Publications by authors named "Soo Hyun Kim"

598 Publications

Enhanced Regeneration of Vascularized Adipose Tissue with Dual 3D-Printed Elastic Polymer/dECM Hydrogel Complex.

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea.

A flexible and bioactive scaffold for adipose tissue engineering was fabricated and evaluated by dual nozzle three-dimensional printing. A highly elastic poly (L-lactide-co-ε-caprolactone) (PLCL) copolymer, which acted as the main scaffolding, and human adipose tissue derived decellularized extracellular matrix (dECM) hydrogels were used as the printing inks to form the scaffolds. To prepare the three-dimensional (3D) scaffolds, the PLCL co-polymer was printed with a hot melting extruder system while retaining its physical character, similar to adipose tissue, which is beneficial for regeneration. Moreover, to promote adipogenic differentiation and angiogenesis, adipose tissue-derived dECM was used. To optimize the printability of the hydrogel inks, a mixture of collagen type I and dECM hydrogels was used. Furthermore, we examined the adipose tissue formation and angiogenesis of the PLCL/dECM complex scaffold. From in vivo experiments, it was observed that the matured adipose-like tissue structures were abundant, and the number of matured capillaries was remarkably higher in the hydrogel-PLCL group than in the PLCL-only group. Moreover, a higher expression of M2 macrophages, which are known to be involved in the remodeling and regeneration of tissues, was detected in the hydrogel-PLCL group by immunofluorescence analysis. Based on these results, we suggest that our PLCL/dECM fabricated by a dual 3D printing system will be useful for the treatment of large volume fat tissue regeneration.
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http://dx.doi.org/10.3390/ijms22062886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999751PMC
March 2021

Relationships Between Oral-Mucosal Pressure Ulcers, Mechanical Conditions, and Individual Susceptibility in Intubated Patients Under Intensive Care: A PCR-Based Observational Study.

Biol Res Nurs 2021 Mar 11:1099800421998071. Epub 2021 Mar 11.

Department of Nursing, College of Natural Science, Pukyong National University, Busan, South Korea.

Purpose: This study was performed to determine the relationship between oral-mucosal pressure ulcer (PU) stage and mechanical conditions and individual susceptibility in intubated patients.

Methods: We collected 80 patient-days data from an intensive care unit of a 700-bed hospital in Korea. We analyzed oral-mucosal PUs, medical records, amount of saliva, and oral mucosal swabs. Bacterial abundance was enumerated by real-time polymerase chain reaction. The χ or Fisher's exact test, t-test or Mann-Whitney U test, and Spearman's rho correlation analysis were performed.

Results: The incidence of overall oral-mucosal PUs was 31.3%, and in the maxillary and mandibular sites were 16.3% and 26.3%, respectively. There were significant correlations between the maxillary site PU stage and restraint use (r = .43, < .001), albumin level (r = -.22, = .046), and relative abundance of (r = .45, < .001) and (r = -.24, = .033). In the mandibular sites, there were significant correlations between PU stage and restraint use (r = .30, = .008), level of consciousness (r = .31, .005), and relative abundance of (r = .25, .028) and (r = .22, p = .046).

Conclusions: Frequent monitoring and repositioning the mechanical pressure on the oral-mucosa could be an effective preventive strategy against the development and advancement of oral-mucosal PUs. Additionally, monitoring the oral microorganisms can prevent advanced stage oral-mucosal PUs in intubated patients.
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http://dx.doi.org/10.1177/1099800421998071DOI Listing
March 2021

Supportive Care Needs and Health-Related Quality of Life of Esophageal Cancer Survivors.

Asia Pac J Oncol Nurs 2021 Mar-Apr;8(2):164-171. Epub 2021 Jan 29.

School of Nursing, University of Texas at Austin, Austin, TX, USA.

Objective: The aim of this study is (1) to describe the prevalence and correlates of unmet needs among esophageal cancer survivors (ECS) in Korea and (2) to identify the association between unmet needs and health-related quality of life (HRQOL).

Methods: We used a cross-sectional descriptive study design. Participants were 118 ECS from a hospital in Korea who received surgery at least 12 months before participating. We collected data including the Supportive Care Needs Survey-short form 34 and to measure HRQOL, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 with a self-report questionnaire.

Results: Participants' mean age was 65.2 years, and 92.4% were male. Among five domains of supportive care needs, unmet need prevalence ranged from 0.8% to 50%. The most commonly reported domains of unmet needs were Health System and Information and Physical and Daily Living. Participants with unmet needs in Psychological Needs, Physical and Daily Living Needs, and Patient Care and Support Needs demonstrated significantly poorer HRQOL in almost all measured domains.

Conclusions: Our finding suggests that Korean ECS had substantial unmet needs, especially in the Health System and Information domain. Psychological, Patient Care and Support, and Physical and Daily Living Needs were related to HRQOL. The study can advance understanding of priority issues in ECS.
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http://dx.doi.org/10.4103/apjon.apjon_60_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934594PMC
January 2021

Kidney Mesenchymal Stem Cell-derived Extracellular Vesicles Engineered to Express Erythropoietin Improve Renal Anemia in Mice with Chronic Kidney Disease.

Stem Cell Rev Rep 2021 Mar 2. Epub 2021 Mar 2.

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, the Republic of Korea.

Extracellular vesicles (EVs) shed from kidney mesenchymal stem cells (KMSCs) show protective effects against acute kidney injury and progressive kidney fibrosis via mRNA transfer. Previous studies report improvement of renal anemia following administration of genetically modified MSCs or peritoneal mesothelial cells that secrete erythropoietin (EPO). Here, we determined whether EPO-secreting KMSC-derived EVs (EPO-EVs) can improve renal anemia in mouse models of chronic kidney disease (CKD). The mouse CKD and renal anemia model was induced by electrocoagulation of the right renal cortex and sequential left nephrectomy. At six weeks post-nephrectomy, we observed significantly lower hemoglobin (10.4 ± 0.2 vs. 13.2 ± 0.2 g/dL) and significantly higher blood urea nitrogen and serum creatinine levels in CKD mice relative to controls (60.5 ± 0.5 and 0.37 ± 0.09 mg/dL vs. 19.9 ± 0.5 and 0.12 ± 0.02 mg/dL, respectively). Genetically engineered EPO-KMSCs secreted 71 IU/mL EPO/10 cells/24 h in vitro, and EPO-EVs isolated by differential ultracentrifugation expressed EPO mRNA and horizontally transferred EPO mRNA into target cells in vitro and in vivo. Furthermore, at two weeks post-injection of EPO-KMSCs or EPO-EVs into CKD mice with renal anemia, we observed significant increases in hemoglobin levels (11.7 ± 0.2 and 11.5 ± 0.2 vs. 10.1 ± 0.2 g/dL, respectively) and significantly lower serum creatinine levels at eight weeks in comparison to mice receiving vehicle control (0.30 ± 0.00 and 0.23 ± 0.03 vs. 0.43 ± 0.06 mg/dL, respectively). These results demonstrate that intraperitoneal administration of EPO-EVs significantly increased hemoglobin levels and renal function in CKD mice, suggesting the efficacy of these genetically engineered EVs as a promising novel strategy for the treatment of renal anemia.
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http://dx.doi.org/10.1007/s12015-021-10141-xDOI Listing
March 2021

Change of right ventricular systolic pressure can indicate dasatinib-induced pulmonary arterial hypertension in chronic myeloid leukemia.

Cancer Med 2021 Mar 15;10(5):1515-1524. Epub 2021 Feb 15.

Department of Hematology, Catholic Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Background: We investigated the feasibility of the clinical application of non-invasive transthoracic echocardiography for diagnosis of pulmonary arterial hypertension induced by dasatinib (D-PAH) in chronic myeloid leukemia (CML).

Methods: A total of 451 CML patients who were examined by 2D-echocardiography at least once at baseline and/or during dasatinib therapy as frontline (n = 196) and subsequent line (n = 255) therapies were included in this study. D-PAH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg with relevant symptoms and the absence of other specific etiologies.

Results: A total of 847 echocardiographies were performed including at baseline (n = 255) and during dasatinib treatment (n = 592). During the median of 36.2 (0.1-181.8) months of dasatinib therapy, the level of RVSP gradually increased (Spearman's r = 0.2819, p < 0.001) and the mean RVSP was significantly increased after taking dasatinib therapy compared with baseline. During dasatinib therapy, 56 (12.4%) patients had RVSP >40 mm Hg without (asymptomatic, n = 27, 48.2%) or with symptoms (D-PAH, n = 29, 51.8%). All asymptomatic patients maintained dasatinib therapy without further symptoms and the D-PAH patients ultimately switched to other tyrosine kinase inhibitors. After dasatinib discontinuation, 13 (45%) and 15 (52%) patients showed RVSP normalization and gradual decrease, respectively.

Conclusions: Our large cohort study demonstrated that the gradual increment of RVSP might be induced by dasatinib and non-invasive echocardiography can be fast way for early diagnosis as well as for monitoring of D-PAH.
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http://dx.doi.org/10.1002/cam4.3588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940235PMC
March 2021

Which Out-of-Hospital Cardiac Arrest Patients without ST-Segment Elevation Benefit from Early Coronary Angiography? Results from the Korean Hypothermia Network Prospective Registry.

J Clin Med 2021 Jan 23;10(3). Epub 2021 Jan 23.

Department of Emergency Medicine, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

The effect of early coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation (STE) is still controversial. It is not known which subgroups of patients without STE are the most likely to benefit. The objective of this study was to evaluate the association between emergency CAG and neurologic outcomes and identify subgroups with improved outcomes when emergency CAG was performed. This prospective, multicenter, observational cohort study was based on data from the Korean Hypothermia Network prospective registry (KORHN-PRO) 1.0. Adult OHCA patients who were treated with targeted temperature management (TTM) without any obvious extracardiac cause were included. Patients were dichotomized into early CAG (≤24 h) and no early CAG (>24 h or not performed) groups. High-risk patients were defined as having the Global Registry of Acute Coronary Events (GRACE) score > 140, time from collapse to return of spontaneous circulation (ROSC) > 30 min, lactate level > 7.0 mmol/L, arterial pH < 7.2, cardiac enzyme elevation and ST deviation. The primary outcome was good neurologic outcome at 6 months after OHCA. Of the 1373 patients from the KORHN-PRO 1.0 database, 678 patients met the inclusion criteria. The early CAG group showed better neurologic outcomes at 6 months after cardiac arrest (CA) (adjusted odds ratio: 2.21 (1.27-3.87), = 0.005). This was maintained even after propensity score matching (adjusted odds ratio: 2.23 (1.39-3.58), < 0.001). In the subgroup analysis, high-risk patients showed a greater benefit from early CAG. In contrast, no significant association was found in low-risk patients. Early CAG was associated with good neurologic outcome at 6 months after CA and should be considered in high-risk patients.
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http://dx.doi.org/10.3390/jcm10030439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865270PMC
January 2021

Development of an Anisotropically Organized Brain dECM Hydrogel-Based 3D Neuronal Culture Platform for Recapitulating the Brain Microenvironment in Vivo.

ACS Biomater Sci Eng 2020 01 31;6(1):610-620. Epub 2019 Dec 31.

School of Electrical and Electronic Engineering, Yonsei University, Seoul 03722, Republic of Korea.

To mimic the brain tissue microenvironment in vitro, the biological and structural properties of the utilized system must be similar to those of the native brain in the microenvironment in vivo. To promote the bioactive (biological) properties of matrix hydrogels, we used the decellularized extracellular matrix (dECM) of porcine brain, which was found to enhance neuronal differentiation/outgrowth and neuron-to-brain dECM interactions. To implement the desired structural properties, we aligned microfibrils within a composite hydrogel mixed with the brain dECM and collagen I, with or without encapsulated neurons, by the stretching and releasing of a hydrogel-based chip. We then tested the ability of the aligned brain dECM hydrogel-based three-dimensional (3D) culture platform to mimic the in vivo brain microenvironment. We found that dECM-containing gels harbored brain-derived ECM proteins, including collagen I, collagen IV, laminin, and various cytokines, and that neurons incubated in these gels exhibited enhanced neurite outgrowth and development compared to those incubated in collagen gel (dECM 0 mg/mL). We evaluated the surface morphology and mechanical properties of the hydrogel with and without the brain dECM and found that their encapsulated neurons showed similar levels of cell viability. We then used a mechanical process to align the composite dECM hydrogel, conferring the desired structural properties to our system. Together, our results suggest that our newly developed brain dECM-based 3D culture platform could potentially be further developed for use in drug screening.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01512DOI Listing
January 2020

The association between L1 skeletal muscle index derived from routine CT and in-hospital mortality in CAP patients in the ED.

Am J Emerg Med 2021 04 26;42:49-54. Epub 2020 Dec 26.

Department of Emergency Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Introduction: Low muscle mass is associated with an increased mortality risk due to medical comorbidities such as chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease. Computed tomography (CT) has been identified as the gold standard for measuring body composition. We evaluated the relationship between the L1 SMI measured from CT and in-hospital mortality in patients with community-acquired pneumonia (CAP).

Methods: From January 2015 to June 2015, 311 patients who were diagnosed with CAP and underwent CT in the ED were retrospectively analyzed. Multivariate binary logistic regression analysis was used to assess independent predictors of in-hospital mortality. All variables with a significance level < 0.1 by univariate analysis were included in a multivariate logistic regression model. The primary outcome was all-cause in-hospital mortality.

Results: Among the 311 patients, 33 (10.6%) died. We divided the patients into two groups based on the optimal sex-specific cut-off value of the L1 SMI (45 cm/m in males and 40 cm/m in females). A low L1 SMI was present in 90 (28.9%) of the 311 patients. In multivariate analysis, low L1 SMI, diabetes mellitus, albumin and APACHE II score were significantly associated with in-hospital mortality (aOR 3.39, 3.73, 0.09 and 1.10, respectively).

Conclusion: SMI assessment at L1 is achievable in patients with CAP receiving routine chest CT, and the L1 SMI is associated with high in-hospital mortality, more hospitalizations and ventilator application in patients with CAP in the ED. This could help establish an early strategy for critical care of patients with L1 SMI obtained by chest CT for diagnosis in CAP patients in the ED.
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http://dx.doi.org/10.1016/j.ajem.2020.12.064DOI Listing
April 2021

Femoral matched tibia component rotation has little effect on the tibial torsion after total knee arthroplasty.

Knee Surg Sports Traumatol Arthrosc 2021 Jan 15. Epub 2021 Jan 15.

Department of Orthopedic Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul, 08308, Republic of Korea.

Purpose: Tibiofemoral synchronization technique matches the rotational alignment of the tibial component to the femoral component during the total knee arthroplasty (TKA). The rotational axis of the proximal tibia can be changed by this technique, which affects tibial torsion postoperatively. The purpose of this study was to investigate whether the tibiofemoral synchronization technique affect the tibial torsion, and the lower limb rotation after primary TKA. It was hypothesised that the tibial torsion would change after primary TKA.

Methods: Ninety-three posterior stabilised TKAs from 89 patients were included from January 2017 to December 2018. Mechanical hip-knee-ankle axis (mHKA), in plain radiographs, femoral anteversion, tibial torsion, femoral neck-malleolar angle (FNMA), and rotational alignment of the femoral and the tibial components in pre- and postoperative CT scans were measured by two blinded observers. The primary outcome was a postoperative change in femoral anteversion, tibial torsion and FNMA. Clinical outcomes were evaluated using the American Knee Society Knee Score (AKSKS)/Function Score (AKSFS), and Oxford Knee Score (OKS) preoperatively and at 1 year after TKA. Patients' perception of changes in the foot progression angle after TKA was investigated. Statistical significance was set at p < 0.05.

Results: The mean rotational mismatch between the femoral and the tibial component was 0.6 ± 3.2°. There was a significant decrease in femoral anteversion (9.5 ± 6.7° vs. 5.2 ± 6.6°, p < 0.001), and a significant increase in the FNMA (17.6 ± 9.7° vs. 21.8 ± 10.5°, p = 0.005) after TKA, while no significant change in tibia torsion was observed (25.4 ± 8.8° vs. 24.9 ± 9.3°, p = 0.739). AKSS (37.8 ± 15.1 vs. 92.8 ± 8.8, p < 0.001), AKSFS (53.9 ± 18.1 vs. 89.9 ± 5.3, p < 0.001), and OKS (18.0 ± 7.3 vs. 39.9 ± 4.8, p < 0.001) were significantly improved at 1 year after TKA. Ten knees (11%) had changes in tibial torsion greater than ± 10° postoperatively. Four of five patients who had changes in FNMA greater than 15° perceived the external rotation of the foot progression angle after TKA. All four patients had an increase in tibial torsion larger than 10°.

Conclusion: Our study shows that the tibiofemoral synchronization technique less likely affects the tibial torsion after primary TKA.
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http://dx.doi.org/10.1007/s00167-020-06429-zDOI Listing
January 2021

Outcome and status of postcardiac arrest care in Korea: results from the Korean Hypothermia Network prospective registry.

Clin Exp Emerg Med 2020 Dec 31;7(4):250-258. Epub 2020 Dec 31.

Department of Emergency Medicine, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Korea.

Objective: High-quality intensive care, including targeted temperature management (TTM) for patients with postcardiac arrest syndrome, is a key element for improving outcomes after out-of-hospital cardiac arrest (OHCA). We aimed to assess the status of postcardiac arrest syndrome care, including TTM and 6-month survival with neurologically favorable outcomes, after adult OHCA patients were treated with TTM, using data from the Korean Hypothermia Network prospective registry.

Methods: We used the Korean Hypothermia Network prospective registry, a web-based multicenter registry that includes data from 22 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TTM between October 2015 and December 2018 were included. The primary outcome was neurological outcome at 6 months.

Results: Of the 1,354 registered OHCA survivors treated with TTM, 550 (40.6%) survived 6 months, and 413 (30.5%) had good neurological outcomes. We identified 839 (62.0%) patients with preClinsumed cardiac etiology. A total of 937 (69.2%) collapses were witnessed, shockable rhythms were demonstrated in 482 (35.6%) patients, and 421 (31.1%) patients arrived at the emergency department with prehospital return of spontaneous circulation. The most common target temperature was 33°C, and the most common target duration was 24 hours.

Conclusion: The survival and good neurologic outcome rates of this prospective registry show great improvements compared with those of an earlier registry. While the optimal target temperature and duration are still unknown, the most common target temperature was 33°C, and the most common target duration was 24 hours.
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http://dx.doi.org/10.15441/ceem.20.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808836PMC
December 2020

Effects of Ultraviolet Light Irradiation on Silk Fibroin Films Prepared under Different Conditions.

Biomolecules 2021 Jan 7;11(1). Epub 2021 Jan 7.

Sericultural and Apicultural Materials Division, National Institute of Agricultural Sciences, RDA, Wanju-gun 55365, Korea.

Silk fibroin (SF)-based materials are exposed to both natural and artificial ultraviolet (UV) light during preparation or administration. However, the effects of UV irradiation on SF films prepared under different conditions have not yet been described in detail. In this study, four SF films with different molecular weight (MW) distribution were fabricated using SF solutions, which were prepared by dissolving degummed SF for 0.5-24 h. We observed UV (365 nm) irradiation on SF films induced the increase of yellowness and absorbance at 310 nm of SF films, indicating the formation of new photo-products and di-tyrosine bonds by photo-oxidation. Due to di-tyrosine cross-links between SF chains, UV-irradiated SF films were not fully dissociated in urea solution. In addition to formation of new products, UV reduced the crystallinity of SF films by breaking hydrogen bonds of β-sheet conformation. Unlike the UV-induced decomposition of physical interactions, UV did not affect the covalent bonds (i.e., peptide bonds). Through these experiments, we could expect that SF with higher MW was more susceptible and SF with lower MW was more resistant to UV-induced photo-oxidation and photo-degradation. These results provide useful information about UV-induced aging of SF-based materials under natural sunlight and UV irradiating conditions.
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http://dx.doi.org/10.3390/biom11010070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825685PMC
January 2021

Evaluation of a Fully Automated Antinuclear Antibody Indirect Immunofluorescence Assay in Routine Use.

Front Immunol 2020 4;11:607541. Epub 2020 Dec 4.

Department of Laboratory Medicine, Chonnam National University Hospital, Gwangju, South Korea.

Indirect immunofluorescence assay (IFA) using HEp-2 cells as a substrate is the gold standard for detecting antinuclear antibodies (ANA) in patient serum. However, the ANA IFA has labor-intensive nature of the procedure and lacks adequate standardization. To overcome these drawbacks, the automation has been developed and implemented to the clinical laboratory. The purposes of this study were to evaluate the analytical performance of a fully automated Helios ANA IFA analyzer in a real-life laboratory setting, and to compare the time and the cost of ANA IFA testing before and after adopting the Helios system. A total of 3,276 consecutive serum samples were analyzed for ANA using the Helios system from May to August 2019. The positive/negative results, staining patterns, and endpoint titers were compared between Helios and visual readings. Furthermore, the turnaround time and the number of wells used were compared before and after the introduction of Helios system. Of the 3,276 samples tested, 748 were positive and 2,528 were negative based on visual readings. Using visual reading as the reference standard, the overall relative sensitivity, relative specificity, and concordance of Helios reading were 73.3, 99.4, and 93.4% ( = 0.80), respectively. For pattern recognition, the overall agreement was 70.1% (298/425) for single patterns, and 72.4% (89/123) for mixed patterns. For titration, there was an agreement of 75.9% (211/278) between automated and classical endpoint titers by regarding within ± one titer difference as acceptable. Helios significantly shortened the median turnaround time from 100.6 to 55.7 h ( < 0.0001). Furthermore, routine use of the system reduced the average number of wells used per test from 4 to 1.5. Helios shows good agreement in distinguishing between positive and negative results. However, it still has limitations in positive/negative discrimination, pattern recognition, and endpoint titer prediction, requiring additional validation of results by human observers. Helios provides significant advantages in routine laboratory ANA IFA work in terms of labor, time, and cost savings. We hope that upgrading and developing softwares with more reliable capabilities will allow automated ANA IFA analyzers to be fully integrated into the routine operations of the clinical laboratory.
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http://dx.doi.org/10.3389/fimmu.2020.607541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746920PMC
December 2020

Toward Biomimetic Scaffolds for Tissue Engineering: 3D Printing Techniques in Regenerative Medicine.

Front Bioeng Biotechnol 2020 4;8:586406. Epub 2020 Nov 4.

Center for Biomaterials, Korea Institute of Science and Technology, Seoul, South Korea.

Three-dimensional (3D) printing technology allows fabricating complex and precise structures by stacking materials layer by layer. The fabrication method has a strong potential in the regenerative medicine field to produce customizable and defect-fillable scaffolds for tissue regeneration. Plus, biocompatible materials, bioactive molecules, and cells can be printed together or separately to enhance scaffolds, which can save patients who suffer from shortage of transplantable organs. There are various 3D printing techniques that depend on the types of materials, or inks, used. Here, different types of organs (bone, cartilage, heart valve, liver, and skin) that are aided by 3D printed scaffolds and printing methods that are applied in the biomedical fields are reviewed.
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http://dx.doi.org/10.3389/fbioe.2020.586406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671964PMC
November 2020

AMD1 is required for the maintenance of leukemic stem cells and promotes chronic myeloid leukemic growth.

Oncogene 2021 Jan 17;40(3):603-617. Epub 2020 Nov 17.

Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan, Republic of Korea.

Polyamines are critical elements in mammals, but it remains unknown whether adenosyl methionine decarboxylase (AMD1), a rate-limiting enzyme in polyamine synthesis, is required for myeloid leukemia. Here, we found that leukemic stem cells (LSCs) were highly differentiated, and leukemia progression was severely impaired in the absence of AMD1 in vivo. AMD1 was highly upregulated as chronic myeloid leukemia (CML) progressed from the chronic phase to the blast crisis phase, and was associated with the poor prognosis of CML patients. In addition, the pharmacological inhibition of AMD1 by AO476 treatment resulted in a robust reduction of the progression of leukemic cells both in vitro and in vivo. Mechanistically, AMD1 depletion induced loss of mitochondrial membrane potential and accumulation of reactive oxygen species (ROS), resulting in the differentiation of LSCs via oxidative stress and aberrant activation of unfolded protein response (UPR) pathway, which was partially rescued by the addition of polyamine. These results indicate that AMD1 is an essential element in the progression of myeloid leukemia and could be an attractive target for the treatment of the disease.
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http://dx.doi.org/10.1038/s41388-020-01547-xDOI Listing
January 2021

Expandable and implantable bioelectronic complex for analyzing and regulating real-time activity of the urinary bladder.

Sci Adv 2020 Nov 11;6(46). Epub 2020 Nov 11.

KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.

Underactive bladder or detrusor underactivity (DUA), that is, not being able to micturate, has received less attention with little research and remains unknown or limited on pathological causes and treatments as opposed to overactive bladder, although the syndrome may pose a risk of urinary infections or life-threatening kidney damage. Here, we present an integrated expandable electronic and optoelectronic complex that behaves as a single body with the elastic, time-dynamic urinary bladder with substantial volume changes up to ~300%. The system configuration of the electronics validated by the theoretical model allows conformal, seamless integration onto the urinary bladder without a glue or suture, enabling precise monitoring with various electrical components for real-time status and efficient optogenetic manipulation for urination at the desired time. In vivo experiments using diabetic DUA models demonstrate the possibility for practical uses of high-fidelity electronics in clinical trials associated with the bladder and other elastic organs.
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http://dx.doi.org/10.1126/sciadv.abc9675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673729PMC
November 2020

Atomic layer deposition of tungsten sulfide using a new metal-organic precursor and HS: thin film catalyst for water splitting.

Nanotechnology 2021 Feb;32(7):075405

School of Materials Science and Engineering, Yeungnam University, 214-1, Dae-dong, Gyeongsan, Gyeongsangbuk-do 38541, Republic of Korea.

Transition metal dichalcogenides (TMDs) are extensively researched in the past few years due to their two-dimensional layered structure similar to graphite. This group of materials offers tunable optoelectronic properties depending on the number of layers and therefore have a wide range of applications. Tungsten disulfide (WS) is one of such TMDs that has been studied relatively less compared to MoS. Herein, WS thin films are grown on several types of substrates by atomic layer deposition (ALD) using a new metal-organic precursor [tris(hexyne) tungsten monocarbonyl, W(CO)(CHCHC≡CCHCH)] and HS molecules at a relatively low temperature of 300 °C. The typical self-limiting film growth by varying both, precursor and reactant, is obtained with a relatively high growth per cycle value of ∼0.13 nm. Perfect growth linearity with negligible incubation period is also evident in this ALD process. While the as-grown films are amorphous with considerable S-deficiency, they can be crystallized as h-WS film by post-annealing in the HS atmosphere above 700 °C as observed from x-ray diffractometry analysis. Several other analyses like Raman and x-ray photoelectron spectroscopy, transmission electron microscopy, UV-vis. spectroscopy are performed to find out the physical, optical, and microstructural properties of as-grown and annealed films. The post-annealing in HS helps to promote the S content in the film significantly as confirmed by the Rutherford backscattering spectrometry. Extremely thin (∼4.5 nm), as-grown WS films with excellent conformality (∼100% step coverage) are achieved on the dual trench substrate (minimum width: 15 nm, aspect ratio: 6.3). Finally, the thin films of WS (as-grown and 600/700 °C annealed) on W/Si and carbon cloth substrate are investigated for electrochemical hydrogen evolution reaction (HER). The as-grown WS shows poor performance towards HER and is attributed to the S-deficiency, amorphous character, and oxygen contamination of the WS film. Annealing the WS film at 700 °C results in the formation of a crystalline layered WS phase, which significantly improves the HER performance of the electrode. The study reveals the importance of sulfur content and crystallinity on the HER performance of W-based sulfides.
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http://dx.doi.org/10.1088/1361-6528/abc50bDOI Listing
February 2021

Organ-Level Functional 3D Tissue Constructs with Complex Compartments and their Preclinical Applications.

Adv Mater 2020 Dec 26;32(51):e2002096. Epub 2020 Oct 26.

KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.

There is an increasing interest in organ-level 3D tissue constructs, owing to their mirroring of in vivo-like features. This has resulted in a wide range of preclinical applications to obtain cell- or tissue-specific responses. Additionally, the development and improvement of sophisticated technologies, such as organoid generation, microfluidics, hydrogel engineering, and 3D printing, have enhanced 3D tissue constructs to become more elaborate. In particular, recent studies have focused on including complex compartments, i.e., vascular and innervation structured 3D tissue constructs, which mimic the nature of the human body in that all tissues/organs are interconnected and physiological phenomena are mediated through vascular and neural systems. Here, the strategies are categorized according to the number of dimensions (0D, 1D, 2D, and 3D) of the starting materials for scaling up, and novel approaches to introduce increased complexity in 3D tissue constructs are highlighted. Recent advances in preclinical applications are also investigated to gain insight into the future direction of 3D tissue construct research. Overcoming the challenges in improving organ-level functional 3D tissue constructs both in vitro and in vivo will ultimately become a life-saving tool in the biomedical field.
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http://dx.doi.org/10.1002/adma.202002096DOI Listing
December 2020

Conditioned Medium from Canine Amniotic Membrane-Derived Mesenchymal Stem Cells Improved Dog Sperm Post-Thaw Quality-Related Parameters.

Animals (Basel) 2020 Oct 16;10(10). Epub 2020 Oct 16.

Department of Theriogenology and Biotechnologies, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

This study investigated the effects of conditioned medium (CM) from canine amniotic membrane-derived MSCs (cAMSCs) on dog sperm cryopreservation. For this purpose, flow cytometry analysis was performed to characterize cAMSCs. The CM prepared from cAMSCs was subjected to proteomic analysis for the identification of proteins present in the medium. Sperm samples were treated with freezing medium supplemented with 0%, 5%, 10%, and 15% of the CM, and kinetic parameters were evaluated after 4-6 h of chilling at 4 °C to select the best concentration before proceeding to cryopreservation. Quality-related parameters of frozen-thawed sperm were investigated, including motility; kinetic parameters; viability; integrity of the plasma membrane, chromatin, and acrosome; and mitochondrial activity. The results showed that 10% of the CM significantly enhanced motility, viability, mitochondrial activity, and membrane integrity ( < 0.05); however, the analysis of chromatin and acrosome integrity showed no significant differences between the treatment and control groups. Therefore, we concluded that the addition of 10% CM derived from cAMSC in the freezing medium protected dog sperm during the cryopreservation process.
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http://dx.doi.org/10.3390/ani10101899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603003PMC
October 2020

Utility of an Automatic Vision-Based Examination System (AVE-562) for the Detection of Eggs in Stool.

Ann Lab Med 2021 Mar;41(2):221-224

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

Stool examination is the gold standard for the detection of intestinal parasites. We assessed the performance of a newly developed AVE-562 analyzer (AVE Science & Technology Co., Hunan, China) for the vision-based detection of eggs of -the most common intestinal parasite in Korea-in stool samples. In total, 30 stool samples with a high or low egg count or without eggs (as negative control samples) (N=10 each) were prepared and analyzed. The performance of the AVE-562 analyzer was compared with that of the formalin-ether concentration (FEC) method. The overall correct identification rate of the AVE-562 analyzer based on FEC results was 66.6%. The sensitivity, specificity, positive predictive value, and negative predictive value of the AVE-562 analyzer for detecting C. sinensis eggs were 36.4%, 100.0%, 100.0%, and 73.1%, respectively. The average time required to run five tests simultaneously was 27 min using the AVE-562 analyzer and 58 min using the FEC method. Although the AVE-562 analyzer enables rapid and convenient stool examination, its sensitivity needs to be improved, particularly considering the prevalence of low-burden infection in Korea.
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http://dx.doi.org/10.3343/alm.2021.41.2.221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591289PMC
March 2021

Performance Evaluation of VITEK MS for the Identification of a Wide Spectrum of Clinically Relevant Filamentous Fungi Using a Korean Collection.

Ann Lab Med 2021 Mar;41(2):214-220

Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.

The correct identification of filamentous fungi is challenging. We evaluated the performance of the VITEK MS v3.0 system (bioMérieux, Marcy-l'Étoile, France) for the identification of a wide spectrum of clinically relevant filamentous fungi using a Korean collection. Strains that were added to the upgraded v3.2 database were additionally identified by the VITEK MS v3.2 system. Of the 105 tested isolates, including 37 (nine species), 41 dermatophytes (seven species), and 27 other molds (17 species), 43 (41.0%) showed "no identification" or "multiple species identification" results at the initial VITEK MS testing; these isolates were retested using the same method. Compared with sequence-based identification, the correct identification rate using VITEK MS for , dermatophytes, other molds, and total mold isolates was 67.6%, 56.1%, 48.1%, and 58.1% at the initial testing and 94.6%, 78.0%, 55.6%, and 78.1% with retesting, respectively. Following retesting, 19 (18.1%) and two (1.9%) isolates showed "no identification" and "misidentification" results, respectively. VITEK MS reliably identified various filamentous fungi recovered in Korea, with a very low rate of misidentification.
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http://dx.doi.org/10.3343/alm.2021.41.2.214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591280PMC
March 2021

Pharmaceutical Efficacy of Gypenoside LXXV on Non-Alcoholic Steatohepatitis (NASH).

Biomolecules 2020 10 8;10(10). Epub 2020 Oct 8.

MODNBIO Inc. digital road 34, Kolon Science Valley I, Guro-gu, Seoul 08378, Korea.

Ginsenosides have offered a wide array of beneficial roles in the pharmacological regulation of hepatic metabolic syndromes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), and obesity. Of the numerous ginsenosides, Rg3 has been widely investigated, but there have been few studies of gypenosides (Gyp). Particularly, no study on Gyp LXXV has been reported to date. Here, to firstly explore the pharmacological effects of Gyp LXXV against NASH and the related mechanism, methionine- and choline-deficient (MCD) diet-induced NASH mice and hepatic cells (stellate cells, hepatic macrophages, and hepatocytes) were selected. Gyp LXXV exhibited markedly alleviated MCD diet-induced hepatic injury, inflammation, and fibrosis by down-regulating hepatic fibrosis markers such as α-smooth muscle actin(α-SMA), collagen1, transforming growth factors-β (TGF-β1), tumor necrosis factor-α (TNF-α), MCP-1, interleukin (IL)-1β, nuclear factor κB (NFκB), and GRP78. Remarkably, histopathological studies confirmed that 15 mg/kg of Gyp LXXV administration to MCD diet-induced mice led to effective prevention of liver injury, lipid accumulation, and activation of hepatic macrophages, indicating that Gyp LXXV might be a potential anti-NASH drug.
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http://dx.doi.org/10.3390/biom10101426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599508PMC
October 2020

Adult-Onset Neuronal Intranuclear Inclusion Disease: First Korean Case Confirmed by Skin Biopsy.

J Clin Neurol 2020 Oct;16(4):720-722

Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3988/jcn.2020.16.4.720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541984PMC
October 2020

Deep brain optogenetics without intracranial surgery.

Nat Biotechnol 2021 02 5;39(2):161-164. Epub 2020 Oct 5.

Department of Bioengineering, Stanford University, Stanford, CA, USA.

Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm with millisecond precision. Using systemic viral delivery of ChRmine, we demonstrate behavioral modulation without surgery, enabling implant-free deep brain optogenetics.
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http://dx.doi.org/10.1038/s41587-020-0679-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878426PMC
February 2021

Augmented peripheral nerve regeneration through elastic nerve guidance conduits prepared using a porous PLCL membrane with a 3D printed collagen hydrogel.

Biomater Sci 2020 Nov 5;8(22):6261-6271. Epub 2020 Oct 5.

Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.

Peripheral nerve injury results in significant sensory and motor functional deficits. Although direct neurorrhaphy in the early phase may reduce its devastating effects, direct end-to-end neurorrhaphy is sometimes impossible owing to a defect at the injured site of the nerve. Autogenous nerve graft is a primary consideration for peripheral nerve defects; however, significant morbidity of the donor site is inevitable. Recently, the treatment using engineered synthetic nerve conduits has been regarded as a promising strategy to promote the regeneration of peripheral nerve defects. In this study, we developed longitudinally oriented collagen hydrogel-grafted elastic nerve guidance conduits (NGC) to reconstruct sciatic nerve defects. An elastic NGC was prepared by using poly(lactide-co-caprolactone) (PLCL), and electrospun PLCL was adopted to fabricate nanoporous structures with appropriate permeability for nerve regeneration. Oriented collagen hydrogels were prepared by the 3D printing method to achieve a microscale hydrogel pattern. Based on sciatic nerve injury models in rats, we confirmed the beneficial effects of the NGC with 3D printed collagen hydrogel on axonal regeneration and remyelination along with superior functional recovery in comparison with the NGC filled with the bulk collagen hydrogel. It is believed that the aligned collagen hydrogels provide a preferable environment for nerve regeneration, functioning as an oriented guidance path. In conclusion, the PLCL nerve guide conduit containing a 3D printed aligned collagen hydrogel can be useful for peripheral nerve regeneration.
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http://dx.doi.org/10.1039/d0bm00847hDOI Listing
November 2020

Neuron-specific enolase and neuroimaging for prognostication after cardiac arrest treated with targeted temperature management.

PLoS One 2020 1;15(10):e0239979. Epub 2020 Oct 1.

Department of Emergency Medicine, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Background: Prognostication after cardiac arrest (CA) needs a multimodal approach, but the optimal method is not known. We tested the hypothesis that the combination of neuron-specific enolase (NSE) and neuroimaging could improve outcome prediction after CA treated with targeted temperature management (TTM).

Methods: A retrospective observational cohort study was performed on patients who underwent at least one NSE measurement between 48 and 72 hr; received both a brain computed tomography (CT) scan within 24 hr and diffusion-weighted magnetic resonance imaging (DW-MRI) within 7 days after return of spontaneous circulation (ROSC); and were treated with TTM after out-of-hospital CA between 2009 and 2017 at the Seoul St. Mary's Hospital in Korea. The primary outcome was a poor neurological outcome at 6 months after CA, defined as a cerebral performance category of 3-5.

Results: A total of 109 subjects underwent all three tests and were ultimately included in this study. Thirty-four subjects (31.2%) experienced good neurological outcomes at 6 months after CA. The gray matter to white matter attenuation ratio (GWR) was weakly correlated with the mean apparent diffusion coefficient (ADC), PV400 and NSE (Spearman's rho: 0.359, -0.362 and -0.263, respectively). NSE was strongly correlated with the mean ADC and PV400 (Spearman's rho: -0.623 and 0.666, respectively). Serum NSE had the highest predictive value among the single parameters (area under the curve (AUC) 0.912, sensitivity 70.7% for maintaining 100% specificity). The combination of a DWI parameter (mean ADC or PV400) and NSE had better prognostic performance than the combination of the CT parameter (GWR) and NSE. The addition of the GWR to a DWI parameter and NSE did not improve the prediction of neurological outcomes.

Conclusion: The GWR (≤ 24 hr) is weakly correlated with the mean ADC (≤ 7 days) and NSE (highest between 48 and 72 hr). The combination of a DWI parameter and NSE has better prognostic performance than the combination of the GWR and NSE. The addition of the GWR to a DWI parameter and NSE does not improve the prediction of neurological outcomes after CA treatment with TTM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239979PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529296PMC
November 2020

Four-Week, Home-Based, Robot Cognitive Intervention for Patients with Mild Cognitive Impairment: a Pilot Randomized Controlled Trial.

Dement Neurocogn Disord 2020 Sep;19(3):96-107

Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.

Background And Purpose: Previous studies suggest that cognitive intervention can mitigate the development of dementia in patients with mild cognitive impairment (MCI). However, the previous cognitive intervention was mostly provided as a group session, in which MCI patients sometimes had difficulty in regularly attending sessions or were reluctant to participate in group-based classes. Additionally, experienced instructors for traditional cognitive intervention may be unavailable in some chronic-care facilities or community centers. Considering these reasons, we have developed 5 programs for home-based cognitive intervention using a personal robot for MCI patients. In this preliminary study, we aimed to demonstrate the effects of our newly developed home-based cognitive intervention with robots on cognitive function in MCI patients.

Methods: We conducted a single-blind randomized controlled trial enrolling 46 MCI patients. Participants were randomized into 2 groups: the robot cognitive intervention (robot) (=24) group and without cognitive intervention (control) (=22) group. The interventions comprised 60-min sessions per day for 4 weeks. The primary outcome was the change in cognitive function measured using the Cambridge Neuropsychological Test Automated Battery.

Results: There were no significant baseline demographic or clinical differences between the robot and control groups. After the 4-week cognitive intervention, the robot group showed greater improvement in working memory than did the control group.

Conclusions: Our home-based cognitive intervention with a personal robot improved the working memory in MCI patients. Further studies with larger samples and longer study periods are required to demonstrate the effects of these programs in other cognitive domains in MCI patients.
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http://dx.doi.org/10.12779/dnd.2020.19.3.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521954PMC
September 2020

Analysis of Adverse Drug Reactions with Carbamazepine and Oxcarbazepine at a Tertiary Care Hospital.

Yonsei Med J 2020 Oct;61(10):875-879

Department of Orofacial Pain and Oral Medicine, Yonsei University College of Dentistry, Seoul, Korea.

Purpose: To describe adverse drug reactions (ADRs) to carbamazepine (CBZ) and oxcarbazepine (OXC), including severe cutaneous ADRs, at a tertiary care hospital over a 10-year period.

Materials And Methods: The frequency and clinical features of ADRs caused by CBZ and OXC were analyzed using the pharmacovigilance database and spontaneous ADR reporting data of Yonsei University Severance Hospital & Dental Hospital (Seoul, Korea) from January 1, 2010 to January 31, 2020.

Results: Among 10419 cases prescribed CBZ and OXC, 204 ADR cases were reported. The incidences of ADRs were 1.8% and 2.2% for CBZ and OXC respectively, with no significant difference (=0.169). The most common clinical presentations were skin disorders. Female patients had relatively more frequent ADRs than male patients. Although mild skin ADRs were more frequent with OXC, nervous system disorders, general disorders, and hepatobiliary disorders occurred more often with CBZ. There were six reports of severe cutaneous adverse reactions to CBZ, while OXC had none. Both CBZ and OXC caused ADRs at daily doses lower than the recommended initial dose.

Conclusion: Due to lower incidence of severe ADRs with OXC than CBZ, we suggest OXC as a first-line prescription.
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http://dx.doi.org/10.3349/ymj.2020.61.10.875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515781PMC
October 2020

Prenatal PM exposure and vitamin D-associated early persistent atopic dermatitis via placental methylation.

Ann Allergy Asthma Immunol 2020 12 21;125(6):665-673.e1. Epub 2020 Sep 21.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 μm to 2.5 μm (PM) and vitamin D on atopic dermatitis (AD) phenotypes have not been evaluated. DNA methylation and cord blood (CB) vitamin D could represent a plausible link between prenatal PM exposure and AD in an offspring.

Objective: To determine the critical windows of prenatal PM exposure on the AD phenotypes, if vitamin D modulated these effects, and if placental DNA methylation mediated these effects on AD in offspring.

Methods: Mother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PM was estimated by land-use regression models, and CB vitamin D was measured by chemiluminescence immunoassay. AD was identified by the parental report of a physician's diagnosis. We defined the following 4 AD phenotypes according to onset age (by the age of 2 years) and persistence (by the age of 3 years): early-onset transient and persistent, late onset, and never. Logistic regression analysis and Bayesian distributed lag interaction model were used. DNA methylation microarray was analyzed using an Infinium Human Methylation EPIC BeadChip (Illumina, San Diego, California) in placenta.

Results: PM exposure during the first trimester of pregnancy, especially during 6 to 7 weeks of gestation, was associated with early-onset persistent AD. This effect increased in children with low CB vitamin D, especially in those with PM exposure during 3 to 7 weeks of gestation. AHRR (cg16371648), DPP10 (cg19211931), and HLADRB1 (cg10632894) were hypomethylated in children with AD with high PM and low CB vitamin D.

Conclusion: Higher PM during the first trimester of pregnancy and low CB vitamin D affected early-onset persistent AD, and the most sensitive window was 6 to 7 weeks of gestation. Placental DNA methylation mediated this effect.
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http://dx.doi.org/10.1016/j.anai.2020.09.008DOI Listing
December 2020

The HLA-A*02:01:175 allele newly identified in a Korean hematopoietic stem cell donor by next-generation sequencing.

HLA 2021 Jan 27;97(1):62-64. Epub 2020 Sep 27.

Department of Laboratory Medicine, Chonnam National University Hospital and Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.

HLA-A*02:01:175 has a single synonymous nucleotide polymorphism when compared with HLA-A*02:01:01:01 [c165.G>C].
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http://dx.doi.org/10.1111/tan.14071DOI Listing
January 2021