86(22). Epub 2020 Oct 28.

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, South Korea

We investigated the effect of temperature on the biofilm formation of and revealed that the biofilm formation increased rapidly at temperatures lower than 25°C. formed the most robust biofilm of a conspicuous mushroom-like structure at 20°C. However, when the temperature increased to 25°C, the biofilm formation rapidly decreased. Above 25°C, as the temperature rose, the biofilm formation increased again little by little despite its less-structured form, indicating that 25°C is the low point of biofilm formation. The intracellular 3',5'-cyclic diguanylate (c-di-GMP) levels also decreased rapidly as the temperature rose from 20 to 25°C. The expression levels of , , and encoding Pel, alginate, and Psl, respectively, were also dramatically affected by temperature, with being regulated in a pattern similar to that of the intracellular c-di-GMP levels, and the pattern seen for regulation was the most similar to the actual biofilm formation pattern. Total exopolysaccharide production was thermoregulated and followed the regulation pattern of c-di-GMP. Interestingly, the thermoregulation patterns in biofilm formation were different depending on the strain of Unlike PAO1, another strain, PA14, showed a gradual decrease in biofilm formation and c-di-GMP in the range of 20 to 37°C, and clinical isolates also showed slightly different patterns in biofilm formation in conjunction with temperature change, suggesting that different strains may sense different temperature ranges for biofilm formation. However, it is obvious that forms more biofilms at lower temperatures and that temperature is an important factor in determining the biofilm formation. Biofilm formation is an important protection mechanism used by most microorganisms and provides cells with many advantages, like high infectivity, antibiotic resistance, and strong survivability. Since most persistent bacterial infections are believed to be associated with biofilms, biofilm control is an important issue in medicine, environmental engineering, and industry. Biofilm formation is influenced by various environmental factors. Temperature is the most direct environmental cue encountered by microorganisms. Here, we investigated the effect of temperature on the biofilm formation of , a notorious pathogen, and found that temperature is an important factor determining the amount and structure of biofilms. Low temperatures greatly increase biofilm formation and give biofilms a highly conspicuous structure. Although thermoregulation of biofilm formation is mainly mediated by c-di-GMP, some c-di-GMP-independent regulations were also observed. This study shows how biofilms are formed at various temperatures and provides new insights to control biofilms using temperature.
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http://dx.doi.org/10.1128/AEM.01584-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642082PMC
October 2020

The Effect of Wearing a Customized Mouthguard on Body Alignment and Balance Performance in Professional Basketball Players.

Int J Environ Res Public Health 2020 09 3;17(17). Epub 2020 Sep 3.

Department of Coaching, College of Physical Education, Kyung Hee University (Global Campus), 1732 Deokyoungdaero, Giheung-gu, Yongin-si, Gyeonggi-do 17014, Korea.

The present study examined the influence of a customized mouthguard on body alignment and balance performance in professional basketball players. Twenty-three professional male basketball players, aged 25.8 ± 8.6 years old, were voluntarily assigned to participate in three treatments, including no treatment (no mouthguard), acute treatment (wearing a mouthguard), and repeated treatments (8 weeks follow-up). Body alignment status, such as spinal and pelvic posture and balance performance, were measured at each time point using a 3D Formetric III (Germany) and a postural control device (Posturomed 202, Germany), respectively. A repeated MANOVA analysis with a Bonferroni post hoc test was applied, and the adjusted -value was set at 0.02. No significant treatment effect was observed in body alignment ( = 0.302). However, univariate analysis showed a significant difference in pelvic torsion, where it was decreased after acute and repeated mouthguard treatments compared to no treatment ( < 0.001). Kyphotic angle also increased significantly following 8 weeks of treatment compared to no treatment ( < 0.001) and acute treatment ( < 0.002). There was a significant treatment effect on balance performance ( < 0.001). Both static and dynamic balance performance improved following 8 weeks of treatment ( < 0.001). Our study revealed that a customized mouthguard provides a benefit to balance performance. Notably, repeated treatment impacts on balance performance more than acute treatment. Although our findings did not show a significant effect on body alignment, some positive results, such as pelvic torsion and kyphotic angle, may provide substantial information for developing future longitudinal studies with large sample sizes.
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http://dx.doi.org/10.3390/ijerph17176431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504132PMC
September 2020

High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence.

PLoS One 2020 26;15(8):e0238079. Epub 2020 Aug 26.

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Sitosterolemia is an inherited lipid disorder which presents with elevated serum sitosterol and can result in an increased risk of premature cardiovascular disease. However, sitosterol cannot be accurately measured by routine diagnostic assays, meaning that sitosterolemia diagnosis can often be difficult, especially with many clinical features overlapping with familial hypercholesterolemia. With such complications resulting in increasing reports of misdiagnosis, the prevalence of sitosterolemia is predicted to be much higher than previously reported.

Methods: Gas chromatography-mass spectrometry was utilized to measure sitosterol levels of normocholesterolemic and hypercholesterolemic children. Subsequently, an epidemiologically determined cutoff level of sitosterol was calculated and applied to estimate the prevalence of children with increased sitosterol and identify potential sitosterolemia patients. Massively parallel sequencing was used to confirm the diagnosis in suspected patients.

Results: Samples from 109 normocholesterolemic and 220 hypercholesterolemic were tested for phytosterols. Sitosterol and campesterol levels were significantly increased in hypercholesterolemic children (mean 22.0±45.9 μmol/L for sitosterol and 26.0±32.8 μmol/L for campesterol) compared to normocholesterolemic children (mean 12.1±4.9 μmol/L for sistosterol and 14.8±6.7 μmol/L for campesterol). Via application of a cutoff of 35.9 μmol/L, the prevalence rates for increased and overtly increased sitosterol in hypercholesterolemic children were 6.4% and 1.4% respectively. Furthermore, 3 suspected sitosterolemia patients were identified, with 2 patients receiving molecular confirmation for sitosterolemia diagnosis.

Conclusions: Our findings reaffirm that the prevalence of sitosterolemia is probably much higher than previously reported, which also indicates the significant risk of misdiagnosis of sitosterolemia with familial hypercholesterolemia. Special lipid testing including sitosterol, especially in children with uncontrolled hypercholesterolemia, is recommended in children in order to identify potential sitosterolemia patients that would otherwise be neglected.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238079PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449458PMC
October 2020

C5, A Cassaine Diterpenoid Amine, Induces Apoptosis via the Extrinsic Pathways in Human Lung Cancer Cells and Human Lymphoma Cells.

Int J Mol Sci 2020 Feb 14;21(4). Epub 2020 Feb 14.

Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea.

Apoptosis pathways in cells are classified into two pathways: the extrinsic pathway, mediated by binding of the ligand to a death receptor and the intrinsic pathway, mediated by mitochondria. Apoptosis is regulated by various proteins such as Bcl-2 (B-cell lymphoma 2) family and cellular FLICE (Fas-associated Death Domain Protein Interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), which have been reported to inhibit caspase-8 activity. In this study, it was found that C5 (3β-Acetyl-nor-erythrophlamide), a compound of cassaine diterpene amine from Erythrophleum fordii, induced cell apoptosis in a variety of types of cancer cells. Induction of apoptosis in cancer cells by C5 was inversely related to the level of Bcl-2 expression. Overexpression of Bcl-2 into cancer cells significantly decreased C5-induced apoptosis. It was also found that treatment of cancer cells with a caspase-8 inhibitor significantly suppressed C5-induced apoptosis; however, treatment with caspase-9 inhibitors did not affect C5-induced apoptosis, suggesting that C5 may induce apoptosis via the extrinsic pathway by activating caspase-8. It was confirmed that treatment with C5 alone induced an association of FADD with procaspase-8; however, overexpression of c-FLIP decreased C5-induced caspase-8 activation. In conclusion, C5 could be utilized as a new useful lead compound for the development of an anti-cancer agent that has the goal of apoptosis.
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http://dx.doi.org/10.3390/ijms21041298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072863PMC
February 2020

Effects of patient-specific mobility therapy for TMJ, neck, and shoulder dysfunction after submandibular gland tumor surgery: a case report.

Physiother Theory Pract 2020 Jan 9:1-6. Epub 2020 Jan 9.

Department of Physical Therapy, College of Health and Medical Science, Cheongju University, Cheongju, Republic of Korea.

 This case report describes a patient-specific mobility therapy (PSMT) program to restore range of motion (ROM) and overcome functional limitations of the temporomandibular joint (TMJ), neck, and shoulder in a 48-year-old man who underwent submandibular gland tumor surgery. The patient also received transcutaneous electrical stimulation and ultrasound to relieve pain. Treatment was provided four sessions per week for four weeks. The measured outcomes included the Neck Disability Index (NDI), Patient-Specific Functional Scale (PSFS), and mobility of the TMJ, neck, and shoulder. The ROM of the TMJ, neck, and shoulder improved from 4.00 mm to 21.00 mm, 1.67 cm to 6.40 cm, and 9.75° to 56.00°, respectively, during the 1 intervention phase when compared with the baseline phase, and these gains were also maintained in the later phases. Furthermore, the NDI and PSFS scores improved by 12.75 points (24.50 to 11.75) and 5.25 points (2.00 to 7.25), respectively. These findings demonstrate the success of PSMT in conjunction with transcutaneous electrical stimulation and ultrasound in alleviating pain and improving targeted impairments for this patient following submandibular gland tumor surgery.
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http://dx.doi.org/10.1080/09593985.2019.1710882DOI Listing
January 2020

Initial Evidence on the Impact of Performance-Based Treadmill Training on Pulmonary Function and Physical Performance in a Child with Bronchopulmonary Dysplasia: Single-Subject Experimental Study.

Phys Occup Ther Pediatr 2020 23;40(4):384-394. Epub 2019 Dec 23.

Department of Physical Therapy, College of Health and Medical Science, Cheongju University, Cheongju, Republic of Korea.

This study aimed to demonstrate the initial evidence on the impact of performance-based treadmill training on pulmonary function and physical performance of a patient with bronchopulmonary dysplasia (BPD). This study used a single-subject pre-experimental (A-B) research design (5 and 10 data points during the baseline and intervention phases, respectively) with a 4-month follow-up measurement. The subjects were a 5-year-old child diagnosed with bronchopulmonary dysplasia. Outcome measures were pulmonary function (forced vital capacity [FVC] and peak expiratory flow [PEF]) and physical performance (6-min walk test [6MWT], sit-to-stand test [STS], pediatric balance scale [PBS], and goal attainment scaling). Applying the 2 standard deviation method, the FVC, PEF, 6MWT, and STS test scores showed significant improvement compared to baseline values. In addition, the PBS and goal attainment scaling scores improved by 5.36% (42 points to 45 points) and 29.61% (37.6 points to 59.75 points) after the intervention, respectively. Gains were maintained at the 4-month follow-up. These findings suggest that performance-based treadmill training may be a possible treatment option to improve the pulmonary function and physical performance of children with BPD. Further rigorous studies are needed to establish evidence regarding the effectiveness of the training program among this population.
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http://dx.doi.org/10.1080/01942638.2019.1705455DOI Listing
January 2021

Quorum sensing-dependent post-secretional activation of extracellular proteases in .

J Biol Chem 2019 12 14;294(51):19635-19644. Epub 2019 Nov 14.

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, South Korea

secretes multiple proteases that are implicated in its pathogenesis, and most of them are regulated by quorum sensing (QS). In this study, we found that the activities of three major extracellular proteases, protease IV (PIV), elastase A (LasA), and elastase B (LasB), are reduced considerably when expressed in a QS mutant (MW1). PIV and LasA expressed in MW1 exhibited little activity, even when purified, and their activities were inhibited by noncleavage or binding of their propeptides. LasB was activated by a QS-dependent factor, indicating that, unlike what has been proposed previously, LasB is not autoactivated. When LasB was relieved from inhibition, it activated PIV, which then sequentially processed pro-LasA to mature LasA. When activated, LasB was not inhibited by exogenous addition of its propeptide, but LasA and PIV were inhibited by their propeptides, even after prior activation. These differences may be explained by the fact that LasB can degrade its own propeptide but PIV and LasA cannot. We also found that, although PIV is the preferred LasA-activating factor, LasB can also partially activate LasA. Overall, LasB, PIV, and LasA were activated postsecretionally in a cascading manner in which the initial activation of LasB was controlled tightly by QS at the protein level in addition to the well-known transcriptional control of these proteases by QS. Interestingly, human elastase also activated LasA, indicating that the activation cascade is triggered by host factors during infection. In summary, a QS-induced proteolytic cascade activates secreted proteases from
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http://dx.doi.org/10.1074/jbc.RA119.011047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926461PMC
December 2019

Effects of visual feedback training and visual targets on muscle activation, balancing, and walking ability in adults after hemiplegic stroke: a preliminary, randomized, controlled study.

Int J Rehabil Res 2020 Mar;43(1):76-81

Department of Physical Therapy, College of Health and Medical Science, Cheongju University, Cheongju City, Republic of Korea.

The aim of this randomized, controlled study was to investigate the effect of visual feedback through visual targets on muscle activity, balance, and gait in stroke patients. Patients were recruited from the inpatient unit of a rehabilitation hospital. Twenty-one patients who had experienced hemiplegic stroke were randomly assigned to two groups: an experimental group (visual feedback training with visual targets on gradual weight shifting), and a control group (visual feedback training on gradual weight shifting). All patients performed 30 minutes of comprehensive rehabilitation therapy followed by an additional 20 minutes of gradual weight shifting using visual feedback training with or without visual targets: three sets per day, five times a week, for 4 weeks. Significantly larger gains were identified in the experimental group compared to the control group due to gluteus medius muscle activation and the weight-bearing ability of the paretic side. Visual feedback training with visual targets during gradual weight bearing on the paretic side appears to improve the muscle activation and balancing abilities of hemiplegic stroke patients compared to visual feedback training alone.
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http://dx.doi.org/10.1097/MRR.0000000000000376DOI Listing
March 2020

Whole genome sequencing analysis of horse populations inhabiting the Korean Peninsula and Przewalski's horse.

Genes Genomics 2019 06 2;41(6):621-628. Epub 2019 Apr 2.

College of Animal Life Science, Kangwon National University, Chuncheon, 24341, Republic of Korea.

Background: The Jeju horse is an indigenous horse breed in Korea. However, there is a severe lack of genomic studies on Korean horse breeds.

Objective: The objective of this study was to report genomic characteristics of domestic horse populations that inhabit South Korea (Jeju, Jeju crossbred, and Thoroughbred) and a wild horse breed (Przewalski's horse).

Results: Using the equine reference genome assembly (EquCab 2.0), more than ~ 6.5 billion sequence reads were successfully mapped, which generated an average of 40.87-fold coverage throughout the genome. Using these data, we detected a total of 12.88 million SNPs, of which 73.7% were found to be novel. All the detected SNPs were deeply annotated to retrieve SNPs in gene regions using the RefSeq and Ensemble gene sets. Approximately 27% of the total SNPs were located within genes, whereas the remaining 73% were found in intergenic regions. Using 129,776 coding SNPs, we retrieved a total of 49,171 nonsynonymous SNPs in 12,351 genes. Furthermore, we identified a total of 10,770 deleterious nonsynonymous SNPs which are predicted to affect protein structure or function.

Conclusion: We showed numerous genomic variants from domestic and wild horse breeds. These results provide a valuable resource for further studies on functions of SNP-containing genes, and can aid in determining the molecular basis underlying variation in economically important traits of horses.
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http://dx.doi.org/10.1007/s13258-019-00795-wDOI Listing
June 2019

Perspectives towards antibiotic resistance: from molecules to population.

Authors:
Joon-Hee Lee

J Microbiol 2019 Mar;57(3):181-184

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.

For a long time, antibiotics have been 'magical weapons' to combat pathogenic microbes. The success of antibiotics is now greatly threatened by resistance to antibiotics and many scientists have already talked about the coming of the postantibiotic era. This special issue is prepared to understand recent research findings and new concepts about antibiotic resistance. Above all, this special issue explores mechanisms for the generation, selection, and spread of antibiotic resistance, and gives insight into what to target to prevent the development of antibiotic resistance. Just as antibiotics came from the concept of "magic bullet", a breakthrough will come from a new concept based on a profound understanding of antibiotic resistance.
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http://dx.doi.org/10.1007/s12275-019-0718-8DOI Listing
March 2019

Comparison of bupivacaine plus intrathecal fentanyl and bupivacaine alone for spinal anesthesia with intravenous dexmedetomidine sedation: a randomized, double-blind, noninferiority trial.

Reg Anesth Pain Med 2019 04 23;44(4):459-465. Epub 2019 Jan 23.

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

Background And Objectives: Fentanyl is widely used as an intrathecal adjuvant to local anesthetics to enhance the duration of spinal anesthesia. Recent evidence suggests that intravenous dexmedetomidine prolongs the duration of spinal anesthesia. This noninferiority study evaluated whether bupivacaine alone could provide a noninferior duration of block compared with bupivacaine and fentanyl when intravenous dexmedetomidine was administered intraoperatively.

Methods: Fifty-six patients scheduled for total knee arthroplasty under spinal anesthesia were randomly allocated to receive either bupivacaine 13 mg with intrathecal fentanyl 20 µg (Group BF) or bupivacaine 13 mg (Group B). Both groups underwent intravenous dexmedetomidine sedation throughout the surgery (1 µg kg for 10 min, followed by 0.5 µg kg h). The primary outcome was the time to two-segment regression of the sensory block. The noninferiority margin for the mean difference was predefined as -10 min. Secondary outcomes included postoperative pain scores, analgesics consumptions, and the incidences of pruritus, nausea, and vomiting.

Results: There was no significant difference in the two-segment regression time of sensory block (Group B 109.1±25.0 min vs Group BF 104.3±25.9 min; p=0.484). The mean difference in the two-segment regression time between the 2 groups was 4.8 min (95 % CI -8.9 to 18.6), demonstrating the noninferiority of bupivacaine alone. Secondary outcomes showed no significant differences between the two groups.

Conclusions: The duration of spinal anesthesia with bupivacaine alone is noninferior to that of bupivacaine plus fentanyl in patients receiving intravenous dexmedetomidine intraoperatively. Our results suggest that intrathecal fentanyl may not be required when intravenous dexmedetomidine is administered.

Trial Registration Number: NCT03105115.
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http://dx.doi.org/10.1136/rapm-2018-100084DOI Listing
April 2019

A Rho-Associated Coiled-Coil Containing Kinase Inhibitor, Y-27632, Improves Viability of Dissociated Single Cells, Efficiency of Colony Formation, and Cryopreservation in Porcine Pluripotent Stem Cells.

Cell Reprogram 2019 02 8;21(1):37-50. Epub 2019 Jan 8.

1 Department of Animal Bioscience, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju, Republic of Korea.

The establishment of porcine epiblast stem cells (pEpiSCs) and induced pluripotent stem cells (piPSCs) derived from diametrical derivations is of great importance in developing biomedical models. However, pEpiSCs and piPSCs have been technically much harder to culture than mouse embryonic stem cells, showing problematic properties such as spontaneous differentiation and apoptosis after cryopreservation. Therefore, we demonstrated that Y-27632 as a Rho-associated coiled-coil containing kinase inhibitor could prevent dissociated pEpiSCs and piPSCs from undesirable differentiation and apoptosis in cryopreservation protocols. pEpiSC 2, 8 lines, Sendai virus-induced pluripotent stem cells (Sev-iPSCs), and lentivirus-induced pluripotent stem cells were cultured with 10 μM Y-27632 before collecting dissociated cells retrieved from colonies using various enzymes. Dissociated single cells were transferred into freezing mediums (open pulled straw vitrification, STEM-CELLBANKER (SCB), 10% dimethylsulfoxide in serum) for cryopreservation. The rates of viability and colony formation obtained from dissociated porcine stem cells after freezing/thawing were examined in the presence of Y-27632. The characteristics of pluripotency and in vitro differentiation were also examined in these stem cells treated with Y-27632 after cryopreservation. As a result, the viability and efficiency of colony formation of dissociated pEpiSCs (2, 8 lines) and Sev-iPSCs treated with 10 μM Y-27632 using the SCB cryopreservation protocol were significantly increased when compared with those of nontreated Y-27632 (p < 0.05). Pluripotency genes (OCT-3/4, NANOG, and SOX2) were positively expressed in Y-27632-treated porcine pluripotent stem cells. Also, in vitro differentiation of these stem cells was successfully induced in the presence of 10 μM Y-27632. These results indicated that treatment of Y-27632 for single-cell dissociation and the SCB cryopreservation protocol could facilitate handling porcine pluripotent stem cells and provide the widespread use of these stem cells.
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http://dx.doi.org/10.1089/cell.2018.0020DOI Listing
February 2019

Antibiofilm effect of biofilm-dispersing agents on clinical isolates of Pseudomonas aeruginosa with various biofilm structures.

J Microbiol 2018 Dec 25;56(12):902-909. Epub 2018 Oct 25.

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.

Pseudomonas aeruginosa, an opportunistic human pathogen, causes many biofilm-mediated chronic infections. In this study, biofilm structures of various clinical strains of P. aeruginosa isolated from hospitalized patients were examined and their influence on the biofilm-dispersing effects of chemicals was investigated. The clinical isolates formed structurally distinct biofilms that could be classified into three different groups: 1) mushroom-like, 2) thin flat, and 3) thick flat structures. A dispersion of these differently structured biofilms was induced using two biofilm-dispersing agents, anthranilate and sodium nitroprusside (SNP). Although both SNP and anthranilate could disperse all types of biofilms, the thick flat biofilms were dispersed less efficiently than the biofilms of other structures. This suggests that biofilm-dispersing agents have higher potency on the biofilms of porous structures than on densely packed biofilms.
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http://dx.doi.org/10.1007/s12275-018-8336-4DOI Listing
December 2018

Lumbosacral and thoracolumbosacral cerebrospinal fluid volume changes in neonates, infants, children, and adolescents: A retrospective magnetic resonance imaging study.

Paediatr Anaesth 2019 01 23;29(1):92-97. Epub 2018 Nov 23.

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

Background: The volume of cerebrospinal fluid can affect the pharmacokinetics and pharmacodynamics of local anesthetics for spinal anesthesia and other intrathecal medications.

Aims: The objective of this study was to estimate the lumbosacral cerebrospinal fluid volume and thoracolumbosacral cerebrospinal fluid volume using magnetic resonance images in pediatric patients from neonates and infants to adolescents.

Methods: Spinal magnetic resonance images of 500 pediatric patients (age <18 years) were reviewed. The lumbosacral cerebrospinal fluid volumes of 418 patients and thoracolumbosacral cerebrospinal fluid volumes of 248 patients were measured. The relationship between cerebrospinal fluid volumes and age, height, and weight were evaluated. The lumbosacral and thoracolumbosacral cerebrospinal fluid volumes per weight were calculated to elucidate developmental changes.

Results: The lumbosacral and thoracolumbosacral cerebrospinal fluid volumes showed linear correlations with height (r = 0.730 and r = 0.661, respectively), whereas they showed curvilinear correlations with age (r = 0.752 and r = 0.717, respectively) and weight (r = 0.734 and r = 0.734, respectively). The mean lumbosacral cerebrospinal fluid volume per weight (mL/kg) was 0.85 (standard deviation [SD]: 0.19, 95% confidence interval [CI]: 0.81-0.90) in neonates and infants, 0.86 (SD: 0.22, 95% CI: 0.83-0.89) in toddlers and preschoolers, 0.71 (SD: 0.26, 95% CI: 0.66-0.76) in schoolers, and 0.54 (SD: 0.20, 95% CI: 0.49-0.60) in adolescents. The mean thoracolumbosacral cerebrospinal fluid volume per weight (mL/kg) was 1.95 (SD: 0.37, 95% CI: 1.86-2.04) in neonates and infants, 1.82 (SD: 0.41, 95% CI: 1.75-1.88) in toddlers and preschoolers, 1.38 (SD: 0.40, 95% CI: 1.23-1.52) in schoolers, and 0.99 (SD: 0.34, 95% CI: 0.45-1.53) in adolescents.

Conclusion: The lumbosacral and thoracolumbosacral cerebrospinal fluid volumes in pediatric patients were much smaller than previously presented values, showing linear correlations with height, and demonstrate curvilinear correlations with age and weight.
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http://dx.doi.org/10.1111/pan.13530DOI Listing
January 2019

Predicting the Depth of the Lumbar Plexus in Pediatric Patients: A Retrospective Magnetic Resonance Imaging Study.

Anesth Analg 2020 01;130(1):201-208

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

Background: The lumbar plexus (LP) block is commonly used for analgesia for lower extremities. If the depth of the LP (LPD) can be predicted, the performance time and procedure-related complications could be reduced.

Methods: Three hundred sixty-one magnetic resonance images of pediatric patients (<18 years of age) were analyzed. Simple linear regression and multiple linear regression analyses were performed to predict the LPD using patient age, weight, height, and the distance between the midline and posterior superior iliac spine (midline-PSIS). The ratio of the distance between the midline and the most lateral aspect of the LP (midline-LP) to midline-PSIS (midline-LP/midline-PSIS ratio) was calculated to suggest a needle insertion point at the L4/L5 intervertebral level. The presence of the kidney at the L4 level and the L4/L5 intervertebral level was determined.

Results: The LPD at the L4/L5 intervertebral levels was predicted using the equation LPD = 0.844 × weight (kg) + 25.8 (mm) in pediatric patients <18 years of age (r = 0.791; 95% confidence interval [CI] of r, 0.753-0.829). The overall midline-LP/midline-PSIS ratio was 0.87 (95% CI, 0.86-0.89), and the ratio was higher in neonates and infants (0.98 [95% CI, 0.95-1.02]) than in the other age groups. The presence of the lower kidney pole at the L4 level was common in pediatric patients (43.7% of neonates and infants and 13.7% of toddlers and preschool-aged children). The lower kidney pole was observed at the L4/L5 level in 6 patients (1.7%).

Conclusions: When LP block is performed in pediatric patients, the LPD and risk of renal injury should be considered for successful and safe analgesic block.
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http://dx.doi.org/10.1213/ANE.0000000000003836DOI Listing
January 2020

Bacterial ornithine lipid, a surrogate membrane lipid under phosphate-limiting conditions, plays important roles in bacterial persistence and interaction with host.

Environ Microbiol 2018 11 28;20(11):3992-4008. Epub 2018 Oct 28.

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, 609-735, South Korea.

Ornithine lipids (OLs) are bacteria-specific lipids that are found in the outer membrane of Gram (-) bacteria and increase as surrogates of phospholipids under phosphate-limited environmental conditions. We investigated the effects of OL increase in bacterial membranes on pathogen virulence and the host immune response. In Pseudomonas aeruginosa, we increased OL levels in membranes by overexpressing the OL-synthesizing operon (olsBA). These increases changed the bacterial surface charge and hydrophobicity, which reduced bacterial susceptibility to antibiotics and antimicrobial peptides (AMPs), interfered with the binding of macrophages to bacterial cells and enhanced bacterial biofilm formation. When grown under low phosphate conditions, P. aeruginosa became more persistent in the treatment of antibiotics and AMPs in an olsBA-dependent manner. While OLs increased persistence, they attenuated P. aeruginosa virulence; in host cells, they reduced the production of inflammatory factors (iNOS, COX-2, PGE and nitric oxide) and increased intracellular Ca release. Exogenously added OL had similar effects on P. aeruginosa and host cells. Our results suggest that bacterial OL plays important roles in bacteria-host interaction in a way that enhances bacterial persistence and develops chronic adaptation to infection.
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http://dx.doi.org/10.1111/1462-2920.14430DOI Listing
November 2018

Effects of Circuit Training According to the Feedback Type on Psychological and Physical Health of Workers with Social Anxiety Disorder.

Iran J Public Health 2018 Jul;47(Suppl 1):65-73

Dept. of Sports Coaching, College of Physical Education, Kyung-hee University, Yongin, Korea.

Background: The effects of circuit training was investigated according to the feedback type on the psychological (social anxiety, anxiety, positive emotion) health and physical (body composition, physical fitness) health of social anxiety disorder workers.

Methods: Sixty male workers in H Company in Seoul, South Korea with social anxiety disorder were divided into four groups (positive, negative, mixed, no feedback) by conducting a circuit training program in sport center of H company during 3 times per week, total 8 weeks from Feb 1st to Mar 31st, 2017. The results of the pre-test and post-test were analyzed as follows.

Results: 1) In effect of social anxiety, there were significant differences in the positive, negative, and mixed feedback groups. 2) In the effect of anxiety, there were significant differences in the positive, negative, and mixed feedback groups. 3) In the effect of positive emotion, there were significant differences in the positive, negative, mixed, and no feedback groups. 4) In the effect of body composition, body fat mass and body fat percentage have significant differences in the positive, negative, mixed, and no feedback groups. And fat free mass has significant differences in the positive and mixed feedback groups. 5) In the effect of physical fitness, grip strength, wall squat, bending forward have significant differences in positive, negative, mixed, and no feedback groups.

Conclusion: The circuit training program improves the social anxiety disorder and positively affects the psychological health and physical health of participants. To participate in continuous exercise, personal training should be accompanied by the correct feedback of the leader.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124146PMC
July 2018

Genome-wide analysis of Hanwoo and Chikso populations using the BovineSNP50 genotyping array.

Genes Genomics 2018 12 30;40(12):1373-1382. Epub 2018 Aug 30.

College of Animal Life Science, Kangwon National University, Chuncheon, 24341, Republic of Korea.

Hanwoo and Chikso are classified as Korean native cattle breeds that are currently registered with the Food and Agriculture Organization. However, there is still a lack of genomic studies to compare Hanwoo to Chikso populations. The objective of this study was to perform genome-wide analysis of Hanwoo and Chikso populations, investigating the genetic relationships between these two populations. We genotyped a total of 319 cattle including 214 Hanwoo and 105 Chikso sampled from Gangwon Province Livestock Technology Research Institute, using the Illumina Bovine SNP50K Beadchip. After performing quality control on the initially generated datasets, we assessed linkage disequilibrium patterns for all the possible SNP pairs within 1 Mb apart. Overall, average r values in Hanwoo (0.048) were lower than Chikso (0.074) population. The genetic relationship between the populations was further assured by the principal component analysis, exhibiting clear clusters in each of the Hanwoo and Chikso populations, respectively. Overall heterozygosity for Hanwoo (0.359) was slightly higher than Chikso (0.345) and inbreeding coefficient was also a bit higher in Hanwoo (- 0.015) than Chikso (- 0.035). The average F value was 0.036 between Hanwoo and Chikso, indicating little genetic differentiation between those two breeds. Furthermore, we found potential selection signatures including LRP1B and NTRK2 genes that might be implicated with meat and reproductive traits in cattle. In this study, the results showed that both Hanwoo and Chikso populations were not under severe level of inbreeding. Although the principal component analysis exhibited clear clusters in each of the populations, we did not see any clear evidence that those two populations are highly differentiated each other.
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http://dx.doi.org/10.1007/s13258-018-0733-xDOI Listing
December 2018

Erratum: Effects of exercise training on stroke risk factors, homocysteine concentration, and cognitive function according the genotype in stroke patients.

J Exerc Rehabil 2018 06 30;14(3):536. Epub 2018 Jun 30.

Department of Prescription & Rehabilitation of Exercise, College of Physical Exercise, and Department of Kinesiologic Medical Science, Graduate School Dankook University, Cheonan, Korea.

[This corrects the article on p. 267 in vol. 14, PMID: 29740562.].
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http://dx.doi.org/10.12965/jer.18corri.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028225PMC
June 2018

Effects of exercise training on stroke risk factors, homocysteine concentration, and cognitive function according the genotype in stroke patients.

J Exerc Rehabil 2018 04 26;14(2):267-274. Epub 2018 Apr 26.

Department of Prescription & Rehabilitation of Exercise, College of Physical Exercise, and Department of Kinesiologic Medical Science, Graduate School Dankook University, Cheonan, Korea.

The apolipoprotein E () gene has been suggested to be associated with stroke and dementia. However, the effects of exercise training on dementia according to the genotype are not consistent to those reported by previous studies. Therefore, we examined the effects of exercise training on stroke risk factors including blood pressure, lipid profiles, homocysteine (Hcy) concentrations, and cognitive function according to the genotype in stroke patients. We examined the stroke risk factors, Hcy, and cognitive function in 28 ischemic stroke patients before and after 6 months of exercise training. After exercise training, body weight, body mass index (BMI), and percent body fat decreased significantly in both APOE groups. According to the genotype, the changes in BMI in the APOE ɛ4 group higher than those in APOE ɛ3 group significantly. Total cholesterol (TC), low-density lipoprotein (LDL)-C, triglyceride (TG), and Hcy decreased and high-density lipoprotein (HDL)-C increased significantly in the both groups. According to the genotype, systolic blood pressure in the APOE ɛ4 group decreased, but in the APOE ɛ3 group increased after exercise training. TC, LDL-C, and TG in the APOE ɛ4 group decreased more extensively than those in the APOE ɛ3 group after exercise training. VO (maximal oxygen consumption) and cognition increased significantly in both groups. Folate acid intake also increased significantly in both groups. The genotype affects variations in the risk factors of stroke after exercise training. However, the Hcy and cognitive function did not differ based on the genotype.
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http://dx.doi.org/10.12965/jer.1836108.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931164PMC
April 2018

Evaluation of the fit of zirconia copings fabricated by direct and indirect digital scanning procedures.

J Prosthet Dent 2018 Aug 7;120(2):225-231. Epub 2018 Feb 7.

Professor, Department of Prosthodontics, Yonsei University College of Dentistry, Seoul, Republic of Korea. Electronic address:

Statement Of Problem: Intraoral scanners are effective for direct digital scans when dental restorations are fabricated using computer-aided design and computer-aided manufacturing (CAD-CAM); however, if the abutment tooth cannot be dried completely or the prepared margin is placed subgingivally, accurate digital images cannot always be guaranteed.

Purpose: The purpose of this in vitro study was to compare the internal and marginal discrepancies of zirconia copings fabricated directly using an intraoral scanner with those fabricated indirectly with impression scanning.

Material And Methods: Forty-five resin dies fabricated with a 3-dimensional (3D) printer were divided into 3 groups: direct scanning (DS), impression scanning (IMP), and lost-wax casting (LW). For the DS group, a resin die was scanned with an intraoral scanner (Trios; 3Shape), whereas for the IMP group, impressions made with polyether were scanned with a cast scanner (D700; 3Shape). The zirconia copings were fabricated in the same way in the DS and IMP groups. For the LW group, impressions were made in the same way as in the IMP group, and Ni-Cr alloy copings were fabricated using LW. The marginal and internal discrepancies of the copings were measured by cementing them onto resin dies, embedding them in acrylic resin, and sectioning them in a buccolingual direction. The cement layer was measured, and the Kruskal-Wallis test was used to detect significant differences (α=.05). A nonparametric Friedman test was also performed to compare the measurements of each group by location (α=.05).

Results: The mean marginal discrepancies in the DS, IMP, and LW groups were 18.1 ±9.8, 23.2 ±17.2, and 32.3 ±18.6 μm (mean ±standard deviation), respectively. The mean internal discrepancies of the DS, IMP, and LW groups in the axial area were 38.0 ±9.1, 47.0 ±16.3, and 36.5 ±15.8 μm, and those in the occlusal area were 36.7 ±16.9, 33.4 ±21.6, and 44.5 ±31.9 μm, respectively. No statistically significant differences were found in marginal or internal discrepancies among groups (P>.05).

Conclusions: Within the limitations of this study, the zirconia copings fabricated with CAD-CAM using different digitization methods and Ni-Cr copings fabricated using the lost-wax technique and casting produced clinically acceptable marginal and internal discrepancies. No significant differences were found among the DS, IMP, and LW groups.
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http://dx.doi.org/10.1016/j.prosdent.2017.08.003DOI Listing
August 2018

Idiopathic hypereosinophilia is clonal disorder? Clonality identified by targeted sequencing.

PLoS One 2017 31;12(10):e0185602. Epub 2017 Oct 31.

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×103/μL, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosinophilopoietic pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185602PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663336PMC
November 2017

Antibacterial activities of viriditoxin congeners and synthetic analogues against fish pathogens.

Bioorg Med Chem Lett 2017 11 9;27(22):4970-4974. Epub 2017 Oct 9.

College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address:

Viriditoxin is a fungal secondary metabolite of the fungus Paecilomyces variotii derived from the inner tissues of the giant jellyfish Nemopilema nomurai. Viriditoxin exhibits antibacterial activity against Streptococcus iniae and Streptococcus parauberis, which are major pathogens of aqua cultured fish. Viriditoxin induced abnormal cell morphologies in the fish pathogens S. iniae and S. parauberis, presumably by inhibiting FtsZ polymerization as was previously observed in Escherichia coli. Synthetic analogues of viriditoxin, designed based on docking simulation results to FtsZ of Staphylococcus aureus, were prepared and compared with viriditoxin for antibacterial activity. Reconstitution of free hydroxyl or carboxyl groups of the methoxyl or methyl ester groups of viriditoxin led to significant reduction of antibacterial activity, implying that the natural molecule is optimized for antibacterial activity to deter bacteria potentially harmful to Paecilomyces.
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http://dx.doi.org/10.1016/j.bmcl.2017.10.015DOI Listing
November 2017