Publications by authors named "Seung-Yeon Lee"

86 Publications

Microtechnology-based models: Mimicking liver function and pathophysiology.

APL Bioeng 2021 Dec 15;5(4):041505. Epub 2021 Oct 15.

Department of Chemical Engineering, Hongik University, Seoul 04066, South Korea.

The liver plays important roles in drug metabolism and homeostasis. The metabolism and biotransformation can not only affect the efficacy of drugs but also result in hepatotoxicity and drug-induced liver injury. Understanding the complex physiology of the liver and the pathogenetic mechanisms of liver diseases is essential for drug development. Conventional models have limitations in the ability to predict drug effects, due to the lack of physiological relevance. Recently, the liver-on-a-chip platform has been developed to reproduce the microarchitecture and environment of the liver. These efforts have improved the physiological relevance of the liver tissue used in the platform and have demonstrated its applicability to drug screening and disease models. In this review, we summarize the recent development of liver-on-a-chip models that closely mimic the liver environments and liver diseases.
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http://dx.doi.org/10.1063/5.0061896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520487PMC
December 2021

Voltage-gated calcium channels contribute to spontaneous glutamate release directly via nanodomain coupling or indirectly via calmodulin.

Prog Neurobiol 2022 Jan 22;208:102182. Epub 2021 Oct 22.

Department of Biomedical Sciences, Seoul National University College of Natural Science, Seoul, Republic of Korea; Department of Physiology, Seoul National University College of Natural Science, Seoul, Republic of Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Republic of Korea; Department of Brain and Cognitive Science, Seoul National University College of Natural Science, Seoul, Republic of Korea. Electronic address:

Neurotransmitter release occurs either synchronously with action potentials (evoked release) or spontaneously (spontaneous release). Whether the molecular mechanisms underlying evoked and spontaneous release are identical, especially whether voltage-gated calcium channels (VGCCs) can trigger spontaneous events, is still a matter of debate in glutamatergic synapses. To elucidate this issue, we characterized the VGCC dependence of miniature excitatory postsynaptic currents (mEPSCs) in various synapses with different coupling distances between VGCCs and synaptic vesicles, known as a critical factor in evoked release. We found that most of the extracellular calcium-dependent mEPSCs were attributable to VGCCs in cultured autaptic hippocampal neurons and the mature calyx of Held where VGCCs and vesicles were tightly coupled. Among loosely coupled synapses, mEPSCs were not VGCC-dependent at immature calyx of Held and CA1 pyramidal neuron synapses, whereas VGCCs contribution was significant at CA3 pyramidal neuron synapses. Interestingly, the contribution of VGCCs to spontaneous glutamate release in CA3 pyramidal neurons was abolished by a calmodulin antagonist, calmidazolium. These data suggest that coupling distance between VGCCs and vesicles determines VGCC dependence of spontaneous release at tightly coupled synapses, yet VGCC contribution can be achieved indirectly at loosely coupled synapses.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102182DOI Listing
January 2022

Performance evaluation in [18F]Florbetaben brain PET images classification using 3D Convolutional Neural Network.

PLoS One 2021 20;16(10):e0258214. Epub 2021 Oct 20.

Department of Translational Biomedical Sciences, Dong-A University, Busan, Korea.

High accuracy has been reported in deep learning classification for amyloid brain scans, an important factor in Alzheimer's disease diagnosis. However, the possibility of overfitting should be considered, as this model is fitted with sample data. Therefore, we created and evaluated an [18F]Florbetaben amyloid brain positron emission tomography (PET) scan classification model with a Dong-A University Hospital (DAUH) dataset based on a convolutional neural network (CNN), and performed external validation with the Alzheimer's Disease Neuroimaging Initiative dataset. Spatial normalization, count normalization, and skull stripping preprocessing were performed on the DAUH and external datasets. However, smoothing was only performed on the external dataset. Three types of models were used, depending on their structure: Inception3D, ResNet3D, and VGG3D. After training with 80% of the DAUH dataset, an appropriate model was selected, and the rest of the DAUH dataset was used for model evaluation. The generalization potential of the selected model was then validated using the external dataset. The accuracy of the model evaluation for Inception3D, ResNet3D, and VGG3D was 95.4%, 92.0%, and 97.7%, and the accuracy of the external validation was 76.7%, 67.1%, and 85.3%, respectively. Inception3D and ResNet3D were retrained with the external dataset; then, the area under the curve was compared to determine the binary classification performance with a significance level of less than 0.05. When external validation was performed again after fine tuning, the performance improved to 15.3%p for Inception3D and 16.9%p for ResNet3D. In [18F]Florbetaben amyloid brain PET scan classification using CNN, the generalization potential can be seen through external validation. When there is a significant difference between the model classification performance and the external validation, changing the model structure or fine tuning the model can help improve the classification performance, and the optimal model can also be found by collaborating through a web-based open platform.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258214PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528306PMC
November 2021

Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance.

J Clin Invest 2021 12;131(23)

Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea.

Insulin resistance is a cornerstone of obesity-related complications such as type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease. A high rate of lipolysis is known to be associated with insulin resistance, and inhibiting adipose tissue lipolysis improves obesity-related insulin resistance. Here, we demonstrate that inhibition of serotonin (5-hydroxytryptamine [5-HT]) signaling through serotonin receptor 2B (HTR2B) in adipose tissues ameliorates insulin resistance by reducing lipolysis in visceral adipocytes. Chronic high-fat diet (HFD) feeding increased Htr2b expression in epididymal white adipose tissue, resulting in increased HTR2B signaling in visceral white adipose tissue. Moreover, HTR2B expression in white adipose tissue was increased in obese humans and positively correlated with metabolic parameters. We further found that adipocyte-specific Htr2b-knockout mice are resistant to HFD-induced insulin resistance, visceral adipose tissue inflammation, and hepatic steatosis. Enhanced 5-HT signaling through HTR2B directly activated lipolysis through phosphorylation of hormone-sensitive lipase in visceral adipocytes. Moreover, treatment with a selective HTR2B antagonist attenuated HFD-induced insulin resistance, visceral adipose tissue inflammation, and hepatic steatosis. Thus, adipose HTR2B signaling could be a potential therapeutic target for treatment of obesity-related insulin resistance.
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http://dx.doi.org/10.1172/JCI145331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631597PMC
December 2021

Rutaecarpine Increases Nitric Oxide Synthesis via eNOS Phosphorylation by TRPV1-Dependent CaMKII and CaMKKβ/AMPK Signaling Pathway in Human Endothelial Cells.

Int J Mol Sci 2021 Aug 30;22(17). Epub 2021 Aug 30.

College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.

Rutaecarpine (RUT) is a bioactive alkaloid isolated from the fruit of that exerts a cellular protective effect. However, its protective effects on endothelial cells and its mechanism of action are still unclear. In this study, we demonstrated the effects of RUT on nitric oxide (NO) synthesis via endothelial nitric oxide synthase (eNOS) phosphorylation in endothelial cells and the underlying molecular mechanisms. RUT treatment promoted NO generation by increasing eNOS phosphorylation. Additionally, RUT induced an increase in intracellular Ca concentration and phosphorylation of Ca/calmodulin-dependent protein kinase kinase β (CaMKKβ), AMP-activated protein kinase (AMPK), and Ca/calmodulin-dependent kinase II (CaMKII). Inhibition of transient receptor potential vanilloid type 1 (TRPV1) attenuated RUT-induced intracellular Ca concentration and phosphorylation of CaMKII, CaMKKβ, AMPK, and eNOS. Treatment with KN-62 (a CaMKII inhibitor), Compound C (an AMPK inhibitor), and STO-609 (a CaMKKβ inhibitor) suppressed RUT-induced eNOS phosphorylation and NO generation. Interestingly, RUT attenuated the expression of ICAM-1 and VCAM-1 induced by TNF-α and inhibited the inflammation-related NF-κB signaling pathway. Taken together, these results suggest that RUT promotes NO synthesis and eNOS phosphorylation via the Ca/CaMKII and CaM/CaMKKβ/AMPK signaling pathways through TRPV1. These findings provide evidence that RUT prevents endothelial dysfunction and benefit cardiovascular health.
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http://dx.doi.org/10.3390/ijms22179407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431268PMC
August 2021

Development of Food Literacy Assessment Tool Targeting Adults With Low Income.

J Nutr Educ Behav 2021 Nov 20;53(11):966-976. Epub 2021 Aug 20.

Department of Rehabilitation, Exercise, and Nutrition Sciences, College of Allied Health Sciences, University of Cincinnati, Cincinnati, OH. Electronic address:

Objective: Develop and test validity and reliability of the Food Literacy Assessment Tool (FLitT) in adults with low income.

Design: Face validity was tested using cognitive interviews, content validity using expert review, and internal consistency reliability and test-retest reliability based on 2 administrations of the survey.

Setting: Urban choice food pantry in Cincinnati, OH.

Participants: There were 10 and 98 adults with low income for the cognitive interview and survey, respectively VARIABLES MEASURED: Knowledge, self-efficacy, and behavior required to plan and manage, select, prepare, and eat in relation to food.

Analysis: Cronbach α and Kuder-Richardson Formula 20 for internal consistency reliability and intraclass correlation coefficient (ICC) for test-retest reliability.

Results: Cognitive interviews and expert feedback suggested modifications to improve the clarity of FLitT and offer more response options. Testing shows acceptable internal consistency in self-efficacy (Cronbach α = 0.92) and behavior (Cronbach α = 0.90) but not in knowledge (Kuder-Richardson Formula 20 = 0.51). The FLitT shows acceptable test-retest reliability for knowledge (ICC = 0.84), self-efficacy (ICC = 0.70), and behavior (ICC = 0.93).

Conclusions And Implications: The FLitT was developed and tested for face and content validity and internal and test-retest reliability in adults with low income. Additional research is needed to conduct a second round of face validity and test construct validity using factor analysis with a larger size.
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http://dx.doi.org/10.1016/j.jneb.2021.05.007DOI Listing
November 2021

Rare case of bullous pemphigoid occurring on atrophic centers of disseminated superficial porokeratosis lesions.

J Dermatol 2021 Nov 18;48(11):e530-e531. Epub 2021 Aug 18.

Department of Dermatology, School of Medicine, WonKwang University, Iksan, Korea.

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http://dx.doi.org/10.1111/1346-8138.16083DOI Listing
November 2021

Estrogen Aggravates Tumor Growth in a Diffuse Gastric Cancer Xenograft Model.

Pathol Oncol Res 2021 16;27:622733. Epub 2021 Apr 16.

Duksung Innovative Drug Center, Duksung Women's University, Seoul, Korea.

Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (), IQ motif containing E (), transient receptor potential cation channel subfamily M member 4 (), and structure-specific endonuclease subunit SLX4 () were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.
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http://dx.doi.org/10.3389/pore.2021.622733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262185PMC
January 2022

Calbindin regulates Kv4.1 trafficking and excitability in dentate granule cells via CaMKII-dependent phosphorylation.

Exp Mol Med 2021 07 7;53(7):1134-1147. Epub 2021 Jul 7.

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

Calbindin, a major Ca buffer in dentate granule cells (GCs), plays a critical role in shaping Ca signals, yet how it regulates neuronal function remains largely unknown. Here, we found that calbindin knockout (CBKO) mice exhibited dentate GC hyperexcitability and impaired pattern separation, which co-occurred with reduced K current due to downregulated surface expression of Kv4.1. Relatedly, manipulation of calbindin expression in HT22 cells led to changes in CaMKII activation and the level of surface localization of Kv4.1 through phosphorylation at serine 555, confirming the mechanism underlying neuronal hyperexcitability in CBKO mice. We also discovered that Ca buffering capacity was significantly reduced in the GCs of Tg2576 mice to the level of CBKO GCs, and this reduction was restored to normal levels by antioxidants, suggesting that calbindin is a target of oxidative stress. Our data suggest that the regulation of CaMKII signaling by Ca buffering is crucial for neuronal excitability regulation.
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http://dx.doi.org/10.1038/s12276-021-00645-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333054PMC
July 2021

Healthy measures: Feasibility study of a moderate carbohydrate weight management intervention.

Public Health Nurs 2021 Nov 16;38(6):1126-1130. Epub 2021 Jun 16.

Duquesne University, Pittsburgh, Pennsylvania, USA.

Background: People of all weights need to prevent changes that could lead to obesity, a leading public health issue.

Objective: To assess the feasibility of Healthy Measures, a moderate carbohydrate (160-300 g/d) nutrition education and behavioral intervention.

Design: An uncontrolled intervention feasibility study including in-person group meetings every 2 weeks for 3 months.

Sample: Fifteen participants of normal and overweight BMI.

Measurements: We assessed feasibility of recruitment, attendance, retention and satisfaction as well as anthropometric measures and social cognitive variables with Healthy Measures, a nutrition-focused intervention with moderate carbohydrate portions that also emphasizes self-monitoring of anthropometric measurements. An intent-to-treat analysis was used.

Results: Healthy Measures was feasible, with 13 participants (86.7%) completing pre- and post-intervention assessments. Eight participants lost or maintained weight (53.3%); four gained weight. Healthy eating self-efficacy increased overall (t = -2.54, p = .024). Increased protein and fat intake was associated with weight loss, while reduced protein, carbohydrate, and fat intake resulted in weight gain.

Conclusions: Healthy Measures shows promise for prevention of weight gain, with evidence of feasibility and positive outcomes. Further research is needed to establish efficacy relative to alternative approaches.
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http://dx.doi.org/10.1111/phn.12937DOI Listing
November 2021

A Case of the Safety and Efficacy of Guselkumab in Psoriasis with Alcoholic Liver Cirrhosis.

Ann Dermatol 2021 Feb 30;33(1):88-90. Epub 2020 Dec 30.

Department of Gastroenterology, Design Hospital, Jeonju, Korea.

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http://dx.doi.org/10.5021/ad.2021.33.1.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875222PMC
February 2021

Cancer-associated fibroblasts induce an aggressive phenotypic shift in non-malignant breast epithelial cells via interleukin-8 and S100A8.

J Cell Physiol 2021 10 21;236(10):7014-7032. Epub 2021 Mar 21.

Duksung Innovative Drug Center, College of Pharmacy, Duksung Women's University, Seoul, Korea.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with tumor progression in breast cancer. Although crosstalk between breast cancer cells and CAFs has been studied, the effect of CAFs on non-neoplastic breast epithelial cells is not fully understood to date. Here, we investigated the effect of CAFs on aggressive phenotypes in non-neoplastic MCF10A breast epithelial cells. CAFs induced epithelial-to-mesenchymal transition (EMT) and invasive phenotype in MCF10A cells. S100A8, a potential prognostic marker in several cancers, was markedly increased in MCF10A cells by CAFs. S100A8 was crucial for CAFs-induced invasive phenotype of MCF10A cells. Among cytokines increased by CAFs, interleukin (IL)-8 induced S100A8 through transcription factors p65 NF-κB and C/EBPβ. In a xenograft mouse model with MCF10A cells and CAFs, tumor was not developed, suggesting that coinjection with CAFs may not be sufficient for in vivo tumorigenicity of MCF10A cells. Xenograft mouse tumor models with MDA-MB-231 breast carcinoma cells provided an in vivo evidence for the effect of CAFs on breast cancer progression as well as a crucial role of IL-8 in tumor growth and S100A8 expression in vivo. Using a tissue microarray of human breast cancer, we showed that S100A8 expression was correlated with poor outcomes. S100A8 expression was more frequently detected in cancer-adjacent normal human breast tissues than in normal breast tissues. Together, this study elucidated a novel mechanism for the acquisition of invasive phenotype of non-neoplastic breast cells induced by CAFs, suggesting that targeting IL-8 and S100A8 may be an effective strategy against breast cancer.
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http://dx.doi.org/10.1002/jcp.30364DOI Listing
October 2021

Prevalence of and Factors Associated with School Bullying in Students with Autism Spectrum Disorder: A Cross-Cultural Meta-Analysis.

Yonsei Med J 2020 Nov;61(11):909-922

Center for ASD and Neurodevelopmental Disorders, University of California, San Francisco, CA, USA.

Through this meta-analysis, we sought to examine the prevalence of, risks for, and factors associated with bullying involvement (victimization, perpetration, perpetration-victimization) among students with autism spectrum disorder (ASD). Additionally, we attempted to examine sources of variance in the prevalence and effect sizes of bullying in students with ASD across studies. Systematic database and literature review identified 34 relevant studies (31 for Western countries, three for Eastern countries). Pooled prevalence estimates for victimization, perpetration, and perpetration-victimization in general were 67%, 29%, and 14%, respectively. The risk of victimization in students with ASD was significantly higher than that in typically developing students and students with other disabilities. Further, deficits in social interaction and communication, externalizing symptoms, internalizing symptoms, and integrated inclusive school settings were related to higher victimization, and externalizing symptoms were related to higher perpetration. Finally, moderation analyses revealed significant variations in the pooled prevalences thereof depending on culture, age, school settings, and methodological quality and in the pooled effect sizes according to publication year and methodological quality. Our results highlight needs for bullying intervention for students with ASD, especially those who are younger, are in an inclusive school setting, and have higher social difficulties and externalizing/internalizing symptoms; for intensive research of bullying experiences among students with ASD in Eastern countries; and for efforts to improve the methodological quality of such research.
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http://dx.doi.org/10.3349/ymj.2020.61.11.909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593096PMC
November 2020

Allogeneic Platelet-Rich Plasma Versus Corticosteroid Injection for the Treatment of Rotator Cuff Disease: A Randomized Controlled Trial.

J Bone Joint Surg Am 2020 Dec;102(24):2129-2137

Departments of Orthopedic Surgery (C.H.J., S.Y.L., and K.S.Y.), Biostatistics (S.O.), and Laboratory Medicine (S.S.), SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: The use of platelet-rich plasma (PRP) for the treatment of rotator cuff disease is still controversial. The purpose of the present study was to investigate the safety and efficacy of a fully characterized allogeneic pure PRP injection into the subacromial space of patients with rotator cuff disease in comparison with corticosteroid injection.

Methods: A 2-group, parallel, assessor-blinded, randomized controlled trial was conducted. A total of 60 patients with clinically and structurally diagnosed rotator cuff disease were randomly assigned to receive a subacromial injection of either 4 mL of allogeneic pure PRP or a 4-mL mixture of 1 mL of 40-mg/mL triamcinolone acetonide and 3 mL of 2% lidocaine under ultrasonographic guidance. The primary outcomes were safety and the Constant score at 1 month. The secondary outcomes were pain, range of motion, muscle strength, functional scores, and overall satisfaction and function.

Results: There were no treatment-related adverse events. The Constant score at 1 month did not significantly differ between the PRP and corticosteroid groups. At 6 months, the DASH (Disabilities of the Arm, Shoulder and Hand) score, overall function, and external rotation were significantly better in the PRP group than in the corticosteroid group, and the other clinical outcomes did not show significant differences. All pain measurements, the strength of the supraspinatus and infraspinatus, and 5 functional scores also improved slowly and steadily after injection, becoming significantly better at 6 months compared with those before the injection, whereas those in the corticosteroid group responded promptly but did not further improve.

Conclusions: Allogeneic PRP injections for the treatment of rotator cuff disease are safe but are not definitely superior to corticosteroid injections with respect to pain relief and functional improvement during 6 months. The DASH score, overall function, and external rotation were significantly better in the PRP group than in the steroid group at 6 months. Generally, PRP slowly but steadily reduced pain and improved function of the shoulder until 6 months, whereas corticosteroid did not.

Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.19.01411DOI Listing
December 2020

l-Tryptophan: Antioxidant as a Film-Forming Additive for a High-Voltage Cathode.

Langmuir 2020 03 16;36(11):2823-2828. Epub 2020 Mar 16.

Department of Mechanical Engineering, Gachon University, 1342 Sungnamdaero, Sujeong-Gu, Sungnam Si, Gyeonggi-do 13120, South Korea.

l-tryptophan (TrP) was investigated as a functional film-forming additive on a lithium-rich layered oxide cathode because it has a much lower oxidation potential than other common carbonate-based electrolytes. Owing to its prior oxidation to a base electrolyte, an artificial cathode-electrolyte interphase (CEI) was formed on the cathode surface, which could be confirmed via X-ray photoelectron spectroscopy and scanning electron microscopy and verified through density functional theory calculations. The functional film formed on the cathode surface suppressed the side reactions between the cathode and electrolyte during cell cycling. As a result, the film prevented CEI thickening and performance deterioration. The optimum weight of TrP was determined to be 0.4 wt % for obtaining the best performance.
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http://dx.doi.org/10.1021/acs.langmuir.0c00064DOI Listing
March 2020

Availability of Food Options and Nutrition Education in Local Food Pantries.

J Nutr Educ Behav 2020 05 22;52(5):492-502. Epub 2020 Feb 22.

Department of Rehabilitation, Exercise, and Nutrition Sciences, College of Allied Health Sciences, University of Cincinnati, Cincinnati, OH. Electronic address:

Objective: Explore the availability of food options and nutrition education at food pantries and identify the barriers to offering them to pantry clients.

Design: Cross-sectional, mixed-methods study.

Setting: Food pantry, Cincinnati, OH.

Participants: A total of 41 food pantry coordinators (aged 63.4 ± 9.1 years), recruited by e-mail/phone in an urban area.

Phenomenon Of Interest: Availability of food options and nutrition education and barriers to improving food options and providing nutrition education at food pantries.

Analysis: Survey data were collected using Qualtrics and analyzed using SPSS software. In-depth interviews were transcribed verbatim, transcripts were independently coded, and codes and themes were discussed until a consensus was reached.

Results: The availability of fresh produce, dairy, low-sodium canned vegetables, and whole grains were limited, and 10 food pantries (24%) offered nutrition education to their clients. Challenges to improving food options were lack of space and equipment for storage and transportation. Identified barriers to providing nutrition education included the lack of space, funding, personnel with nutrition expertise, and clients' low interest in nutrition education.

Conclusions And Implications: The availability of healthy food choices and nutrition education were limited at local food pantries. Collaborative efforts with community partners and nutrition experts may be necessary to overcome those barriers.
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http://dx.doi.org/10.1016/j.jneb.2019.12.013DOI Listing
May 2020

Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.

J Neurosci 2020 03 11;40(11):2200-2214. Epub 2020 Feb 11.

Department of Physiology,

The dentate gyrus (DG) in the hippocampus may play key roles in remembering distinct episodes through pattern separation, which may be subserved by the sparse firing properties of granule cells (GCs) in the DG. Low intrinsic excitability is characteristic of mature GCs, but ion channel mechanisms are not fully understood. Here, we investigated ionic channel mechanisms for firing frequency regulation in hippocampal GCs using male and female mice, and identified Kv4.1 as a key player. Immunofluorescence analysis showed that Kv4.1 was preferentially expressed in the DG, and its expression level determined by Western blot analysis was higher at 8-week than 3-week-old mice, suggesting a developmental regulation of Kv4.1 expression. With respect to firing frequency, GCs are categorized into two distinctive groups: low-frequency (LF) and high-frequency (HF) firing GCs. Input resistance ( ) of most LF-GCs is lower than 200 MΩ, suggesting that LF-GCs are fully mature GCs. Kv4.1 channel inhibition by intracellular perfusion of Kv4.1 antibody increased firing rates and gain of the input-output relationship selectively in LF-GCs with no significant effect on resting membrane potential and , but had no effect in HF-GCs. Importantly, mature GCs from mice depleted of Kv4.1 transcripts in the DG showed increased firing frequency, and these mice showed an impairment in contextual discrimination task. Our findings suggest that Kv4.1 expression occurring at late stage of GC maturation is essential for low excitability of DG networks and thereby contributes to pattern separation. The sparse activity of dentate granule cells (GCs), which is essential for pattern separation, is supported by high inhibitory inputs and low intrinsic excitability of GCs. Low excitability of GCs is thought to be attributable to a high K conductance at resting membrane potentials, but this study identifies Kv4.1, a depolarization-activated K channel, as a key ion channel that regulates firing of GCs without affecting resting membrane potentials. Kv4.1 expression is developmentally regulated and Kv4.1 currents are detected only in mature GCs that show low-frequency firing, but not in less mature high-frequency firing GCs. Furthermore, mice depleted of Kv4.1 transcripts in the dentate gyrus show impaired pattern separation, suggesting that Kv4.1 is crucial for sparse coding and pattern separation.
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http://dx.doi.org/10.1523/JNEUROSCI.1541-19.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083294PMC
March 2020

Annual Prevalence and Incidence of Schizophrenia and Similar Psychotic Disorders in the Republic of Korea: A National Health Insurance Data-Based Study.

Psychiatry Investig 2020 Jan 25;17(1):61-70. Epub 2020 Jan 25.

Institute of Public Health and Medical Service, Seoul National University Hospital, Seoul, Republic of Korea.

Objective: We conducted this study to address the incidence and prevalence of schizophrenia and similar psychosis in South Korea with Health Insurance Review and Assessment (HIRA) database.

Methods: We used HIRA database, which includes diagnostic information of nearly all Korean nationals to collect number of cases with diagnosis of schizophrenia and schizophrenia-similar disorders (SSP), including schizophreniform, acute/transient psychotic disorders, schizoaffective disorders, and other/unspecific nonorganic psychosis (ICD-10 codes F20/23/25/28/29) between 2010 and 2015. The annual prevalence and incidence were calculated using the population data from the Korean Statistical Office.

Results: The 12-month prevalence of SSP of Korea between 2010 and 2015 were 0.48-0.66%. The 12-month prevalence of schizophrenia were 0.40-0.52%; The annual incidence rates (IR) of SSP between 2010 and 2015 were 118.8-148.7 per 100,000 person-year (PY). For schizophrenia, IR per 100,000 PY were 77.6-88.5 between 2010 and 2015.

Conclusion: The 12-month prevalence found in the present study was higher than that reported in community-based epidemiologic studies in South Korea but similar to those from other countries. The annual incidence of SSP and schizophrenia was found to steadily increase and was higher than that of other countries. The high incidence rate observed in the current study needs to be studied further.
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http://dx.doi.org/10.30773/pi.2019.0041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992854PMC
January 2020

Relationship between Sedentary Time and Handgrip Strength in Healthy Korean Women: Korea National Health and Nutrition Examination Survey 2014-2016.

Korean J Fam Med 2020 Nov 6;41(6):422-426. Epub 2020 Jan 6.

Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: This study aimed to examine the association between sitting time and handgrip strength in healthy Korean women.

Methods: A total of 5,437 participants were included from the Korea National Health and Nutrition Examination Survey 2014-2016. The overall daily sitting time was estimated using health interview surveys, and handgrip strength was assessed using a digital hand dynamometer. The relationship between sitting time and handgrip strength was calculated with a weighted analysis of covariance after adjusting for confounding variables.

Results: Participants in each age group (19-39, 40-64, ≥65 years) were divided into three categories according to sitting time: ≤5, 6-9, and ≥10 h/d. The handgrip strength tended to decrease as sitting time increased after adjusting for age, body mass index, alcohol intake, cigarette smoking, resistance exercise, aerobic physical activity, household income, education level, hypertension, diabetes mellitus, dyslipidemia, and depression in all age groups (all P<0.001).

Conclusion: We observed the inverse relationship between sitting time and handgrip strength in healthy Korean women.
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http://dx.doi.org/10.4082/kjfm.19.0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700831PMC
November 2020

Understanding diversity and distribution of the insect assemblages associated with carrions.

J Forensic Leg Med 2019 Nov 29;68:101865. Epub 2019 Aug 29.

Department of the Biomedical Sciences, Kosin University, South Korea.

375 case studies from 120 publications published over the last three decades on forensic entomology were reviewed to determine how many carcass-associated insects have been described globally and which species are relatively important among carcass-associated insects. A total of 1213 carcass-associated insects belonging to 91 families of 10 orders were described from 375 case studies in nine habitat types of 30 countries with 24 subjects including humans and non-human animals. There were 564 and 515 species from the orders Diptera and Coleoptera, respectively, which was almost 90% of the total species recorded. The richness and distribution of dead body-associated insects considerably differed among countries, habitats, and dead body types. We propose some species based on criteria including distribution, occurrence frequency, and resource preference.
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http://dx.doi.org/10.1016/j.jflm.2019.101865DOI Listing
November 2019

The case for extended thromboprophylaxis in medically hospitalised patients - not yet made.

Eur J Prev Cardiol 2019 Mar 16:2047487319836572. Epub 2019 Mar 16.

1 Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.

Background: The role of extended thromboprophylaxis is established for surgical patients, but not yet for hospitalised medical patients.

Design: This systematic review and meta-analysis sought to explore the role of extended thromboprophylaxis for medically ill hospitalised patients.

Methods: Medline, EMBASE and Cochrane Libraries were searched and five randomised controlled trials were identified, comprising 20,046 extended and 20,078 standard duration thromboprophylaxis patients.

Results: Allocation to extended treatment, compared with standard duration therapy, significantly reduced the risk of symptomatic deep vein thrombosis (relative risk (RR) 0.47, 95% confidence interval (CI) 0.29-0.78, P = 0.003) and non-fatal pulmonary embolism (RR 0.59, 95% CI 0.39-0.91, P = 0.02). The risk of venous thromboembolism-related death was comparable between the extended and standard duration treatment groups (RR 0.81, 95% CI 0.6-1.09, P = 0.16). Extended treatment also doubled the risk of major bleeding (RR 2.04, 95% CI 1.42-2.91, P < 0.001), without significantly affecting the risk of intracranial bleeding or bleeding-associated death. The cost of preventing one symptomatic deep vein thrombosis and non-fatal pulmonary embolism was found to be £24,972 (€27,969) and £45,148 (€50,566), respectively, which outweigh the direct cost of managing established venous thromboembolism as previously reported.

Conclusions: Extended duration thromboprophylaxis caused a reduction in the risk of venous thromboembolic events, but also a numerically comparable increase in major bleeding. Further trials are required in high-risk subpopulations who may derive mortality benefits from treatment. Only then could a change in current policy and practice be supported.
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http://dx.doi.org/10.1177/2047487319836572DOI Listing
March 2019

A recurrent mutation in KCNQ4 in Korean families with nonsyndromic hearing loss and rescue of the channel activity by KCNQ activators.

Hum Mutat 2019 03 25;40(3):335-346. Epub 2018 Dec 25.

Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea.

Mutations in potassium voltage-gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to nonsyndromic hearing loss (NSHL), deafness nonsyndromic autosomal dominant 2 (DFNA2). To identify causative mutations of hearing loss in 98 Korean families, we performed whole exome sequencing. In four independent families with NSHL, we identified a cosegregating heterozygous missense mutation, c.140T>C (p.Leu47Pro), in KCNQ4. Individuals with the c.140T>C KCNQ4 mutation shared a haplotype flanking the mutated nucleotide, suggesting that this mutation may have arisen from a common ancestor in Korea. The mutant KCNQ4 protein could reach the plasma membrane and interact with wild-type (WT) KCNQ4, excluding a trafficking defect; however, it exhibited significantly decreased voltage-gated potassium channel activity and fast deactivation kinetics compared with WT KCNQ4. In addition, when co-expressed with WT KCNQ4, mutant KCNQ4 protein exerted a dominant-negative effect. Interestingly, the channel activity of the p.Leu47Pro KCNQ4 protein was rescued by the KCNQ activators MaxiPost and zinc pyrithione. The c.140T>C (p.Leu47Pro) mutation in KCNQ4 causes progressive NSHL; however, the defective channel activity of the mutant protein can be rescued using channel activators. Hence, in individuals with the c.140T>C mutation, NSHL is potentially treatable, or its progression may be delayed by KCNQ activators.
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http://dx.doi.org/10.1002/humu.23698DOI Listing
March 2019

Therapeutic Effect of Extract in Letrozole-Induced Polycystic Ovary Syndrome Rats.

Front Pharmacol 2018 19;9:1325. Epub 2018 Nov 19.

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.

Polycystic ovary syndrome (PCOS) is an endocrinal disorder that afflicts mainly women of childbearing age. The symptoms of PCOS are irregular menstrual cycles, weight gain, subfertility and infertility. However, because the etiology is unclear, management and treatment methods for PCOS are not well established. Recently, natural substances have been used for PCOS therapy. () is a well-known natural substance that attenuates the effects of inflammation, allergies, and cancer. In this study, we investigated the effects of extract in rats with PCOS. When rats with letrozole-induced PCOS were exposed to the extract, the regular estrus cycle was restored, similar to that in placebo rats. Hormone levels, including the levels of testosterone, estrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH), and anti-Müllerian hormone (AMH), were restored to their normal states. Histological analysis revealed that the polycystic ovary symptoms were significantly decreased in the -treated rats and were comparable to those of normal ovaries. At the transcriptional and translational levels, , and levels were markedly increased in the -treated rats with PCOS compared with the rats with letrozole-induced PCOS. These results suggest that the extract inhibits the symptoms of PCOS by restoring imbalanced hormonal levels and irregular ovarian cycles in letrozole-induced female rats.
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http://dx.doi.org/10.3389/fphar.2018.01325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262357PMC
November 2018

Effectiveness of Morphological Sex Determination in the East Asian Barn Swallow () on Spring Migration.

Zool Stud 2018 15;57:e43. Epub 2018 Oct 15.

Bird Research Center, National Park Research Institute, Korea National Park Service, Jeonnam 58863, Republic of Korea. E-mail: (Nam).

Information on sexual dimorphism helps explain a species' evolution in sexual selection and conservation issues such as sex-specific response in environmental changes. The Barn Swallow () is a well-known sexually dimorphic species in which males have longer tail streamers than females. However, when compared with the European-African or American subspecies, little information is available on morphological sex determination in the East Asian subspecies , especially outside the breeding season, when opportunities for molecular sexing are often limited and morphological clues may be the only ones available for sex determination. We collected morphological data on during the northbound spring migration at a stopover site off the Korean coast. Two of eight measured variables - streamer length (the difference in length between the 5th and 6th rectrices; T6-T5) and length of the white patch on the outermost tail (6th rectrix; T6) - were selected as the best predictors for sex determination by stepwise discriminant analysis. Quadratic discriminant functions based on these variables showed that 92.4-93.5% of females and 82.9% of males were correctly classified. Our results provide baseline information that will benefit more accurate sex determination of the East Asian Barn Swallows, especially during the early months of a calendar year in non-breeding and stopover areas.
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http://dx.doi.org/10.6620/ZS.2018.57-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517734PMC
October 2018

Allogenic Pure Platelet-Rich Plasma Therapy for Rotator Cuff Disease: A Bench and Bed Study.

Am J Sports Med 2018 11 12;46(13):3142-3154. Epub 2018 Oct 12.

Department of Laboratory Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Dongjak-gu, Seoul, Republic of Korea.

Background: Although platelet-rich plasma (PRP) is a popular option for rotator cuff disease, the underlying mechanism of PRP and its clinical indications are unclear. Further, some kinds of PRP might be detrimental to patients. Allogenic PRP prepared through a standardized process and fully characterized could eliminate variations in PRP as well as uncertainties regarding its use in each patient, which could provide clues about its mechanism of action and indications for its use.

Purpose: To assess the effects of pure PRP on tenocytes with or without inflammation in an in vitro study and to evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with rotator cuff disease in a clinical study.

Study Design: Controlled laboratory study and cohort study; Level of evidence, 3.

Methods: For the in vitro study, tenocytes were enzymatically isolated and cultured from patients with rotator cuff tear and treated with or without interleukin 1β (IL-1β) and PRP. Gene expression and protein synthesis of pro- and anti-inflammatory cytokines, enzymes and their inhibitors, matrix synthesis, and cell viability were evaluated. For the clinical study, a total of 17 patients with rotator cuff disease received ultrasonography-guided subacromial PRP injection and were followed for 6 months. Pain, range of motion, muscle strength, shoulder function, and overall satisfaction in patients were compared with the results in a propensity score-matched control group who received corticosteroid (triamcinolone acetonide 40 mg).

Results: PRP induced inflammation in the absence of inflammation and ameliorated inflammation in IL-1β-induced tendinopathic conditions by regulation of cytokines such as IL-1β, cyclooxygenase 2, microsomal prostaglandin E synthase 1, vasoactive intestinal peptide, and downstream matrix metalloproteinases. No general or local adverse events were noted with regard to allogenic PRP injection. Whereas steroid injection showed earlier improvement in some kinds of pain and functional scores, PRP generally showed comparable effects with steroid injection in all clinical outcomes at 6 months.

Conclusion: This study showed that allogenic pure PRP had pleiotropic effects on tenocytes depending on inflammation and that it did not cause adverse events but rather decreased pain and improved shoulder function to a degree comparable with steroid injection in patients with rotator cuff disease.

Clinical Relevance: Allogenic PRP could be a treatment option for rotator cuff disease.
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http://dx.doi.org/10.1177/0363546518800268DOI Listing
November 2018

Thymosin β4 is associated with bone sialoprotein expression via ERK and Smad3 signaling pathways in MDPC-23 odontoblastic cells.

Int J Mol Med 2018 Nov 7;42(5):2881-2890. Epub 2018 Sep 7.

Department of Oral Histology and Developmental Biology, College of Dentistry, Chosun University, Gwangju 61452, Republic of Korea.

Thymosin β4 (Tβ4) regulates the expression of molecules associated with dentinogenesis, including bone sialoprotein (BSP). BSP regulates the initiation of mineralization and the direction of dentin growth. However, the association between Tβ4 signaling and BSP expression in odontoblasts remains unclear. Therefore, the aim of the present study was to investigate Tβ4 mRNA expression in odontoblasts during dentinogenesis and the association between the Tβ4 signaling pathway and BSP expression in MDPC‑23 odontoblastic cells. Expression and localization of Tβ4 mRNA was determined by in situ hybridization during mouse tooth development. The effect of Tβ4 signaling on BSP expression was investigated by reverse transcription polymerase chain reaction, western blot analysis, immunofluorescence and a luciferase reporter assay in the presence or absence of specific inhibitors of mitogen activated protein kinase kinase (PD98059) and mothers against decapentaplegic homolog 3 (Smad3; SIS3) in MDPC‑23 cells. The expression of Tβ4 mRNA in the odontoblast layer was highest at postnatal day 5, known as the advanced bell stage, when odontoblasts actively secrete dentin matrix proteins. Tβ4 increased BSP mRNA and protein levels in MDPC‑23 cells, but this was inhibited by PD98059 or SIS3 treatment. Tβ4 increased levels of phosphorylated (p) extracellular signal‑regulated kinase (ERK)1/2, pSmad3, pβ‑catenin, and runt‑related transcription factor 2 (Runx2) protein, but these effects were inhibited by PD98059 or SIS3. Tβ4 induced the nuclear translocation of Runx2 and pSmad3, while nuclear translocation of β‑catenin was decreased. Tβ4 significantly increased BSP promoter activity, which was decreased by PD98059 or SIS3 treatment. Tβ4 induced BSP expression in MDPC‑23 cells via ERK and Smad3 signaling pathways, suggesting its role as a signaling molecule in odontoblasts for regulating BSP secretion during dentinogenesis.
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http://dx.doi.org/10.3892/ijmm.2018.3865DOI Listing
November 2018

Gut-liver on a chip toward an in vitro model of hepatic steatosis.

Biotechnol Bioeng 2018 11 17;115(11):2817-2827. Epub 2018 Sep 17.

Department of Chemical Engineering, Hongik University, Seoul, Korea.

Hepatic steatosis is a process of abnormal lipid deposition within the liver cells, often caused by excessive alcohol uptake or obesity. A conventional in vitro model for hepatic steatosis uses a liver cell culture, treated with fatty acids and measures accumulation of lipids within the cells. This model does not recapitulate the complex process of absorption and metabolism of digestive lipids. Here, we introduce a gut-liver chip, which mimics the gut absorption and hepatic metabolism in a microfluidic chip. Absorption of fatty acids through gut layer and subsequent deposition within liver cells was demonstrated. Tumor necrosis factor-α, butyrate, and α-lipoic acid were chosen as model molecules that can affect hepatic steatosis via different mechanisms, and their effects were evaluated. Our results suggest that the gut-liver chip can mimic the absorption and accumulation of fatty acids in the gut and the liver.
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http://dx.doi.org/10.1002/bit.26793DOI Listing
November 2018

Sloughing a Precursor Layer to Expose Active Stainless Steel Catalyst for Water Oxidation.

ACS Appl Mater Interfaces 2018 Jul 11;10(29):24499-24507. Epub 2018 Jul 11.

Hydrogen production by water electrolysis has been regarded as a promising approach to wean away from sourcing energy through fossil fuels, as the produced hydrogen gas can be converted to electrical or thermal energy without any harmful byproducts. However, an efficient hydrogen production is restricted by the sluggish oxygen evolution reaction (OER) at the counter anode. Therefore, the development of new OER catalysts with high catalytic activities is crucial for high performance water splitting. Here, we report a novel sloughing method for the fabrication of an efficient OER catalyst on a stainless steel (SS) surface. A chalcogenide (Fe-S) overlayer generated by sulfurization on the SS surface is found to play a critical role as a precursor layer in the formation of an active surface during water oxidation. Interestingly, a newly exposed catalytic layer after sloughing off the Fe-S overlayer has a nanoporous structure with changed elemental composition, resulting in a significant improvement in OER performance with an overpotential value of 267 mV at a current density of 10 mA cm (in 1 M KOH). Our novel method for the preparation of OER catalyst provides an important insight into designing an efficient and stable electrocatalyst for the water splitting community.
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http://dx.doi.org/10.1021/acsami.8b04871DOI Listing
July 2018

Renin-angiotensin-aldosterone inhibition improves right ventricular function: a meta-analysis.

Heart Asia 2018 3;10(1):e010999. Epub 2018 May 3.

Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.

The benefits of inhibiting the renin-angiotensin-aldosterone system (RAAS) are well established for left ventricular dysfunction, but remain unknown for right ventricular (RV) dysfunction. The aim of the current meta-analysis is to investigate the role of RAAS inhibition on RV function in those with or at risk of RV dysfunction. Medline, PubMed, EMBASE and Cochrane Libraries were systematically searched and 12 studies were included for statistical synthesis, comprising 265 RAAS inhibition treatment patients and 265 placebo control patients. The treatment arm showed a trend towards increased RV ejection fraction (weighted mean difference (WMD)=0.95, 95% CI -0.12 to 2.02, p=0.08) compared with the control arm. Subgroup analysis demonstrated a trend towards improvement in RV ejection fraction in patients receiving angiotensin receptor blockers compared with control (WMD=1.11, 95% CI -0.02 to 2.26, p=0.06), but not in the respective comparison for ACE inhibitors (WMD=0.07, 95% CI -2.74 to 2.87, p>0.05). No differences were shown between the two groups with regard to maximal oxygen consumption, RV end-systolic volume, RV end-diastolic volume, duration of cardiopulmonary exercise testing, and resting and maximal heart rate. Mild adverse drug reactions were common but evenly distributed between the treatment and control groups. The current meta-analysis highlights that there may be a role for RAAS inhibition, particularly treatment with angiotensin receptor blockers, in those with or at risk of RV dysfunction. However, further confirmation will be required by larger prospective trials.
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http://dx.doi.org/10.1136/heartasia-2018-010999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950636PMC
May 2018

The Pilot Survey of the Perception on the Practice Pattern, Diagnosis, and Treatment on Korean Medicine Insomnia: Focusing on the Difference between Korean Medical Neuropsychiatry Specialists and Korean Medical General Practitioners.

Evid Based Complement Alternat Med 2018 11;2018:9152705. Epub 2018 Feb 11.

Department of Oriental Neuropsychiatry, College of Oriental Medicine, Dong-Eui University, Busan, Republic of Korea.

Introduction: This study aims to investigate the clinical practice states on the diagnosis and treatment for insomnia between Korean medical general practitioners (KMGPs) and Korean medical neuropsychiatry specialists (KMNPSs).

Methods: We distributed questionnaires via email or in person to 1,017 KMGPs and via email to 165 KMNPSs. We collected and analyzed responses from 305 (30.00%) KMGPs and 53 (32.12%) KMNPSs.

Results: Most KMGPs and KMNPSs responded that the number of new patients visiting the clinic for treatment of insomnia was less than 10 per month (78.2%). Frequently utilized therapies for insomnia are acupuncture and herbal decoctions. Particularly acupoint GV20 and Guipi decoction were chosen with the highest response rate. There was no difference between KMNPSs and KMGPs in the traditional Korean medical diagnosis methods. However, KMNPSs utilized more various methods to diagnose, treat, and evaluate insomnia and educated more actively sleep hygiene compared to KMGPs.

Conclusions: This survey showed how insomnia is currently diagnosed and treated in Korean medical care settings. Moreover, we identified some differences between KMNPSs and KMGPs. Further research is required to explore the underlying reasons for these discrepancies among KMDs and to improve the quality of Korean medical clinical practice in treating insomnia.
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http://dx.doi.org/10.1155/2018/9152705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828562PMC
February 2018
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