OBJECTIVE: To estimate the association between ABCG2 C421A polymorphism and response to imatinib in chronic myeloid leukemia. METHODS: A systematic review was conducted to evaluate the effect of ABCG2 C421A polymorphism on imatinib response. The databases of PubMed, Embase, Web of science, CINAHL with FullText, and Cochrane Library were searched for all published studies from inception to December 2015. The following terms were used with functions of 'AND' and 'OR': 'chronic myeloid leukemia', 'CML', 'drug transporter', 'ABCG2', 'BCRP', 'polymorphisms', 'SNPs', and 'imatinib'. The studies reporting the association between ABCG2 polymorphism and imatinib response were evaluated. RESULTS: A total of 7 studies were included in the present meta-analysis. The pooled analysis showed that ABCG2 c.421CC genotype was significantly associated with poor response to imatinib under the dominant model (CC vs CA+AA; OR: 0.56; 95% CI: 0.41, 0.77; p = 0.0004). The subgroup analysis of Asian studies demonstrated a significantly lower response in c.421CC genotype than in c.421CA or c.421AA genotype (OR: 0.52; 95% CI: 0.37, 0.73; p = 0.0002). In subgroup analyses of 5 studies, the patients with the c.421CC genotype exhibited higher risk for worse response than the patients with c.421CA or c.421AA genotype (heterozygote codominant model: CC vs. AC; OR: 0.49, 95% CI: 0.33, 0.73; p = 0.0006; homozygote codominant model: CC vs AA; OR: 0.43; 95% CI: 0.25, 0.75, p = 0.003). CONCLUSION: The ABCG2 c.421CC genotype was significantly associated with poor response to imatinib compared to the c.421CA and c.421AA genotypes in chronic myeloid leukemia, especially in Asian patients.
Asian Continental Ancestry Group ; Genotype ; Homozygote ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Imatinib Mesylate

OBJECTIVE: A meta-analysis was performed to determine effect of ginseng on blood pressure. METHODS: The databases of PubMed, Embase, Cochrane Library, RISS, DBpia, KISS, and Koreamed were searched for all published studies from inception to January 2016. The following terms were used: "ginseng", "hypertension", and "blood pressure". Using the Review Manager 5, mean differences (MDs) were pooled to measure the effect of ginseng on blood pressure compared to that of placebo. RESULTS: Eleven randomized controlled trials were included. In this meta-analysis, ginseng treatment significantly lowered systolic blood pressure (SBP) in a dose-independent way (MD: -1.99, p = 0.04). In subgroup analysis, 8-12 week consumption of ginseng achieved significantly greater reduction in SBP (MD: -3.14, p = 0.03), while single administration of ginseng failed to show BP-lowering effect. When ingested over 8-12 weeks, ginseng significantly lowered diastolic blood pressure (DBP) (MD: -1.96, p = 0.03). No significant association was found between ginseng dose and the magnitude of BP-lowering effect. However, a significant positive relationship was observed between baseline SBP level and the magnitude of SBP reduction (r = 0.848, p = 0.033). Such a relationship was not seen in DBP. CONCLUSION: Consumption of ginseng for 8-12 weeks achieved significant reductions in SBP and DBP in a dose-independent way. There was a significant positive relationship between baseline SBP level and the magnitude of SBP reduction.
Blood Pressure* ; Panax*

PURPOSE: To report the results of switching treatment to vascular endothelial growth factor (VEGF) Trap-Eye (aflibercept) in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to anti-VEGF (ranibizumab and bevacizumab). METHODS: This is a retrospective study involving 32 eyes from 29 patients; 18 were cases of neovascular AMD and 14 were cases of PCV. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) of spectral-domain optical coherence tomography were evaluated. RESULTS: BCVA and CMT improved from 0.58 to 0.55 (p = 0.005) and from 404 to 321 microm (p < 0.001), respectively, after switching to aflibercept. The 14 eyes that received 6 or more aflibercept injections remained stable at 0.81 to 0.81 and 321 to 327 microm (p = 1.0, 0.29), respectively, after 3 aflibercept injections. The 10 eyes that received 3 or more bevacizumab injections after 3 or more aflibercept injections worsened, from 0.44 to 0.47 and from 332 to 346 microm (p = 0.06, 0.05), respectively. The results showed similar improvement of BCVA and CMT in neovascular AMD and PCV. CONCLUSIONS: Aflibercept seems to be effective for improvement and maintenance of BCVA and CMT for neovascular AMD and PCV refractory to anti-VEGF. Switching from aflibercept back to bevacizumab treatment may not be a proper strategy.
Angiogenesis Inhibitors/administration & dosage ; Bevacizumab/administration & dosage ; Choroid/*blood supply ; Choroid Diseases/complications/diagnosis/*drug therapy ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Intravitreal Injections ; Male ; Ranibizumab/administration & dosage ; Receptors, Vascular Endothelial Growth Factor/*administration & dosage ; Recombinant Fusion Proteins/*administration & dosage ; Retinal Neovascularization/complications/diagnosis/*drug therapy ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/*antagonists & inhibitors ; *Visual Acuity ; Wet Macular Degeneration/diagnosis/*drug therapy/etiology

Objective: Multiple criteria have been proposed to assess the severity of community-acquired pneumonia (CAP) and predict intensive care unit (ICU) admissions. The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker actively researched as a prognostic indicator in various infectious diseases. This study assessed the value of the NLR in predicting ICU admissions among CAP hospitalizations through the emergency department (ED). Methods: A retrospective observational study of hospitalized patients with CAP via ED was performed from March 2017 to December 2018 using electronic medical records from a single center. By analyzing the clinical data at the initial presentation to the emergency room, the predictability of NLR on the admissions to the ICU was compared with other preexisting clinical scores, such as PSI (Pneumonia Severity Index), CURB-65 (Confusion, Uremia, Respiratory rate, Blood pressure, Age ≥ 65 years), and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. Results: Of 599 CAP hospitalizations, 80 (13.4%) required ICU admissions. In multivariate logistic analysis, mean arterial pressure and NLR have significance in predicting ICU admission. The area of under curve (AUC) of preexisting clinical scores to predict ICU admission had a PSI of 0.70, CURB-65 of 0.58, and APACHE II score of 0.66. The AUC of the NLR model was 0.75, the highest among the preexisting scoring systems. Setting the NLR model as a reference value, the PSI and APACHE II scores showed no statistically significant difference in contrast to CURB-65, which showed less powerful predictability. Conclusion NLR is a simple, inexpensive, and rapidly available measurement in the ED, which can be used as a useful tool for predicting ICU admissions among patients with CAP over other preexisting clinical scores.

The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke.
Animals ; Apoptosis ; Cell Differentiation ; *Cell Movement ; Embryonic Stem Cells/cytology/metabolism/*transplantation ; Glial Fibrillary Acidic Protein/genetics/metabolism ; Humans ; Infarction, Middle Cerebral Artery/metabolism/pathology/physiopathology/*surgery ; Male ; Neural Stem Cells/cytology/metabolism/*transplantation ; *Psychomotor Performance ; Rats ; Rats, Sprague-Dawley ; Receptors, CXCR4/genetics/metabolism

BACKGROUND/AIMS: Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Twenty-four-week-old male OLETF rats were assigned to four groups: control (saline), CK 10 mg/kg, CK 25 mg/kg, or metformin 300 mg/kg (positive control); all treatments were administered orally for 12 weeks. RESULTS: Fasting glucose levels of the CK25 group were significantly lower than those of the control group during the 12 weeks. The results of the oral glucose tolerance test showed that both the glucose concentration after glucose loading and the fasting insulin levels of the CK25 group were significantly lower than those of the control. Hepatosteatosis was significantly improved by CK25. CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK). CK25 significantly inhibited the expression of sterol regulatory element-binding protein-1c and fatty acid synthase, while upregulating that of peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1. CONCLUSIONS: CK improved glucose intolerance and hepatosteatosis in HFD-fed OLETF rats through AMPK activation, which has dual mode of action that involves decreasing the synthesis of fatty acids and increasing fatty acid oxidation.
Adenosine ; AMP-Activated Protein Kinases ; Animals ; Carnitine ; Diabetes Mellitus, Type 2 ; Diet, High-Fat ; Fasting ; Fatty Acids ; Ginsenosides ; Glucose Intolerance* ; Glucose Tolerance Test ; Glucose* ; Humans ; Insulin ; Insulin Resistance ; Liver ; Male ; Metformin ; Non-alcoholic Fatty Liver Disease ; Peroxisomes ; Phosphorylation ; Protein Kinases ; Rats ; Rats, Inbred OLETF*

X-linked juvenile retinoschisis (XLRS) is characterized by the progressive loss of visual acuity and vitreous hemorrhage. XLRS is caused by a mutation of retinoschisin 1 (RS1) gene at Xp22.13. In the current report, a 2-year-old Korean patient with XLRS was described. The germline deletion of exon 1 was identified in the RS1 gene. Considering X-linked inheritance pattern, validation of a carrier state of a patient's mother is important for the genetic counseling of other family members and for the future reproductive plan. To confirm the carrier state of his mother, the multiplex ligation-dependent probe amplification analysis was done using peripheral leukocytes and found the heterozygous deletion of exon 1 in his mother.
Carrier State ; Child, Preschool ; Exons ; Genes, X-Linked ; Genetic Counseling ; Humans ; Leukocytes ; Mothers ; Multiplex Polymerase Chain Reaction ; Retinoschisis* ; Visual Acuity ; Vitreous Hemorrhage

Objective: This study aimed to examine the validity of the Korean version of the Autism Diagnostic Interview-Revised (K-ADI-R) and determine its efficacy in identifying individuals with autism spectrum disorder (ASD). Methods: Data were pooled from several past and ongoing studies as well as clinical records acquired at Seoul National University Bundang Hospital from 2008 to 2017. The K-ADI-R were administered and scored by trained research reliable examiners. Measurements to investigate the validity of the K-ADI-R was through sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen’s kappa. Results: A total of 1,271 (age 88.9±62.42 months, male=927) participants were included. The K-ADI-R yielded strong psychometric properties with high sensitivity (86.06–99.27%), specificity (84.75–99.55%), PPV (92.33–99.72%), and NPV (79.43–98.64%). There were significant differences in item scores across the K-ADI-R diagnostic algorithm regardless of age and sex (p<0.001). Agreement between the K-ADI-R and other ASD related measurements ranged between levels of good to excellent. Conclusion Despite language or cultural boundaries, the K-ADI-R demonstrated high levels of sensitivity, specificity, PPV, and NPV within a wide range of participants; hence, suggesting promising usage as a valuable diagnostic instrument for individuals with ASD.

Background and Objectives: The combined intratympanic and oral steroid treatment has been accepted as effective treatment strategy for idiopathic sudden sensorineural hearing loss (ISSNHL). However, the treatment protocol of combined treatment for ISSNHL has not been established. In this study, we investigated whether hearing outcome differed according to different starting timing of intratympanic steroid injection (ITSI) in combined treatment for ISSNHL.Subjects and Method Tertiary academic referral center-based retrospective medical records of idiopathic 144 ISSNHL patients who received combined treatment from January 2015 to April 2018 were reviewed. All patients underwent a 2-week oral systemic steroid treatment and multiple ITSI. The hearing results of 3 months after treatment were compared according to the timing of ITSI. Results: The mean pure tone audiogram gain was 24.3±23.6 dB. When Siegel’s criteria was applied, the overall rate of hearing improvement was 63.9% (92/144). The rate of hearing improvement was significantly higher in women (p=0.043) statistically, and there was a statistically significant lower rate of recovery in the former history of hearing loss (p＜0.01) or otitis media (p＜0.01). Moreover, the shorter the delay between symptom onset and initial ITSI, greater the statistical significance of hearing recovery rate became (p＜0.01). Conclusion The result of this study suggests that early ITSI during combined intratympanic and oral steroid treatment increases the chance of hearing recovery.

Objective: This study aimed to examine the validity of the Korean version of the Autism Diagnostic Interview-Revised (K-ADI-R) and determine its efficacy in identifying individuals with autism spectrum disorder (ASD). Methods: Data were pooled from several past and ongoing studies as well as clinical records acquired at Seoul National University Bundang Hospital from 2008 to 2017. The K-ADI-R were administered and scored by trained research reliable examiners. Measurements to investigate the validity of the K-ADI-R was through sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen’s kappa. Results: A total of 1,271 (age 88.9±62.42 months, male=927) participants were included. The K-ADI-R yielded strong psychometric properties with high sensitivity (86.06–99.27%), specificity (84.75–99.55%), PPV (92.33–99.72%), and NPV (79.43–98.64%). There were significant differences in item scores across the K-ADI-R diagnostic algorithm regardless of age and sex (p<0.001). Agreement between the K-ADI-R and other ASD related measurements ranged between levels of good to excellent. Conclusion Despite language or cultural boundaries, the K-ADI-R demonstrated high levels of sensitivity, specificity, PPV, and NPV within a wide range of participants; hence, suggesting promising usage as a valuable diagnostic instrument for individuals with ASD.