PKCε-mediated ERK1/2 activation involved in radiation-induced cell death in NIH3T3 cells

AbstractProtein kinase C (PKC) isoforms play distinct roles in cellular functions. We have previously shown that ionizing radiation activates PKC isoforms (α, δ, ε, and ζ), however, isoform-specific sensitivities to radiation and its exact mechanisms in radiation mediated signal transduction are not fully understood. In this study, we showed that overexpression of PKC isoforms (α, δ, ε, and ζ) increased radiation-induced cell death in NIH3T3 cells and PKCε overexpression was predominantly responsible. In addition, PKCε overexpression increased ERK1/2 activation without altering other MAP-kinases such as p38 MAPK or JNK. Co-transfection of dominant negative PKCε (PKCε-KR) blocked both PKCε-mediated ERK1/2 activation and radiation-induced cell death, while catalytically active PKCε construction augmented these phenomena. When the PKCε overexpressed cells were pretreated with PD98059, MEK inhibitor, radiation-induced cell death was inhibited. Co-transfection of the cells with a mutant of ERK1 or -2 (ERK1-KR or ERK2-KR) also blocked these phenomena, and co-transfection with dominant negative Ras or Raf cDNA revealed that PKCε-mediated ERK1/2 activation was Ras–Raf-dependent. In conclusion, PKCε-mediated ERK1/2 activation was responsible for the radiation-induced cell death

Genetic diversity of Imjin virus in the Ussuri white-toothed shrew (Crocidura lasiura) in the Republic of Korea, 2004-2010

Recently, Imjin virus (MJNV), a genetically distinct hantavirus, was isolated from lung tissues of the Ussuri white-toothed shrew (Crocidura lasiura) captured near the demilitarized zone in the Republic of Korea. To clarify the genetic diversity of MJNV, partial M- and L-segment sequences were amplified from lung tissues of 12 of 37 (32.4%) anti-MJNV IgG antibody-positive Ussuri white-toothed shrews captured between 2004 and 2010. A 531-nucleotide region of the M segment (coordinates 2,255 to 2,785) revealed that the 12 MJNV strains differed by 0-12.2% and 0-2.3% at the nucleotide and amino acid levels, respectively. A similar degree of nucleotide (0.2-11.9%) and amino acid (0-3.8%) difference was found in a 632-nucleotide length of the L segment (coordinates 962 to 1,593) of nine MJNV strains. Phylogenetic analyses, based on the partial M and L segments of MJNV strains generated by the neighbor-joining and maximum likelihood methods, showed geographic-specific clustering, akin to the phylogeography of rodent-borne hantaviruses

Analysis On Runoff Characteristics Of Decentralized Rainwater Management System Using XP-SWMM Simulation

In recent years, impervious areas are increasing in residential zone as well as unsettled area with rapid urbanization and land use. Consequently, this phenomenon influences weak urban environmental compositions about climate change including urban flooding accidents. Therefore, a new paradigm on rainwater management is needed for sound and sustainable restoration of hydrological circulation. Recently, a novel rainwater management system has been developed and recommended for irrigation and flood control in Korea. Especially, P city is now planning a new rainwater management system adopting LID (Low Impact Development) techniques on a small scale development area. In this study, XP-SWMM was used to simulate effects on runoff characteristics by installation of 8 kinds of rainwater management facilities on small scale development area (4.2 ha) of P city in Korea. Also, flood control safety analysis under the condition of localized torrential downpour event was carried out and effects of rainwater recycling facility was evaluated to measure annual water resource amount and water cost reduction. Peak rate runoff was reduced 11.8% and 36.4% in restrict A and B, respectively. Total amount of annual water source substitution was estimated 3,000㎡/yr with LID adoption in land use planning. Acknowledgement : This research was supported by a grant (12-TI-C01) from Advanced Water Management Research Program funded by Ministry of Land , Infrastructure, and Transport of Korean government

Epidemiology of Insomnia in Korean Adults: Prevalence and Associated Factors

Background and Purpose Insomnia is a common complaint in adults. However, large epidemiologic studies of insomnia involving Asian populations are rarely reported. We performed an epidemiologic study of insomnia in a large Korean adult population. Methods A total of 5,000 subjects (2,470 men and 2,530 women) were interviewed by telephone. A representative sample of subjects aged 20 to 69 years was constituted according to a stratified, multistage random sampling method. Insomnia was defined as either any difficulty getting to sleep or getting back to sleep after waking in the night. Results More than one fifth (n=1,141, 22.8%) of the 5,000 subjects complained of insomnia, with the prevalence being significantly higher in women (25.3%) than in men (20.2%, P<0.001). Logistic regression revealed that the prevalence of insomnia increased significantly with age (p<0.001), being higher in those aged 60-69 years than in those aged 20-29 years (OR=2.368, 95% CI=1.762-3.182, p<0.001), and was lower in those with a monthly income of >4.5 million Korean won than in those with an income of <1.5 million Korean won (OR=0.689, 95% CI= 0.523-0.906,p<0.01). Conclusions Insomnia is a common complaint in Korean adults, and its prevalence is similar to that in adults in Western countries. J Clin Neurol 2009;5:20-23This work was supported by the research promoting grant from the Keimyung University Dongsan Medical Center in 2006

Efficacy and safety of ginsam, a vinegar extract from Panax ginseng, in type 2 diabetic patients: Results of a double‐blind, placebo‐controlled study

Abstract Aims/Introduction: The efficacy, dose–response relationship and safety of ginsam, a vinegar extract from Panax ginseng, were evaluated in an 8‐week, double‐blind, randomized, placebo‐controlled study in drug‐naïve patients with type 2 diabetes. Materials and Methods: A total of 72 diabetic patients were randomized to receive 1500, 2000 or 3000 mg of ginsam, or placebo daily for 8 weeks (n = 18 in each group). The primary end‐point was the changes from the baseline HbA1c level. The secondary end‐points were the changes of fasting and postprandial 2‐h glucose concentration, and the proportion of patients achieving a reduction in HbA1c >0.5%. Results: In the intention‐to‐treat analysis, ginsam treatment reduced HbA1c level significantly: −0.56 ± 0.25% in the 1500 mg group, −0.31 ± 0.12% in the 2000 mg group, and −0.29 ± 0.11% in the 3000 mg group (all P 0.5% differed significantly between the placebo group (11.1%) and the 1500 mg (27.8%) and 2000 mg (27.8%) groups. No severe adverse events were observed in any group. Conclusions: An 8‐week treatment with ginsam, a vinegar extract from P. ginseng, moderately improved HbA1c level and was well tolerated in type 2 diabetic patients with inadequate glycemic control. This trial was registered with ClinicalTrial.Gov (no. NCT01008163). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00185.x, 2011

Anthocyanins from Vitis coignetiae

Recently we have demonstrated that anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) have anticancer effects. Here, we investigate the effects of AIMs on cell proliferation and invasion as well as epithelial-mesenchymal transition (EMT) which have been linked to cancer metastasis in human uterine cervical cancer HeLa cells. AIMs inhibited the invasion of HeLa cells in a dose-dependent manner. AIMs inhibited MMP-9 expression in a dose-dependent manner. AIMs inhibited the motility of HeLa cells in a wound healing test. AIMs still suppressed NF-κB activation induced by TNF. AIMs also inhibited EMT in HeLa cells. AIMs suppressed vimentin, N-cadherin, and β-catenin expression and induced E-cadherin. AIMs also suppressed expression of β-catenin and Snail, which was regulated by GSK-3. These effects of AIMs were also limited in the HeLa cells treated with TNF. In conclusion, this study indicates that AIMs have anticancer effects by suppressing NF-κB-regulated genes and EMT, which relates to suppression of IκBα phosphorylation and GSK-3 activity, respectively. However, the effects of AIMs were attenuated in the TNF-high condition

Use of the Clock Drawing Test and the Rey–Osterrieth Complex Figure Test-copy with convolutional neural networks to predict cognitive impairment

Background The Clock Drawing Test (CDT) and Rey–Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. Methods The CDT and RCFT-copy data were obtained from patients aged 60–80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform ( www.colab.research.google.com ) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). Results The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. Conclusions The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.The costs for manuscript publication, design of the study, data management, and writing of the manuscript were supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2017S1A6A3A01078538)

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

BACKGROUND: Concern over phthalates has emerged because of their potential toxicity to humans. OBJECTIVE: We investigated the relationship between the urinary concentrations of phthalate metabolites and children`s intellectual functioning. METHODS: This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuro-psychological tests were obtained from both the children and their mothers. RESULTS: We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 mu g/L [geometric SD (GSD) = 2.2 mu g/L; range, 0.5-445.4], 18.0 mu g/L (GSD = 2.4; range, 0.07-291.1), and 48.9 mu g/L (GSD = 2.2; range, 2.1-1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children`s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables. CONCLUSION: Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.This work was funded by the Eco-Technopia 21 project of Korea Institute of Environmental Science and Technology (091-081-059).Cho SC, 2010, J CHILD PSYCHOL PSYC, V51, P1050, DOI 10.1111/j.1469-7610.2010.02250.xKim BN, 2009, BIOL PSYCHIAT, V66, P958, DOI 10.1016/j.biopsych.2009.07.034Tanida T, 2009, TOXICOL LETT, V189, P40, DOI 10.1016/j.toxlet.2009.04.005Ghisari M, 2009, TOXICOL LETT, V189, P67, DOI 10.1016/j.toxlet.2009.05.004Barnett JH, 2009, AM J PSYCHIAT, V166, P909, DOI 10.1176/appi.ajp.2009.08081251Kim Y, 2009, NEUROTOXICOLOGY, V30, P564, DOI 10.1016/j.neuro.2009.03.012Engel SM, 2009, NEUROTOXICOLOGY, V30, P522, DOI 10.1016/j.neuro.2009.04.001Kamrin MA, 2009, J TOXICOL ENV HEAL B, V12, P157, DOI 10.1080/10937400902729226Brown JS, 2009, SCHIZOPHRENIA BULL, V35, P256, DOI 10.1093/schbul/sbm147Bellinger DC, 2008, NEUROTOXICOLOGY, V29, P828, DOI 10.1016/j.neuro.2008.04.005Wolff MS, 2008, ENVIRON HEALTH PERSP, V116, P1092, DOI 10.1289/ehp.11007van Neerven S, 2008, PROG NEUROBIOL, V85, P433, DOI 10.1016/j.pneurobio.2008.04.006Hatch EE, 2008, ENVIRON HEALTH-GLOB, V7, DOI 10.1186/1476-069X-7-27Zevalkink J, 2008, J GENET PSYCHOL, V169, P72Kolarik B, 2008, ENVIRON HEALTH PERSP, V116, P98, DOI 10.1289/ehp.10498SATHYANARAYANA S, 2008, CURR PROBL PEDIAT AD, V38, P34KHO YL, 2008, J ENV HLTH SCI, V34, P271Huang PC, 2007, HUM REPROD, V22, P2715, DOI 10.1093/humrep/dem205Janjua NR, 2007, ENVIRON SCI TECHNOL, V41, P5564, DOI 10.1021/es0628755Meeker JD, 2007, ENVIRON HEALTH PERSP, V115, P1029, DOI 10.1289/ehp.9852Fromme H, 2007, INT J HYG ENVIR HEAL, V210, P21, DOI 10.1016/j.ijheh.2006.09.005Xu Y, 2007, ARCH TOXICOL, V81, P57, DOI 10.1007/s00204-006-0143-8Pereira C, 2007, ACTA HISTOCHEM, V109, P29, DOI 10.1016/j.acthis.2006.09.008Hauser R, 2006, EPIDEMIOLOGY, V17, P682, DOI 10.1097/01.ede.0000235996.89953.d7Zhu DF, 2006, BRAIN, V129, P2923, DOI 10.1093/brain/awl215Andrade AJM, 2006, TOXICOLOGY, V227, P185, DOI 10.1016/j.tox.2006.07.022Lottrup G, 2006, INT J ANDROL, V29, P172, DOI 10.1111/j.1365-2605.2005.00642.xBreous E, 2005, MOL CELL ENDOCRINOL, V244, P75, DOI 10.1016/j.mce.2005.06.009Wenzel A, 2005, MOL CELL ENDOCRINOL, V244, P63, DOI 10.1016/j.mce.2005.02.008Kato K, 2005, ANAL CHEM, V77, P2985, DOI 10.1021/ac0481248Tanaka T, 2005, FOOD CHEM TOXICOL, V43, P581, DOI 10.1016/j.fct.2005.01.001Duty SM, 2005, HUM REPROD, V20, P604, DOI 10.1093/humrep/deh656Kota BP, 2005, PHARMACOL RES, V51, P85, DOI 10.1016/j.phrs.2004.07.012Hays T, 2005, CARCINOGENESIS, V26, P219, DOI 10.1093/carcin/bgh285Hauser R, 2004, ENVIRON HEALTH PERSP, V112, P1734, DOI 10.1289/ehp.7212Bornehag CG, 2004, ENVIRON HEALTH PERSP, V112, P1393, DOI 10.1289/ehp.7187Ishido M, 2004, J NEUROCHEM, V91, P69, DOI 10.1111/j.1471-4159.2004.02696.xMink PJ, 2004, EPIDEMIOLOGY, V15, P385, DOI 10.1097/01.ede.0000128402.86336.7eBellinger DC, 2004, EPIDEMIOLOGY, V15, P383, DOI 10.1097/01.ede.0000129525.15064.a4Shea KM, 2003, PEDIATRICS, V111, P1467Tanaka T, 2002, FOOD CHEM TOXICOL, V40, P1499, DOI 10.1016/S0278-6915(02)00073-XHoppin JA, 2002, ENVIRON HEALTH PERSP, V110, P515SATTLER JM, 2001, ASSESSMENT CHILDRENRice D, 2000, ENVIRON HEALTH PERSP, V108, P511Bellinger DC, 2000, NEUROTOXICOL TERATOL, V22, P133LIM YR, 2000, KOR J CLIN PSYCHOL, V19, P563Braissant O, 1998, ENDOCRINOLOGY, V139, P2748Peters JM, 1997, CARCINOGENESIS, V18, P2029Baldini IM, 1997, PROG NEURO-PSYCHOPH, V21, P925Roberts RA, 1997, FUND APPL TOXICOL, V38, P107PARK KS, 1996, DEV KEDI WISC INDIVIMONZANI F, 1993, CLIN INVESTIGATOR, V71, P367SILVERSTEIN AB, 1990, J CLIN PSYCHOL, V46, P333HINTON RH, 1986, ENVIRON HEALTH PERSP, V70, P195KIM MK, 1986, SEOUL J PSYCHIAT, V11, P194KAUFMAN AS, 1976, CONTEMP EDUC PSYCHOL, V1, P1801

Current Status of Clinical Diagnosis and Genetic Analysis of Hereditary Hemorrhagic Telangiectasia in South Korea: Multicenter Case Series and a Systematic Review

Purpose Hereditary hemorrhagic telangiectasia (HHT), a rare genetic vascular disorder, has been rarely reported in South Korea. We investigated the current prevalence and presenting patterns of genetically confirmed HHT in South Korea. Materials and Methods We defined HHT patients as those with proven mutations on known HHT-related genes (ENG, ACVRL1, SMAD4, and GDF2) or those fulfilling 3 or 4 of the Curaçao criteria. A computerized systematic search was performed in PubMed and KoreaMed using the following search term: (“hereditary hemorrhagic telangiectasia” AND “Korea”) OR (“Osler-Weber-Rendu” AND “Korea”). We also collected government health insurance data. HHT genetic testing results were collected from three tertiary hospitals in which the genetic tests were performed. We integrated patient data by analyzing each case to obtain the prevalence and presenting pattern of HHT in South Korea. Results We extracted 90 cases from 52 relevant articles from PubMed and KoreaMed. An additional 22 cases were identified from the three Korean tertiary hospitals after excluding seven cases that overlapped with those in the published articles. Finally, 112 HHT patients were identified (41 males and 71 females, aged 4–82 years [mean±standard deviation, 45.3±20.6 years]). The prevalence of HHT in South Korea is about 1 in 500,000, with an almost equal prevalence among men and women. Forty-nine patients underwent genetic testing, of whom 28 had HHT1 (ENG mutation) and 19 had HHT2 (ACVRL1 mutation); the other two patients were negative for ENG, ACVRL1, and SMAD4 mutations. Conclusion The prevalence of HHT is underestimated in Korea. The rate of phenotypic presentation seems to be similar to that found worldwide. Korean health insurance coverage is limited to representative genetic analysis to detect ENG and ACVRL1 mutations. Further genetic analyses to detect HHT3, HHT4, and other forms of HHT should be implemented

Sensitivity, specificity, and predictive value of cardiac symptoms assessed by emergency medical services providers in the diagnosis of acute myocardial infarction: a multi-center observational study

Objective For patients with acute myocardial infarction (AMI), symptoms assessed by emergency medical services (EMS) providers have a critical role in prehospital treatment decisions. The purpose of this study was to evaluate the diagnostic accuracy of EMS provider-assessed cardiac symptoms of AMI. Methods Patients transported by EMS to 4 study hospitals from 2008 to 2012 were included. Using EMS and administrative emergency department databases, patients were stratified according to the presence of EMS-assessed cardiac symptoms and emergency department diagnosis of AMI. Cardiac symptoms were defined as chest pain, dyspnea, palpitations, and syncope. Disproportionate stratified sampling was used, and medical records of sampled patients were reviewed to identify an actual diagnosis of AMI. Using inverse probability weighting, verification bias-corrected diagnostic performance was estimated. Results Overall, 92,353 patients were enrolled in the study. Of these, 13,971 (15.1%) complained of cardiac symptoms to EMS providers. A total of 775 patients were sampled for hospital record review. The sensitivity, specificity, positive predictive value, and negative predictive value of EMS provider-assessed cardiac symptoms for the final diagnosis of AMI was 73.3% (95% confidence interval [CI], 70.8 to 75.7), 85.3% (95% CI, 85.3 to 85.4), 3.9% (95% CI, 3.6 to 4.2), and 99.7% (95% CI, 99.7 to 99.8), respectively. Conclusion We found that EMS provider-assessed cardiac symptoms had moderate sensitivity and high specificity for diagnosis of AMI. EMS policymakers can use these data to evaluate the pertinence of specific prehospital treatment of AMI