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Two new isochromanone derivatives, (3S,4S)-3,8-dihydroxy-6-methoxy-3,4,5-trimethylisochroman-1-one (1) and methyl (S)-8-hydroxy-6-methoxy-5-methyl-4a-(3-oxobutan-2-yl)benzoate (2), together with six known compounds (3‒8) were isolated from the cultures of an endophytic fungus Phoma sp. PF2 obtained from Artemisia princeps. The chemical structures of the isolated compounds were elucidated by interpretation of spectroscopic data (1D, 2D NMR, HRESIMS, and CD) and calculation of ECD. All the isolated compounds (1‒8) showed moderate inhibitory activities on nitric oxide levels in lipopolysaccharide-induced RAW264.7 machrophage cells.

Objective: To determine the 30-day morbidity rate after hysterectomy for benign disease and identify predictors of 30-day morbidity., Methods: A retrospective study was conducted among women undergoing hysterectomy for benign indications between January 1, 2010, and December 31, 2015, at Konkuk University Hospital, South Korea. Multivariable regression analysis identified independent factors for morbidity., Results: 1609 women were included. 30-day morbidity rates were 4.5% (n=72) for the whole cohort: 7.5% (28/371), 3.2% (22/686), and 4.0% (22/552) for abdominal hysterectomy, laparoscopic-assisted vaginal hysterectomy (LAVH), and vaginal hysterectomy, respectively. The most common 30-day postoperative morbidities were urinary complications (1.2%, 20/1609), wound infection (0.9%, 14/1609), and blood transfusion more than 4 units (0.7%, 11/1609). In multivariate regression analysis, Charlson comorbidity index of 2 or more, operative time, and estimated blood loss were independently associated with morbidity. Propensity score-matching indicated no difference in morbidity rates for the abdominal hysterectomy and LAVH or vaginal hysterectomy groups (P=0.351), whereas the LAVH or vaginal hysterectomy groups were more strongly associated with operation time, estimated blood loss, and length of postoperative hospital stay., Conclusion: Comorbidity index, operative time, and blood loss were independently associated with morbidity following hysterectomy. These findings supported the preoperative optimization of comorbidities and the appropriate selection of surgical approaches., (© 2018 International Federation of Gynecology and Obstetrics.)

Roots of Glehnia littoralis have been used to heal stroke as a traditional medicine. Even though many studies on this plant have been conducted, the secondary metabolites produced by its endophytes and their bioactivities have not been investigated thus far. Therefore, a new meroditerpenoid named sartorypyrone E (1) and eight known compounds (2-9) were isolated from extracts of cultured Neosartorya fischeri JS0553, an endophyte of G. littoralis. The isolated metabolites were identified using spectroscopic methods and chemical reaction, based on a comparison to literature data. Relative and absolute stereochemistries of compound 1 were also elucidated. To identify the protective effects of isolated compounds (1-9) in HT22 cells against glutamate-induced cytotoxicity, we assessed inhibition of cell death, intracellular reactive oxygen species (ROS) accumulation, and calcium ion (Ca 2+ ) influx. Among the isolates, compound 8, identified as fischerin, showed significant neuroprotective activity on glutamate-mediated HT22 cell death through inhibition of ROS, Ca 2+ influx, and phosphorylation of mitogen-activated protein kinase, including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38. The results suggested that the metabolites produced by the endophyte N. fischeri JS0553 might be related to the neuroprotective activity of its host plant, G. littoralis.

Background: Despite heterogeneity of older people in suicidal behavior, research identifying characteristics by age groups is scarce. We examined baseline features of older community-dwelling suicidal ideators by dichotomized age groups and the 6-month trajectory of their suicidal ideation along with its related psychopathology. Predictors of suicidal ideation within each group were investigated., Methods: Older community-dwelling suicidal ideators enrolled in the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior study were subdivided into the "young-old (65-74 years)" and "old-old (≥75 years)" group. Baseline, 1-, and 6-month assessments were compared. Within each group, multiple regression analysis using rating scales (Patient Health Questionnaire-9, Beck Anxiety Inventory, Alcohol Use Disorders Identification Test, Stress Questionnaire for Korean National Health and Nutrition Examination Survey-Short Form, and Social Relationships Scale) was conducted to identify predictors of suicidal ideation measured with the intensity subscale of the Columbia-Suicide Severity Rating Scale. Two-way repeated-measures analysis of variance (RM-ANOVA) was used to compare changes in suicidal ideation, depression, anxiety between age groups over time, and one-way RM-ANOVA to examine changes within each age group., Results: Among 29 "young-old" and 53 "old-old" ideators, the latter were less likely to be receiving psychiatric treatment (odds ratio [OR] = 4.065) and make suicide attempts (OR = 2.874), whereas the former revealed greater levels of anxiety and stress. Baseline depression and stress in the "young-old" group and the "old-old" group, respectively, predicted the intensity of suicidal ideation at both baseline and 1-month assessments. No significant age group x time interactions on suicidal ideation and depression were found. However, within each age group, both suicidal ideation and depression significantly decreased only during the first month with no further improvement., Conclusion: We speculate cautiously that more attention may need to be paid to the "old-old" ideators in the evaluation of psychiatric issues and for referral to psychiatrists. To decrease suicidal ideation, tailored approaches involving proactive, timely management of depression in the "young-old" and interventions focusing on stress reduction in the "old-old," would be helpful., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Hormonal management is an alternative treatment for preserving fertility in patients with presumed early stage endometrioid endometrial cancer. This study aimed to define the pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer., Methods: We retrospectively analyzed patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer who underwent fertility-sparing treatment. Concurrent medroxyprogesterone and levonorgestrel-release intra-uterine devices were used for treatment. The pregnancy outcomes and oncologic outcomes were compared between the pregnant and non-pregnant groups., Results: Seventy-one patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer had complete remission, and 49 of them tried to conceive. Twenty-two (44.9%) patients became pregnant; the total number of pregnancies was 30. These pregnancies resulted in seven abortions (23.3%), one pre-term birth (3.3%), and 20 full-term births (66.6%). The total live birth rate was 66.6 % (20/30). The median duration of hormonal treatment was 11.9 months (range 4-49) and 12.0 months (range 3-35) in the pregnant and non-pregnant groups, respectively. On multivariate analysis, age, body mass index, treatment duration, medroxyprogesterone dose, and number of dilatation and curettage biopsies were not significantly associated with pregnancy failure, but the association with grade (OR 6.2, 95% CI 1.0 to 38.9; P<0.05) was statistically significant. The median disease-free survival duration was 26 months (range 20-38) and 12 months (range 4-48) in the pregnant and non-pregnant groups, respectively (P<0.05, log-rank test)., Conclusions: A lower grade might be a positive factor for future pregnancy. Moreover, successful pregnancy might be a factor in preventing recurrence., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Preeclampsia (PE) is a disorder specific to pregnancy characterized by new-onset hypertension and proteinuria after 20 weeks of gestation. There is no definite treatment for PE except delivery of the placenta. The purpose of this study was to elucidate the biological pathways involved in the development of PE and to discover a novel biomarker for PE by performing global gene expression analysis of amniotic fluid cell-free RNA.The participants were recruited from the Department of Obstetrics and Gynecology of CHA Gangnam Medical Center (Seoul, Korea) between March 2014 and February 2015. Eight samples were collected from 8 subjects at second trimester who were later diagnosed with PE. From the amniotic fluid samples, cell-free RNA extraction was performed and gene expression was analyzed using the GeneChip PrimeView Array. Transcriptome data previously analyzed by our group from 9 euploid mid-trimester amniotic fluid samples were used as the control for comparative analysis. Functional analysis of the probe sets was performed using the online Database for Annotation, Visualization, and Integrated Discovery (DAVID) toolkit 6.7.We identified 1841 differentially expressed genes (DEGs) between the PE group and the control. Of these, 1557 genes were upregulated in the PE group, while 284 genes were upregulated in the control. The functional annotation of DEGs identified specific enriched functions such as "transport," "signal transduction," and "stress response." Functional annotation clustering with enriched genes in the PE group revealed that translation-related genes, cell-cell adhesion genes, and immune-related genes were enriched. KEGG pathway analysis showed that several biological pathways, including the ribosome pathway and various immune pathways, were dysregulated. Several genes, including RPS29, IGF-2, and UBC, were significantly upregulated in PE, up to tenfold.This study provides the first genome-wide expression analysis of amniotic fluid cell-free RNA in PE. The results showed that gene expression involving the ribosome pathway and immunologic pathways are dysregulated in PE. Our results will aid in understanding the underlying pathogenesis of PE.

Purpose: To investigate genetic mutations in Korean patients with Stargardt disease (STGD) using exome sequencing, and to analyze the correlations between genetic mutations and clinical phenotypes., Methods: Peripheral venous blood was obtained from 24 clinically diagnosed Korean STGD patients, followed by extraction of genomic DNAs. Using exome sequencing we investigated gene mutations for the adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) elongation of very-long-chain fatty acids 4 (ELOVL4), and prominin 1 (PROM1), and confirmed gene mutations by the direct sequencing of polymerase chain reaction products., Results: ABCA4 mutations were confirmed in 17 of 24 patients, and 12 novel mutations were identified. ELOVL4 and PROM1 gene mutations were not identified in this study. We also identified 16 previously reported mutations related to STGD1. In patients whose disease symptoms occurred before 20 years of age, visual acuity was poorer and atrophic flecks were more frequently found. In addition, more ABCA4 mutations were found in patients who had choroidal silence or atrophic flecks., Conclusions: Novel ABCA4 gene mutations were found in Korean patients with STGD1. This study will facilitate better understanding of the relationships between ABCA4 gene mutations and clinical symptoms in Korean patients., (© 2018 S. Karger AG, Basel.)

Background: The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS) study is a prospective, naturalistic, observational cohort study, aiming to identify predictors of suicide attempt and suicide characteristics in the Korean suicidal population. The findings intend to contribute to a thorough understanding of suicidal phenomena and development of suicide prevention guidelines. The present cross-section study examines the study rationale, methodology, and baseline characteristics of the participants., Methods: Participants were enrolled via the hospital and community gateways, establishing the hospital-based cohort (HC) and community-based cohort (CC), respectively. Baseline assessment was conducted on sociodemographic, clinical, diagnostic, and psychopathological aspects. The Columbia-Suicide Severity Rating Scale was used to investigate suicidality., Results: A total of 800 suicidal people aged 15 years or older were enrolled from 8 university hospitals and 8 community mental health welfare centers (CMHWCs), among whom 480 (60%) were suicidal ideators and 320 (40%) were attempters. The ideators comprised 207 CC and 273 HC participants, whereas the attempters, 34 CC and 286 HC participants. Despite their lower severity in some measures, including suicidal ideation, compared with their HC counterparts, the CC participants within each group of ideators or attempters presented clinically significant psychopathology. Moreover, alcohol use problems and past suicide attempt were more likely to be found in CC participants. Only 11.1% to 21.6% of the participants in each of the four groups (defined by the cohorts and the ideators/attempters) were on any type of psychiatric treatment., Conclusions: Suicidal visitors to CMHWCs need to be as closely monitored as suicidal patients in university hospitals, especially considering their association with problem drinking and past suicide attempt. A cautious assumption is that the high suicide rate in Korea might be partly attributable to the low proportion of patients receiving psychiatric services., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the incidence and trends of cervical (C53), endometrial (C54.1), and ovarian cancer (C56) among Korean females between 1999 and 2015., Methods: The incidence of the three major gynecological cancers between 1999 and 2015 was analyzed based on the data from the Korea Central Cancer Registry. The age-standardized rates (ASRs) and the annual percent changes (APCs) for each site were calculated., Results: The absolute incidence rates of the three major gynecological cancers increased from 6,394 in 1999 to 8,288 in 2015. ASR for gynecologic cancer decreased from 23.7 per 100,000 in 1999 to 21.1 in 2015. This was mainly due to a definitive decrease in the incidence of cervical cancer, which recorded an APC of -3.7%. The trends of APC for gynecologic cancer were variable, being -1.36% between 1999 and 2006 and -0.11% between 2006 and 2015. A definitive but variable increase was noted for endometrial cancer, and the APC for this cancer was 7.4% between 1999 and 2009 and 3.5% between 2009 and 2015. The incidence of ovarian cancer gradually increased, with an APC of 1.8% between 1999 and 2015., Conclusion: Overall, ASRs and APCs for the three major gynecological cancers are decreasing, with a recent reduction in the width of the change. However, there has been a progressive increase in the incidence of endometrial and ovarian cancers., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objective: The aim of this study was to evaluate differences in psychopathology between offspring of parents with bipolar I disorder (BP-I) and those with bipolar II disorder (BP-II)., Methods: The sample included 201 offspring between 6 and 17 years of age who had at least one parent with BP-I or BP-II. The offspring were diagnostically evaluated using the Korean Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. Psychopathology and Clinical characteristics were evaluated, including lifetime DSM-5 diagnoses, depression, and childhood trauma. Lifetime DSM-5 diagnoses were also compared between schoolchildren aged 6 to 11 years and adolescents aged 12 to 17 years., Results: In lifetime DSM-5 diagnoses, offspring of parents with BP-I had significantly increased risk of developing MDD and BP-I than those with BP-II. Regarding clinical characteristics, ADHD rating scale and childhood trauma scale were significantly higher in offspring of parents with BP-I than that in those with BP-II., Conclusion: The present study supports that BP-I may be etiologically distinct from BP-II by a possible genetic liability. Our findings indicate that additional research related to bipolar offspring is needed to enhance understanding of differences between BP-I and BP-II.

In this study, we aimed to investigate associations between polymorphisms of folate metabolic pathway genes and unexplained pregnancy loss (UPL) using matched maternal-fetal samples. A total of 113 mother-abortus and 92 mother-newborn samples were collected. Among the 113 mother-abortus samples, 50 with chromosomal abnormality and 22 with maternal cell contamination were excluded. Samples were genotyped for RFC-1 80A>G, MTHFD1 1958 G>A, MTHFR 677C>T, and MTHFR 1298A>C polymorphisms using restriction fragment length polymorphism markers. The genotypes of RFC-1 80A>G, MTHFD1 1958 G>A, MTHFR 677C>T, and MTHFR 1298A>C were not associated with UPL in maternal samples. In the fetal samples, the frequency of heterozygous genotype (GA) of MTHFD11958 G>A was significantly higher than that that of the control (OR = 2.477, 95% CI = 1.128-5.446, p = 0.037). The AA-GA genotypes of MTHFD1 1958G>A and RFC-1 80A>G were significantly higher in mother-abortus samples (p = 0.016) than in the mother-newborn samples (p = 0.029). Frequencies of allelic combinations of MTHFR 677C>T/MTHFD11958G>A and RFC-1 80A>G/MTHFR677C>T/MTHFD1 1958G>A were significantly higher in maternal samples of the UPL group. In the fetal samples, no significant differences were detected between the UPL group and the control group. This study is the first to show associations between MTHFD1 1958G>A, RFC-1 80G>A, MTHFR 677C>T, and MTHFR 1298A>C polymorphisms and UPL and to compare the effects of maternal and fetal samples on UPL using mother-abortus matched samples of Korean origin., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was first published in 2002 through an expert consensus of opinion, and updated in 2006, 2010, and 2014. This study constitutes the fourth revision of the KMAP-BP., Methods: A 50-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of adult bipolar disorder and six items for pediatric bipolar disorder. The review committee included 84 Korean psychiatrists and 43 child and adolescent psychiatry experts., Results: The preferred first-step strategies for acute mania were the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. A combination of a MS and an AAP, and AAP monotherapy were preferred for psychotic mania. The first-step strategies for mild to moderate bipolar depression were monotherapy with MS, AAP, or lamotrigine (LMT), and the combination of a MS and an AAP or LMT, or a combination of an AAP and LMT. The combination of two among a MS, AAP, and LMT were preferred for non-psychotic severe depression. A combination of a MS and an AAP or the combination of an AAP with an antidepressant or LMT were the first-line options for psychotic severe depression., Conclusion: The recommendations of the KMAP-BP 2018 have changed from the previous version by reflecting recent developments in pharmacotherapy for bipolar disorder. KMAP-BP 2018 provides clinicians with a wealth of information regarding appropriate strategies for treating patients with bipolar disorder.

Background: For many years, researchers have sought to overcome major challenges in the use of nanoparticles as therapeutics, including issues related to intracellular delivery, biocompatibility, and activation. In particular, the genetic stability of cells treated with nanoparticles has become increasingly important in the context of stem cell therapy. Methods: Functional nanoparticles (Sunflower typed nanoparticles; SF-NPs) were fabricated by coating heparin pluronic F127 gels with quantum dot nanoparticles (QDs), and then bound the SOX9 gene to the QD nanogels. The resultant nanoparticles were transferred into stem cells, and the effect on genetic stability was monitored. To determinate gene delivery efficacy and long-term genomic stability of cells transfected with QD nanogels, hMSCs were transfected with nanogels at passage 4 (T1; Transfected cells 1) and then sub-cultured to passage of (T4). Following transplantation of transfected T1-T4 cells, the cells were monitored by in vivo imaging. The genetic stability of cells treated with nanoparticles was confirmed by chromosomal analysis, copy number variation (CNV) analysis, and mRNA profiling. Results: After 21 days of pellet culture after sub-culture from T1 to T4, hMSCs treated with QD nanogels complexed with SOX9 plasmid DNA (pDNA) significantly increased expression of specific extracellular matrix (ECM) polysaccharides and glycoproteins, as determined by Safranin O and Alcian blue staining. Moreover, the T4 hMSCs expressed higher levels of specific proteins, including collagen type II (COLII) and SOX9, than P4 hMSCs, with no evidence of DNA damage or genomic malfunction. Microarray analysis confirmed expression of genes specific to matured chondrocytes. Stem cells that internalized nanoparticles at the early stage retained genetic stability, even after passage. In in vivo studies in rats, neuronal cartilage formation was observed in damaged lesions 6 weeks after transplantation of T1 and T4 cells. The degree of differentiation into chondrocytes in the cartilage defect area, as determined by mRNA and protein expression of COLII and SOX9, was higher in rats treated with SF-NPs. Conclusion: The QD nanogels used in this study, did not affect genome integrity during long-term subculture, and are thus suitable for multiple theranostic applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Triple negative breast cancer (TNBC) is aggressive with a worse prognosis. We have recently shown that bitter melon extract (BME) treatment was more effective in inhibition of TNBC tumor growth in mouse models as compared to ER positive breast tumor growth. Aberrant dysregulation of lipid metabolism is associated with breast cancer progression, however, anti-cancer mechanism of BME linking lipid metabolism in breast cancer growth remains unexplored. Here, we observed that accumulation of esterified cholesterol was reduced in BME treated TNBC cell lines as compared to control cells. We next evaluated expression levels of acyl-CoA: cholesterol acyltransferase 1 (ACAT-1) in TNBC cells treated with BME. Our results demonstrated that BME treatment inhibited ACAT-1 expression in TNBC cells. Subsequently, we found that sterol regulatory element-binding proteins-1 and -2, and FASN was significantly reduced in BME treated TNBC cell lines. Low-density lipoprotein receptor was also downregulated in BME treated TNBC cells as compared to control cells. We further demonstrated that BME feeding reduced tumor growth in TNBC mammospheres implanted into NSG mice, and inhibits ACAT-1 expression. To our knowledge, this is the first report demonstrating BME suppresses TNBC cell growth through ACAT-1 inhibition, and have potential for additional therapeutic regimen against human breast cancer., (© 2018 Wiley Periodicals, Inc.)

Nano-sized particles (NPs) of various materials have been extensively used as therapeutic and diagnostic agents, drug delivery systems, and biomedical devices. However, the biological impacts of NP exposure during early embryogenesis on following development and next generations have not been investigated. Here, we demonstrated that polylactic-co-glycolic acid (PLGA)-NPs were not toxic and did not perturb development of preimplantation mouse embryos in vitro. Moreover, subsequent fetal development in vivo after embryo transfer proceeded normally and healthy pups were born without any genetic aberrations, suggesting biosafety of PLGA-NPs during developmental processes. TRITC-labeled PLGA-NPs, named TRITC nano-tracer (TnT) were used to visualize the successful delivery of the NPs into sperms, oocytes and early embryos. Various molecular markers for early embryogenesis demonstrated that TnT treatment at various developmental stages did not compromise embryo development to the blastocyst. mRNA-Seq analyses reinforced that TnT treatment did not significantly affect mRNA landscapes of blastocysts which undergo embryo implantation critical for following developmental processes. Moreover, when 2-cell embryos exposed to TnT were transferred into pseudopregnant recipients, healthy offspring were born without any distinct morphologic and chromosomal abnormalities. TnT treatment did not affect the sex ratio of the exposed embryos after birth. When mated with male mice, female mice that were exposed to TnT during early embryogenesis produced a comparable number of pups as control females. Furthermore, the phenotypes of the offspring of mice experienced TnT at their early life clearly demonstrated that TnT did not elicit any negative transgenerational effects on mammalian development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

There is a paucity of research characterizing suicide-related factors in victims of early trauma (ET). This cross-sectional study investigated an increase in trait impulsivity of ET victims with suicidal ideation or behavior and its role in severity of psychopathologies and experienced stress. Using data of 401 Korean suicidal ideators and attempters, trait impulsivity, severity of psychopathologies, and stress levels in addition to sociodemographic and clinical characteristics were compared between the ET group and the no ET group. Three first-order factors of trait impulsivity measured in Barratt Impulsive Scale-11 (cognitive instability, motor, and [lack of] perseverance) as well as depression, anxiety, overall stress level, and stress from social relationships were significantly elevated in the ET group. Owing to the long-lasting neurobiological influences of ET, it is recommended clinically that victims be carefully monitored for the development of mental distress, such as depression and anxiety, even in adulthood.

Fluorescent proteins contain an internal chromophore constituted of amino acids or an external chromophore covalently bonded to the protein. To increase their fluorescence intensities, many research groups have attempted to mutate amino acids within or near the chromophore. Recently, a new type of fluorescent protein, called UnaG, in which the ligand binds to the protein through many noncovalent interactions was discovered. Later, a series of mutants of the UnaG protein were introduced, which include eUnaG with valine 2 mutated to leucine emitting significantly stronger fluorescence than the wild type and V2T mutant, in which valine 2 is mutated to threonine, emitting weaker fluorescence than the wild type. Interestingly, the single mutation sites of both eUnaG and V2T mutants are distant from the fluorophore, bilirubin, which renders the mechanism of such fluorescence enhancement or reduction unclear. To elucidate the origin of fluorescence intensity changes induced by the single mutations, we carried out extensive analyses on MD simulations for the original UnaG, eUnaG and V2T, and found that the bilirubin ligand bound to eUnaG is conformationally more rigid than the wild-type, particularly in the skeletal dihedral angles, possibly resulting in the increase of quantum yield through a reduction of non-radiative decay. On the other hand, the bilirubin bound to the V2T appears to be flexible than that in the UnaG. Furthermore, examining the structural correlations between the ligand and proteins, we found evidence that the bilirubin ligand is encapsulated in different environments composed of protein residues and water molecules that increase or decrease the stability of the ligand. The changed protein stability affects the mobility and confinement of water molecules captured between bilirubin and the protein. Since the flexible ligand contains multiple hydrogen bond (H-bond) donors and acceptors, the H-bonding structure and dynamics of bound water molecules are highly correlated with the rigidity of the bound ligand. Our results suggest that, to understand the fluorescence properties of protein mutants, especially the ones with noncovalently bound fluorophores with internal rotations, the interaction network among protein residues, ligand, and water molecules within the binding cavity should be investigated rather than focusing on the local structure near the fluorescing moiety. Our in-depth simulation study may offer a foundation for the design principles for engineering this new class of fluorescent proteins.

Although autologous induced pluripotent stem cells (iPSCs) can potentially be useful for treating patients without immune rejection, in reality it will be extremely expensive and labor-intensive to make iPSCs to realize personalized medicine. An alternative approach is to make use of human leukocyte antigen (HLA) haplotype homozygous donors to provide HLA matched iPSC products to significant numbers of patients. To establish a haplobank of iPSCs, we repurposed the cord blood bank by screening ∼4,200 high resolution HLA typed cord blood samples, and selected those homozygous for the 10 most frequent HLA-A,-B,-DRB1 haplotypes in the Korean population. Following the generation of 10 iPSC lines, we conducted a comprehensive characterization, including morphology, expression of pluripotent markers and cell surface antigens, three-germ layer formation, vector clearance, mycoplasma/microbiological/viral contamination, endotoxin, and short tandem repeat (STR) assays. Various genomic analyses using microarray and comparative genomic hybridization (aCGH)-based single nucleotide polymorphism (SNP) and copy number variation (CNV) were also conducted. These 10 HLA-homozygous iPSC lines match 41.07% of the Korean population. Comparative analysis of HLA population data shows that they are also of use in other Asian populations, such as Japan, with some limited utility in ethnically diverse populations, such as the UK. Taken together, the generation of the 10 most frequent Korean HLA-homozygous iPSC lines serves as a useful pointer for the development of optimal methods for iPSC generation and quality control and indicates the benefits and limitations of collaborative HLA driven selection of donors for future stocking of worldwide iPSC haplobanks. Stem Cells 2018;36:1552-1566., (© 2018 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background: Lespedeza cuneata G.Don (LCE), which belongs to the genus Lespedeza (Leguminosae), is a traditional oriental medicine known to prevent diabetes and cardiovascular diseases. However, no scientific studies about the effectiveness of LCE, their responsible bioactive constituents, and its mechanisms against endothelial dysfunction have been performed., Purpose: This study was performed to investigate the role of LCE and its chemical components in ameliorating endothelial dysfunction., Methods: The production of nitric oxide (NO) was evaluated after LCE treatment in HUVECs. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Western blot analysis was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) and protein kinase B (PKB, also known as Akt) in human umbilical vein endothelial cells (HUVECs)., Results: Pretreatment with L-NAME and LY294002 significantly decreased the LCE-induced NO production, as well as eNOS and Akt phosphorylation. β-Sitosterol and β-Sitosterol 6'-linolenoyl-3-O-β-D-glucopyranoside are the bioactive constituents increase NO production as well as eNOS phosphorylation., Conclusion: Our findings suggest that LCE increase NO production via eNOS phosphorylation of PI3K/Akt signaling pathway., (Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: This study aimed to evaluate the validity and reliability of a Korean version of the Mood Disorder Questionnaire-Adolescent version (K-MDQ-A) as a screening instrument for bipolar disorders in adolescents., Methods: One hundred two adolescents with bipolar disorders and their parents were recruited from November 2014 to November 2016 at 7 training hospitals. One hundred six controls were recruited from each middle school in two cities of South Korea. The parent version of the original MDQ-A was translated into Korean. The parents of all participants completed the K-MDQ-A. The diagnoses of bipolar disorders were determined based on the Korean version of K-SADS-PL. The test-retest reliability with a 10-month interval was investigated in 33 bipolar adolescents., Results: K-MDQ-A yielded a sensitivity of 0.90 and a specificity of 0.92 when using a cut-off score of endorsement of 5 items, indicating that symptoms occurred in the same time period and caused moderate or serious problems. The internal consistency of the K-MDQ-A was good. The correlations between each item and the total score ranged from 0.40 to 0.76 and were all statistically significant. Factor analysis revealed 3 factors that explained 61.25% of the total variance. The mean total score was significantly higher in bipolar adolescents (7.29) than in controls (1.32). The Pearson correlation coefficient for the total test-retest score was 0.59 ( p ＜0.001)., Conclusion: The K-MDQ-A completed by parents showed the excellent validity and reliability and may be a useful screening tool for adolescents with bipolar disorders attending in- and outpatient psychiatric clinics.

Background: Sjogren-Larsson syndrome is a hereditary neurocutaneous syndrome that is non-progressive in nature. Although neuroregression has been reported in seizure-prone preschool children requiring anti-epileptic treatment, teenage-onset dystonia precipitating neurodegeneration without any immediate causal events has yet to be reported., Case Presentation: We describe a young woman with spastic diplegia and intellectual disability who began to show progressive neurological deterioration from 12 years of age, with the onset of dystonia and tremor. She was initially diagnosed with spastic cerebral palsy and periventricular leukomalacia based on brain magnetic resonance imaging. Follow-up brain imaging from 13 years of age did not reveal apparent changes, though abnormal electroencephalographic findings occurred in parallel with her decline in motor function. By 19 years of age, she had developed dysphagia and became completely dependent on others for most activities of daily living. Ultimately, whole-exome sequencing revealed a heterozygous compound mutation in the ALDH3A2 gene that corresponds to Sjogren-Larsson syndrome: an exon 9 deletion (1291-1292delAA) from the mother and an exon 5 splicing mutation (798 + 1delG) from the father. Neuroregression has been reported in preschool children after seizures requiring treatment, though our patient did not experience any immediate causal events. This report summarizes the clinical, radiologic, and electrophysiological findings observed over a decade concurrent with neurological deterioration after the onset of dystonia and tremor at the age of developmental ceiling in Sjogren-Larsson syndrome., Conclusions: In addition to the influence of additive variants or other environmental factors, accumulation of metabolites due to defective fatty aldehyde dehydrogenase is a potential pathomechanism of neurodegeneration in this patient. Neurological deterioration may be a presentation that is unnoticed in Sjogren-Larsson syndrome due to the rarity of the disease. This report highlights a unique clinical feature of Sjogren-Larsson syndrome with progressive neurodegeneration associated with dystonia and tremor.

Sparassis crispa (Wulf.) belonging to the family of Sparassidaceae, has been widely used as an edible mushroom due to its unique flavor and functions to improve health. In this study, the compounds isolated from the extract of this mushroom were simultaneously quantified by the developed HPLC-DAD method and evaluated for the inhibitory activities on the production of the LPS-stimulated cytokines (IL-12p40, IL-6, and TNF-α) in bone marrow-derived dendritic cells (BMDCs). The contents of this compounds were 0.1928 ± 0.0118, 4.4137 ± 0.0240, 0.5237 ± 0.0005, 2.7303 ± 0.0206 mg/g for sparoside A (1), methyl 2,4-dihydroxy-3-methoxy-6-methylbenzoate (2), sparalide A (3), and 5'-deoxy-5'-methylthioadenosine (4), respectively, which demonstrated that they are the major constituents of this mushroom. Thus, our results were found that the sparoside A (1), 5-hydroxy-7-methoxyphthalide (6), 5-methoxy-7-hydroxyphthalide (7), nicotinamide (10), and adenosine (11) inhibit LPS-stimualted cytokine production, compound 6 is the most potent inhibitory activities on the production of IL-12p40, IL-6, and TNF-α with IC 50 values of 0.19, 0.18, and 0.91 μM, respectively.

Apios americana is an important food crop producing edible tubers with high nutritional and medicinal values and is widely cultivated in many countries. Despite its usefulness, research on its secondary metabolites and biological activities has been limited. In the present study, a new coumaronochromone, (2 R,3 S)-3,7,4'-trihydroxy-5-methoxycoumaronochromone (1), and two new isoflavone glucosides, 7,2',4'-trihydroxy-5-methoxyisoflavone-4'- O-β-d-glucopyranoside (3) and 5,7,4'-trihydroxyisoflavone-7- O-β-d-gentiotrioside (5), were isolated from the tubers of A. americana via chromatographic separation. Seventeen known compounds (2, 4, and 6-20) were also obtained from this plant part. The chemical structures of 1, 3, and 5 were determined by the interpretation of spectroscopic data. The absolute structure of the new compound 1 was established from experimental and calculated electronic circular dichroism spectra. This is the first study to determine the absolute configuration of a 3-hydroxycoumaronochromone derivative. The potential anti-inflammatory activity of the 20 isolates obtained was evaluated by measuring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Among the isolates, seven compounds (1, 3, 6-8, 15, and 20) showed substantial inhibition of nitric oxide production in RAW 264.7 cells, with the most active being compound 1 (IC 50 value of 0.38 ± 0.04 μM).

Objective: To estimate the effect of adjuvant chemotherapy (AC) on the prognosis in cervical cancer patients with intermediate- or high-risk factors after radical hysterectomy (RH) compared to that for adjuvant radiotherapy (AR)., Methods: The Embase and MEDLINE databases and the Cochrane Library were searched for published studies comparing cervical cancer patients who received AC with those who received AR after RH. The endpoints were patient oncologic outcome. Random-effects meta-analytical models were used to calculate the pooled estimates of the effect of AC on mortality/recurrence., Results: Two randomized trials and eleven observational studies (AC, 942 patients; AR, 1,721 patients) met our search criteria. There were no significant differences in mortality and any recurrence between two groups. The results for distant recurrence favored the AC group (pooled odds ratio: 0.69; 95% confidence interval: 0.54-0.88; p=0.03). In subgroup analyses (for study design, histology, indication for adjuvant treatment, AR type, AC type, and lymph node metastasis), there was no significant increase in mortality and recurrence for AC compared with that for AR., Conclusion: Compared to AR, AC showed similar survival outcomes in cervical cancer patients undergoing RH and also appeared to reduce the risk of distant recurrence., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Coherent Raman scattering spectroscopy and microscopy are useful methods for studying the chemical and biological structures of molecules with Raman-active modes. In particular, coherent anti-Stokes Raman scattering (CARS) microscopy, which is a label-free method capable of imaging structures by displaying the vibrational contrast of the molecules, has been widely used. However, the lack of a technique for switching-off the CARS signal has prevented the development of the super-resolution Raman imaging method. Here, we demonstrate that a selective suppression of the CARS signal is possible by using a three-beam double stimulated Raman scattering (SRS) scheme; the three beams are the pump, Stokes, and depletion lights in order of frequency. Both pump-Stokes and pump-depletion beam pairs can generate SRS processes by tuning their beat frequencies to match two different vibrational modes, then two CARS signals induced by pump-Stokes-pump and pump-depletion-pump interactions can be generated, where the two CARS signals are coupled with each other because they both involve interactions with the common pump beam. Herein, we show that as the intensity of the depletion beam is increased, one can selectively suppress the pump-Stokes-pump CARS signal because the pump-depletion SRS depletes the pump photons. A detailed theoretical description of the coupled differential equations for the three incident fields and the generated CARS signal fields is presented. Taking benzene as a molecular system, we obtained a maximum CARS suppression efficiency of about 97% with our experimental scheme, where the ring breathing mode of the benzene is associated with pump-Stokes-pump CARS, while the C-H stretching mode is associated with the competing pump-depletion SRS process. We anticipate that this selective switching-off scheme will be of use in developing super-resolution label-free CARS microscopy.

Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca 2+ influx triggered by glutamate. Immunoblot analysis revealed that compound 4 reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4 strongly attenuated glutamate-mediated apoptotic cell death.

Background and Objective: Evidence shows that a short stature in adulthood is associated with chronic diseases. However, few studies have investigated the association between height and periodontitis. The purpose of this study was to examine the relationship between adult height and periodontitis and to assess the roles of covariates in different birth cohorts of Korea., Material and Methods: This was a cross-sectional study using the data from the 4th and 5th Korea National Health and Nutritional Examination Survey. The subjects were grouped into 2 birth cohorts based on their historical and social context: born from 1946 to 1962 and from 1963 to 1978. The dependent variables were periodontitis and severe periodontitis, while the independent variable was the height quartile. Demographic factors (age and gender), socioeconomic position (own education, region and income), health behaviors (frequency of daily tooth brushing and smoking) and medical status (diabetes) were included. Logistic regression analyses estimated the association of adult height with periodontitis after sequential adjustments., Results: The sample size of the final analysis was 18 010. The shortest quartile was associated with severe periodontitis (OR = 1.55, 95% CI 1.11-2.16) in the 1963-1978 birth cohort. The association remained after full adjustment in the 1963-1978 birth cohort (OR = 1.41, 95% CI 1.01-1.97)., Conclusion: Our study shows that there is an inverse association between height and severe periodontitis only in the younger Korean birth cohort. Our results support the impact of height, as an early childhood environmental indicator, on severe periodontitis in adulthood., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To determine the compounds responsible for its anti-influenza activities, we isolated the three flavonoids, 6-hydroxyluteolin 7-O-β-d-glucoside (1), nepitrin (2), homoplantaginin (3) from the MeOH extract of Salvia plebeia R.Br. and identified them by comparing the spectroscopic data with that reported in the literature. The contents of the three flavonoids in the whole extract were 108.74 ± 0.95, 46.26 ± 2.19, and 69.35 ± 1.22 mg/g for 6-hydroxyluteolin 7-O-β-d-glucoside, nepitrin, and homoplantaginin, respectively, which demonstrates that they are the major constituents of this plant. The three flavonoids were evaluated for their inhibitory activities against influenza virus H1N1 A/PR/9/34 neuraminidase and H1N1-induced cytopathic effect (CPE) on Madin-Darby canine kidney (MDCK) cells. Our results demonstrated the following arrangement for their anti-influenza activities: nepitrin (2) > 6-hydroxyluteolin 7-O-β-d-glucoside (1) > homoplantaginin (3). The potent inhibitory activities of these flavonoids against influenza suggested their potential to be developed as novel anti-influenza drugs in the future.

Background: Chronic exposure to occupational noise is reported to cause a wide range of health problems. But, there are no reports on studies investigating the association between noise exposure and periodontitis. The purpose of this study was to examine the relationship between occupational noise exposure and periodontitis in a nationally representative sample of Korean workers., Methods: This cross-sectional study used data from the 4 th Korean National Health and Nutrition Examination Survey. The study sample included 8,927 workers aged 19 to 54 years. Noise exposure assessment was performed by using self-report questionnaires. The dependent variable was periodontitis. Age, sex, perceived stress level, place of residence, income, education, health behaviors (frequency of daily toothbrushing, binge drinking, smoking status, regular dental checkup), diabetes, obesity, and white blood cell count were included as covariates. Logistic regression analyses estimated the association between noise exposure and periodontitis after sequential adjustment., Results: Compared with never-exposed individuals, participants exposed to occupational noise had an increased prevalence of periodontitis. The association remained significant after full adjustment of covariates (odds ratio [OR] 1.34; 95% confidence interval [CI] 1.06 to 1.70). Association of noise exposure with periodontitis was particularly strong for individuals aged < 45 years (OR 1.65; 95% CI 1.22 to 2.23)., Conclusions: Our study shows that there is an association between occupational noise exposure and periodontitis in a representative sample of Korean workers. Policy efforts to improve workplace noise environments might have an effect on improving periodontal health status among Korean workers., (© 2018 American Academy of Periodontology.)

Sjögren-Larsson syndrome (SLS) is caused by an autosomal recessive mutation in ALDH3A2, which encodes the fatty aldehyde dehydrogenase responsible for the metabolism of long-chain aliphatic aldehydes and alcohols. The pathophysiologic accumulation of aldehydes in various organs, including the skin, brain, and eyes, leads to characteristic features of ichthyosis, intellectual disability, spastic di-/quadriplegia, and low visual acuity with photophobia. The severity of the clinical manifestations thereof can vary greatly, although most patients are bound to a wheelchair due to contractures. To date, correlations between genotype and phenotype have proven difficult to document due to low disease incidence and high heterogenetic variability in mutations. This review summarizes the clinical characteristics of SLS that have been found to contribute to the prognosis thereof, as well as recent updates from genetic and brain imaging studies. In addition, the differential diagnoses of SLS are briefly illustrated, covering cerebral palsy and other genetic or neurocutaneous syndromes mimicking the syndrome., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

[This corrects the article on p. 95 in vol. 61, PMID: 29372155.].

Objective: Few data exist regarding adjuvant hysterectomy (AH) in locally advanced cervical cancer (LACC) patients treated with chemoradiotherapy. We investigated the effect of AH on prognosis in LACC patients, through meta-analysis., Methods: EMBASE and MEDLINE databases and the Cochrane Library were searched for published studies comparing LACC patients who received AH after chemoradiotherapy with those who did not, through April 2016. Endpoints were mortality and recurrence rates. For pooled estimates of the effect of AH on mortality/recurrence, random- or fixed-effects meta-analytical models were used., Results: Two randomized trials and six observational studies (AH following chemoradiotherapy, 630 patients; chemoradiotherapy, 585 patients) met our search criteria. Fixed-effects model-based meta-analysis indicated no significant difference in mortality between the groups (odds ratio [OR]=1.01; 95% confidence interval [CI]=0.58-1.78; p=0.968) with low cross-study heterogeneity (p=0.73 and I²=0.0). This pattern was observed in subgroup analysis for study design, radiation type, response after chemoradiotherapy, and hysterectomy type. The pooled OR for AH and recurrence was 0.59 (95% CI=0.44-0.79; p<0.05) with low cross-study heterogeneity (p=0.29 and I²=17.8), favoring the AH group. However, this pattern was not observed in the subgroup analysis for the randomized trials. There was no evidence of publication bias., Conclusion: In this meta-analysis, AH following chemoradiotherapy did not improve survival in patients with LACC, although it seemed to reduce the risk of recurrence. Concerning the significant morbidity of AH after chemoradiotherapy, routine use of AH should be avoided., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Purpose: The purpose of this study was to evaluate the contributions and limitations of the cervical cancer screening test with accuracy in Korea., Methods: This was a retrospective observational study. The study population consisted of all participants who underwent cervical cancer screening test from 2009 to 2014. The data were obtained from National Health Information Database (NHID) which represents medical use records of most Koreans. As the indices for contributions and limitations of the screening test, crude detection rate, incidence rate of interval cancer, sensitivity, specificity, and positive predictive value were used., Results: The crude detection rate of screening test per 100,000 participants increased from 100.7 in 2009 to 102.1 in 2014. The incidence rate of interval cancer per 100,000 negatives decreased from 13.0 in 2009 to 10.2 in 2014. The sensitivities of screening test were 88.7% in 2009 and 91.2% in 2014, and the specificities were 98.5% in 2009 and 97.7% in 2014. The positive predictive value of screening decreased from 6.2% in 2009 to 4.3% in 2014., Conclusion: The Korean national cervical cancer screening program has improved in accuracy and has contributed to detection of early stage of cervical cancer over the years. Along with efforts to promote participation in cancer screening programs, quality control over the screening program should be enhanced., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: This study demonstrates the biological and chemical analysis of the mushroom Armillariella tabescens (Scop.) Sing. (Tricholomataceae)., Methods: Chemical structures of the isolates were determined by 1D and 2D NMR, and ESI-MS, as well as comparison with previously reported data. All isolates were tested for anti-inflammatory effects based on their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells., Key Findings: We found that the MeOH extract of the fruiting bodies of A. tabescens showed antigastritis activity against ethanol-induced gastric damage in rats and notably reduced the gastric damage index compared to control in a concentration-dependent manner. Chemical investigation of the MeOH extract led to the isolation of four steroids (1-4), three alkaloids (5-7), two nucleic acids (8-9) and four fatty acids (10-13). This is the first study to report the identification of all isolates, except for compound 7, from A. tabescens. Compounds 1, 2, 3, 4 and 10 showed inhibition on LPS-stimulated NO production. Treatment with compound 10 inhibited expression of iNOS, COX-2, phospho-IKKα, IKKα, phospho-IκBα, IκBα and NF-kappa B in LPS-stimulated RAW264.7 cells., Conclusions: Compound 10 likely contributes to the health benefits of A. tabescens as an antigastritis agent through its anti-inflammatory effects., (© 2018 Royal Pharmaceutical Society.)

Purpose: The purpose of this article is to investigate the relationship between renal function and disc hemorrhage (DH)., Materials and Methods: This retrospective cross-sectional survey was conducted at Kangbuk Samsung Hospital Health Screening Center between August 2012 and July 2013, and a total of 168,044 participants at least 20 years of age who voluntarily visited the health screening center for systemic and ophthalmologic examinations, including fundus photography, were enrolled. All subjects underwent a physical examination and provided samples for laboratory analysis. Digital fundus photographs of both eyes were taken and reviewed. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine concentration using the Modification of Diet in Renal Disease (MDRD) formula and Cockcroft-Gault (CG) formula. Subjects were stratified by eGFR into quartiles., Results: Among participants, 220 (0.1%) showed DH, and 2376 (1.6%) showed glaucomatous retinal nerve fiber layer defects. The DH group showed higher creatinine and lower eGFR than the non-DH group. A significant trend was observed among higher creatinine, decreased eGFR as obtained by the MDRD and CG formulas, and the prevalence of DH (P for trend ≤0.003, logistic regression analysis). A multiple logistic regression model adjusted for age, sex, hypertension, diabetes, and hyperlipidemia showed that the lowest eGFR quartiles estimated by MDRD and CG were significantly associated with DH compared with the highest eGFR quartile (adjusted odds ratio, 1.96; 95% confidence interval, 1.22-3.14 by CG, 1.86; 95% confidence interval, 1.17-2.96 by MDRD)., Conclusion: Renal function impairment was independently associated with a higher prevalence of DH in a South Korean population.

Phytochemicals have been considered as alternatives for synthetic fungicides because of their biodegradability and low toxicity. In this study, we found that the methanolic extract of Corydalis ternata suppressed the development of plant diseases caused by Puccinia triticina and Colletotrichum coccodes . As the antifungal substance, three isoquinoline alkaloids (dehydrocorydaline, stylopine, and corydaline) were isolated from C. ternata . These active compounds also exhibited in vivo antifungal activity against P. triticina and C. coccodes . Taken together, our results suggest that C. ternata and its active compounds can be used to control plant diseases.

Objective: Chronic 'latent' infection by Toxoplasma gondii is common and most of the hosts have minimal symptoms or they are even asymptomatic. However, there are possible mechanisms by which T. gondii may affect human behavior and it may also cause humans to attempt suicide. This article aimed to investigate the potential pathophysiological relationship between suicide attempts and T. gondii infection in Korea., Methods: One hundred fifty-five psychiatric patients with a history of suicide attempt and 135 healthy control individuals were examined with enzyme-linked immunoassays and fluorescent antibody technique for T. gondii seropositivity and antibody titers. The group of suicide attempters was interviewed regarding the history of suicide attempt during lifetime and evaluated using 17-item Korean version of Hamilton Depression Scale (HAMD), Columbia Suicide Severity Rating Scale (C-SSRS), State-Trait Anxiety Inventory (STAI) and Korean-Barratt Impulsiveness Scale (BIS)., Results: Immunoglobulin G antibodies were found in 21 of the 155 suicide attempters and in 8 of the 135 controls ( p =0.011). The Toxoplasma-seropositive suicide attempters had a higher HAMD score on the depressed mood and feeling of guilt subscales and a higher total score than the seronegative suicide attempters. T. gondii seropositive status was associated with higher C-SSRS in the severity and lethality subscales. T. gondii IgG seropositivity was significantly associated with higher STAI-X1 scores in the suicide attempters group., Conclusion: Suicide attempters showed higher seroprevalence of T. gondii than healthy controls. Among the suicide attempters, the T. gondii seropositive and seronegative groups showed several differences in the aspects of suicide. These results suggested a significant association between T. gondii infection and psychiatric problems in suicidality.

Objective: In 2002, the Korean Society for Affective Disorders developed the guidelines for the treatment of major depressive disorder (MDD), and revised it in 2006 and 2012. The third revision of these guidelines was undertaken to reflect advances in the field., Methods: Using a 44-item questionnaire, an expert consensus was obtained on pharmacological treatment strategies for MDD 1) without or 2) with psychotic features, 3) depression subtypes, 4) maintenance, 5) special populations, 6) the choice of an antidepressant (AD) regarding safety and adverse effects, and 7) non-pharmacological biological therapies. Recommended first, second, and third-line strategies were derived statistically., Results: AD monotherapy is recommended as the first-line strategy for non-psychotic depression in adults, children/adolescents, elderly adults, patient with persistent depressive disorder, and pregnant women or patients with postpartum depression or premenstrual dysphoric disorder. The combination of AD and atypical antipsychotics (AAP) was recommended for psychotic depression in adult, child/adolescent, postpartum depression, and mixed features or anxious distress. Most experts recommended stopping the ongoing initial AD and AAP after a certain period in patients with one or two depressive episodes. As an MDD treatment modality, 92% of experts are considering electroconvulsive therapy and 46.8% are applying it clinically, while 86% of experts are considering repetitive transcranial magnetic stimulation but only 31.6% are applying it clinically., Conclusion: The pharmacological treatment strategy in 2017 is similar to that of Korean Medication Algorithm for Depressive Disorder 2012. The preference of AAPs was more increased.

As an alternative to synthetic pesticides, natural materials such as plant extracts and microbes have been considered to control plant diseases. In this study, methanol extracts of 120 plants were explored for in vivo antifungal activity against Rhizoctonia solani, Botrytis cinerea, Phytophthora infestans, Puccinia triticina, and Blumeria graminis f. sp. hordei. Of the 120 plant extracts, eight plant extracts exhibited a disease control efficacy of more than 90% against at least one of five plant diseases. In particular, a methanol extract of Curcuma zedoaria rhizomes exhibited strong activity against wheat leaf rust caused by P. triticina. When the C. zedoaria methanol extracts were partitioned with various solvents, the layers of n-hexane, methylene chloride, and ethyl acetate showed disease control values of 100, 80, and 43%, respectively, against wheat leaf rust. From the C. zedoaria rhizome extracts, an antifungal substance was isolated and identified as a sesquiterpene ketolactone based on the mass and nuclear magnetic resonance spectral data. The active compound controlled the development of rice sheath blight, wheat leaf rust, and tomato late blight. Considering the in vivo antifungal activities of the sesquiterpene ketolactone and the C. zedoaria extracts, these results suggest that C. zedoaria can be used as a potent fungicide in organic agriculture.

The objective of the present study was to investigate the association between recurrent implantation failure (RIF) and vascular endothelial growth factor ( VEGF ) gene polymorphisms that are associated with various female infertility disorders. A total of 116 women diagnosed with RIF and 218 control subjects were genotyped for the VEGF -2578C>A, -1154G>A, -634C>G and 936C>T polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism assay. The VEGF -2578AA genotype was associated with an increased prevalence (≥4) of RIF [adjusted odds ratio (AOR)=2.77; 95% confidence interval (CI)=1.10-7.02; P=0.031], whereas the VEGF -634CG+GG genotype was associated with an increased incidence of total RIF (AOR=2.03; 95% CI=1.02-4.05; P=0.044) and ≥4 RIF (AOR=3.16; 95% CI=1.19-8.37; P=0.021). The results of the haplotype analysis indicated that -2578A/-1154A/-634G/936C (AOR=1.76; 95% CI=1.03-3.00; P=0.040 for total RIF and AOR=2.11; 95% CI=1.12-3.97; P=0.021 for ≥4 RIF) was associated with the occurrence of RIF. In addition, it was revealed that there was a significant difference in serum prolactin level associated with the VEGF -634C>G polymorphism (P=0.013). Therefore the findings of the present study indicate that the VEGF -2578AA genotype, -634G allele and -2578A/-1154A/-634G/936C haplotype may be genetic markers for susceptibility to RIF. However, further studies on VEGF promoter polymorphisms that include an independent randomized-controlled population are required to confirm these results.

Objective: This study aims to analyze the published literatures on the effect of less radical fertility-preserving procedures, such as conization or simple trachelectomy, on oncological outcomes in IA1 cervical cancer patients with lymphovascular space invasion (LVSI) through a systematic-review., Methods: The EMBASE and MEDLINE databases and Cochrane Library were searched for published studies reporting the oncological outcomes of conization/simple trachelectomy in these patients, through April 2017. The endpoints were recurrence and mortality rates. Data were presented as per the Meta-analysis Of Observational Studies in Epidemiology checklist. Practice guidelines were generated via the Grading of Recommendation, Assessment, Development and Evaluation system., Results: From 6,755 records, 94 full-texts articles were reviewed for eligibility, and five studies were included in this systematic review. All included studies were nonrandomized studies: two case-control studies comparing conization (n = 14) with hysterectomy (n = 24), and the other three were interrupted time series including conization (n = 20) and simple vaginal trachelectomy (n = 59). During the median follow-up duration of 43 months, no recurrence was reported in both conization and simple trachelectomy groups in IA1 patients with LVSI. From three studies reporting the fertility outcomes, the rates of pregnancy, live birth, preterm delivery, and second-trimester miscarriage were 73% (35/48), 64% (32/50), 10% (5/48), and 6% (3/48), respectively., Conclusion: Results suggest that simple trachelectomy or conization could be performed for IA1 cervical cancer patients with LVSI who want to preserve fertility, although these results are only based on a small number of nonrandomized studies (recommendation grade 2 = weak; evidence level D = very low). Further randomized trials with long-term study period are needed to address this issue.

A Rh(III)-catalyzed C-H activation reaction has been developed for the preparation of pyridinium salts from secondary allylamines and internal alkynes. The pyridinium salts formed by this N-annulation reaction have interesting fluorescence properties. This protocol has been applied to the surface modification of mesoporous silica materials to generate functionalized silica that can be used for the detection of nitrobenzene.

Genomic imprinting is the process of epigenetic modification whereby genes are expressed in a parent-of-origin dependent manner; it plays an important role in normal growth and development. Parthenogenetic embryos contain only the maternal genome. Parthenogenetic embryonic stem cells could be useful for studying imprinted genes. In humans, mature cystic ovarian teratomas originate from parthenogenetic activation of oocytes; they are composed of highly differentiated mature tissues containing all three germ layers. To establish human parthenogenetic induced pluripotent stem cell lines (PgHiPSCs), we generated parthenogenetic fibroblasts from ovarian teratoma tissues. We compared global DNA methylation status of PgHiPSCs with that of biparental human induced pluripotent stem cells by using Illumina Infinium HumanMethylation450 BeadChip array. This analysis identified novel single imprinted CpG sites. We further tested DNA methylation patterns of two of these sites using bisulfite sequencing and described novel candidate imprinted CpG sites. These results confirm that PgHiPSCs are a powerful tool for identifying imprinted genes and investigating their roles in human development and diseases.

Background: Non-invasive prenatal screening (NIPS) of trisomy 21 (T21) using digital PCR (dPCR) with several advantages will be very effective. Here, we developed a dPCR system for T21 screening which allows high sensitivity and real-time diagnosis and thus overcome sequence based analysis., Methods: Cut-off value was established using DNA extracted from all 157 T21 negative samples including 47 pregnant woman samples and 3 T21 positive pregnant woman samples extracted from 4 different sample types. To increase the portion of the cell-free fetal DNA (cffDNA) in maternal cell-free DNA (cfDNA), a size selection method was devised. We evaluated the clinical reliability of NIPS using dPCR through analysis of 877 pregnant woman samples., Results: We could demonstrate the possibility of NIPS using dPCR performed by applying cut-off value and size selection method. The overall accuracy was derived at 99.66% using 877 pregnant woman plasma samples., Conclusion: Our results showed that dPCR can meet the requirements for NIPS for T21. It is relatively inexpensive, easy to use in a screening method and compatible with ethical concerns regarding access to nucleotide sequence information. This study may be a basic data for the development of population-wide screening for T21 in pregnant women., (Copyright © 2017. Published by Elsevier B.V.)

The purpose of this study was to assess the relationship of dental caries with anthropometric outcomes in 4- to 6-year-old children participating in the Korean National Health and Nutrition Examination Survey (KNHANES). The sample size was 1,910 children from the 4th and 5th KNHANES. The caries status was assessed with the decayed and filled teeth index in primary dentition (dft score). We employed height for age, body weight for age, and body mass index for age as outcome variables. Age, gender, region, and income were confounders. Nutritional deficiency as a mediator in the association between dental caries and delayed growth was also examined. A series of logistic regression analyses estimated the magnitude of association between dental caries and unfavorable growth after adjustment of the confounders and the mediator. Those with a high dft score were more likely to be deficient in nutrition (OR 1.77, 95% CI 1.14-2.74). After adjusting for sociodemographic factors and nutritional deficiency, we also found that a high dft score was associated with low weight (OR 1.70, 95% CI 1.15-2.51). The influence of dental caries on delayed growth was found in Korean representative children., (© 2017 S. Karger AG, Basel.)

Objective: Indications for preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles and clinical outcomes were evaluated at CHA Gangnam Medical Center., Methods: This is retrospective cohort study. All patients (n=336) who went through in vitro fertilization (IVF)-PGD/PGS cycles (n=486) between January 2014 and December 2015 were included in Fertility Center of CHA Gangnam Medical Center. Patients underwent IVF-PGD/PGS with 24-chromosome screening. Patients with euploid embryos had transfer of one or 2 embryos in a fresh cycle with any subsequent frozen embryo transfer (ET) cycle. Compared implantation, clinical pregnancy, ongoing pregnancy, and early abortion rates were the main outcome measures., Results: The most common indication for PGD/PGS was recurrent spontaneous abortion (n=160). The chromosome rearrangement cases (n=116) included 24 Robertsonian translocations, 60 reciprocal translocations, 3 inversions, 2 deletions, 4 additions, and 23 mosaicisms. PGS cases rather than the PGD cases showed higher implantation rates (26.4% vs. 20.3%), ongoing pregnancy rates (19.5% vs. 16.4%), and clinical pregnancy rates (28.6% vs. 23.3%). Implantation rates (30.3% vs. 23.7%), clinical pregnancy rates (39.2% vs. 25.2%), and ongoing pregnancy rates (25.7% vs. 17.5%) were significant higher in the blastocyst evaluation group than cleavage stage evaluation group., Conclusion: This was the largest study of PGD/PGS for 2 years at a single center in Korea. The pregnancy outcomes of PGD cases are slightly lower than PGS cases. It was confirmed again that success rate of PGD/PGS is higher if biopsy was done at blastocyst than cleavage stage., Competing Interests: Conflict of interest: No potential conflict of interest relevant to this article was reported.

A three-beam femtosecond stimulated Raman scattering (SRS) scheme is formulated and demonstrated to simultaneously induce two different SRS processes associated with Raman-active modes in the same molecule. Two SR gains involving a common pump pulse are coupled and compete: As one of the Stokes beam intensities increases, the other SRS is selectively suppressed. We provide theoretical description and experimental evidence that the selective suppression behavior is due to the limited number of pump photons used for both of the two SRS processes when an intense depletion beam induces one SRS process. The maximum suppression efficiency was ∼60% with our experimental setup, where the SR gain of the ring breathing mode of benzene is the target SRS signal, which is allowed to compete with another SRS process, induced by an intense depletion beam, of the CH stretching mode. We anticipate a potential of this new switching-off concept in super-resolution label-free microscopy.

Background: Bacterial biofilms exhibit reduced sensitivity to conventional antibiotics and host defence systems and contribute to the persistence of chronic bacterial infections., Hypothesis: The antibiofilm approach using plant alkaloids provides an alternative to antibiotic strategies., Study Design: In this study, the antibiofilm activities of various plant alkaloids were investigated against enterohemorrhagic Escherichia coli O157:H7 and Pseudomonas aeruginosa. In the subsequent investigation, the effects of five norharmane derivatives were investigated., Result: Harmaline significantly inhibited biofilm formation by E. coli O157:H7, P. aeruginosa PAO1, P. aeruginosa PA14, and Klebsiella oxytoca, and norharmane (β-carboline) was found to have antibiofilm activity. It was also found that functional groups at the C-1 and C-7 positions of norharmane could play important roles in its antibiofilm activity. Confocal and electron microscopic observations confirmed biofilm inhibition by harmaline and norharmane, and both reduced fimbriae production and swarming and swimming motilities. Furthermore, harmaline and norharmane attenuated the virulence of E. coli O157:H7 in a Caenorhabditis elegans nematode model., Conclusion: These findings strongly suggest that harmaline and norharmane could have potential use in antibiofilm strategy against persistent bacterial infections., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Purpose: To investigate risk factors associated with glaucomatous progression in pseudoexfoliation glaucoma (PXG) patients., Patients and Methods: A retrospective observational study with a total of 48 PXG patients and age, sex, and visual field (VF) test mean deviation-matched 48 primary open-angle glaucoma (POAG) patients recruited from 3 university-based hospitals. Glaucomatous progression was defined by 2 criteria, either optic disc/retinal nerve fiber layer photographic assessment or serial VF data. Univariate and multivariate Cox proportional hazard models were used to detect associations between risk factors and progression in each subgroup and shared frailty model were used in total participants., Results: In total participants, PXG diagnosis [hazard ratio (HR), 7.245; P=0.050], a higher baseline intraocular pressure (IOP) (HR, 1.221; P=0.025) and a greater number of glaucoma medications (HR, 3.537; P=0.016) were significant factors for glaucoma progression. In the PXG group, a higher baseline IOP (HR, 1.131; P<0.001), a lower IOP reduction (HR, 0.966; P=0.027), a greater number of glaucoma medications (HR, 2.413; P=0.004), and worse baseline VF mean deviation (HR, 0.875; P=0.004) were significant factors, whereas the number of glaucoma medications (HR, 3.493; P=0.019) and disc hemorrhage (HR, 3.953; P=0.043) showed association in the POAG group., Conclusions: Factors associated with progression differed between PXG and POAG groups. Higher baseline IOP and requirement for a greater number of glaucoma medications were related with PXG progression.