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Ye Rim Kim,1,2,&ast; Sung Won Chung,1,2,&ast; Min-Ju Kim,3 Won-Mook Choi,1,2 Jonggi Choi,1,2 Danbi Lee,1,2 Han Chu Lee,1,2 Ju Hyun Shim1,2,4 1Division of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Liver Cancer Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea; 3Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Ju Hyun Shim, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-02-3010-3190, Fax +82-02-485-5782, Email s5854@amc.seoul.krIntroduction: We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients.Methods: Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models.Results: Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps< 0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39– 1.59]) and non-curative (1.22 [1.17– 1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74– 0.92]) and best supportive care (0.85 [0.79– 0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48– 2.00]) and ablation (1.44 [1.08– 1.92]).Conclusion: Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.Keywords: BCLC, UICC, liver cancer, retrospective cohort, external validation

Hyun Ji Cha,1,&ast; Chang-Hyun Han,2,3,&ast; Ju Hyun Jeon,1 Jeong Kyo Jeong,1 In Chul Jung,4 Changsop Yang,2 Byoung-Kab Kang,2 Min Ji Kim,5 Young Eun Choi,5 Young Il Kim1 1Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 2Korean Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 3Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 4Department of Oriental Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Young Il Kim, Tel +82-42-470-9137, Email omdkim01@dju.krPurpose: Pharmacopuncture therapy has been used in the conservative treatment of rotator cuff disease adjuvant to acupuncture treatment. Despite the increasing utilization of pharmacopuncture therapy, there is still a lack of high-quality research to support its effectiveness. This pilot study aimed to assess the feasibility of pharmacopuncture therapy adjuvant to acupuncture treatment for rotator cuff disease.Patients and Methods: This was a parallel-grouped, pragmatic randomized controlled, pilot study. Forty patients were randomly allocated to either the experimental or the control group. All patients received acupuncture treatment for four weeks, and pharmacopuncture was additionally administered to the experimental group. After eight treatments were delivered over four weeks, follow-up assessments were performed. The primary outcome was the mean change in the visual analog scale (VAS) score for shoulder pain from baseline to visit 8. Secondary outcomes included shoulder pain and disability index (SPADI) at visits 4, 8, and 9, shoulder range of motion (ROM) at visits 4, 8, and 9, EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at visits 8 and 9, patient global impression of change (PGIC) at visits 8 and 9, and mean rescue medication consumption at visits 8 and 9.Results: Both groups showed that each treatment effectively improved rotator cuff disease in most assessments. Particularly, the group that received acupuncture plus pharmacopuncture required fewer rescue medications than the group that received acupuncture alone. However, there was little statistically significant difference between the two groups. There were no serious adverse events experienced by patients in this study.Conclusion: Although there was little statistical difference between the two groups, the combination of acupuncture and pharmacopuncture for rotator cuff disease was associated with a reduction in the rescue medicine dosage compared with acupuncture alone. Also, it confirmed the safety of pharmacopuncture therapy. This pilot study would help design future research on the effectiveness of pharmacopuncture in rotator cuff disease.Keywords: rotator cuff disease, pharmacopuncture, acupuncture, pragmatic trial, randomized controlled trial

Su-Hwa Lee,1,&ast; Ki-Back Chu,2,&ast; Min-Ju Kim,3 Fu-Shi Quan1,2 1Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 3Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Fu-Shi Quan, Department of Medical Zoology, School of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea, Tel/Fax +82-2-961-2302, Email fsquan@khu.ac.krPurpose: Heterologous virus-like particle (VLP) assembly involving influenza or the Newcastle disease virus matrix protein (M) has been extensively used to explore the efficacies of VLP vaccines against the respiratory syncytial virus (RSV). Here, we attempted to generate homologous RSV VLPs by expressing the pre-fusion (pre-F) or the glycoprotein (G) on the RSV M protein and evaluated their protective efficacy in mice.Methods: We generated VLPs using the baculovirus expression system in Spodoptera frugiperda (Sf9) insect cells. Recombinant baculoviruses expressing the RSV pre-F, G, and M antigens were inoculated into Sf9 cells, and particles were self-assembled. Mice were immunized with either pre-F or G-expressing VLPs, and immune parameters were assessed to determine protection.Results: Our findings show that successful VLP assembly can be achieved by utilizing recombinant baculoviruses expressing the RSV pre-F or G proteins with the native matrix protein. Mice immunized with either pre-F or the G antigen-expressing VLPs elicited robust serum-mediated virus neutralization. VLP immunization evoked Th1-biased RSV-specific antibody responses in the sera of mice. Following challenge infection with the RSV A2 strain, immunized mice experienced lesser eosinophil and IL-4 accumulation in the lungs, though a substantial increase in TNF-α secretion was observed from CD4+ T cells. Interestingly, splenic antibody-secreting cell responses were substantially enhanced against RSV F antigen, but not against the RSV G antigen following immunization and challenge infection. Immunizing mice with the VLPs significantly inhibited pulmonary histopathology development, as indicated by the diminished inflammatory immune cell influx and mucin secretion.Conclusion: Combined, these vaccine-induced immune responses contributed to successfully inhibiting the RSV replication in the lungs of mice and demonstrated that RSV VLP assembly using insect cell-derived homologous RSV matrix protein is a feasible approach.Keywords: vaccine, protection, native virus antigen, recombinant baculovirus

Kyoung Sun Park,1 Changnyun Kim,2 Joo Won Kim,3 Sang‐Don Kim,4 Jee Young Lee,5 Yoon Jae Lee,5 Jinho Lee,1 Min Ji Kim,6 Young Eun Choi,6 Changsop Yang,7 Chang-Hyun Han,7,8,&ast; In-Hyuk Ha5,&ast; 1Jaseng Hospital of Korean Medicine, Seoul, Republic of Korea; 2Daejeon Jaseng Hospital of Korean Medicine, Daejeon, Republic of Korea; 3Bucheon Jaseng Hospital of Korean Medicine, Bucheon, Republic of Korea; 4Haeundae Jaseng Hospital of Korean Medicine, Busan, Republic of Korea; 5Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea; 6Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 7Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 8Korean Convergence Medical Science, Korea Institute of Oriental Medicine School, University of Science & Technology, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chang-Hyun Han, Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea, Tel +82 42 868 9498, Email chhan@kiom.re.kr In-Hyuk Ha, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea, Tel +82 2 2222 2740, Email hanihata@gmail.comPurpose: Chronic lower back pain (LBP) is a major global health concern. Pharmacopuncture has been widely used to treat LBP in Korea; however, randomized clinical trials (RCT) or active control have not been conducted to evaluate its effectiveness. Therefore, this RCT aimed to compare the effectiveness of pharmacopuncture and physical therapy (PT) for the treatment of chronic LBP.Patients and Methods: A two-arm, parallel, and multicenter RCT was conducted at four hospitals of Korean medicine. Participants with chronic LBP were randomly assigned at a 1:1 ratio using block randomization to undergo 10 sessions of pharmacopuncture or PT over 5 weeks and followed up for 25 weeks. The numerical rating scale (NRS) and visual analog scale scores of LBP and radiating leg pain and the Oswestry disability index (ODI), 5-level EuroQol-5 dimension (EQ-5D-5L), and the patient global impression of change were recorded at baseline and at 6, 13, and 25 weeks. An intention-to-treat analysis was conducted as the primary analysis using a linear mixed model.Results: One-hundred patients (mean age, 49.27 years; 58 women) were recruited. At 6 weeks after randomization, pharmacopuncture showed statistically superior results compared with PT in LBP (difference in NRS, 1.54; 95% CI, 0.94– 2.13), function (difference in ODI, 4.52%; 95% CI, 0.93– 8.11%), and quality of life (difference in EQ-5D-5L) scores (− 0.05; 95% CI, − 0.08 to − 0.01). This effect persisted for 25 weeks. In the survival analysis for participants with at least a 50% reduction in the NRS scores of LBP during the 182-day follow-up, the pharmacopuncture group showed significantly faster recovery than the PT group (P< 0.001, Log rank test).Conclusion: Pharmacopuncture significantly reduced pain and improved functional outcomes and quality of life in patients with low back pain compared with physical therapy. Based on the findings of this study, pharmacopuncture could be recommended as a treatment for patients with chronic low back pain.Keywords: low back pain, pharmacopuncture, physiotherapy, Oswestry disability index, Roland–Morris disability questionnaire, pragmatic randomized controlled trial

Youna Paik,1 Min Joo Kim,1 Hyeryeong Kim,1 Sun-Woo Kang,2 Youn-Kyung Choi,3,&ast; Yong-Il Kim1,4,&ast; 1Department of Orthodontics, Dental Research Institute, Pusan National University Dental Hospital, Yangsan, South Korea; 2Department of Prosthodontics, Dong-A University Hospital, Busan, South Korea; 3Department of Orthodontics, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea; 4Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, South Korea&ast;These authors contributed equally to this workCorrespondence: Youn-Kyung Choi; Yong-Il Kim, Tel +82-51-240-7430 ; +82-55-360-5163, Fax +82-51-240-7706 ; +82-55-360-5154, Email dolldreaming@naver.com; kimyongil@pusan.ac.krPurpose: To evaluate the remineralization effect of calcium phosphate ion clusters (CPICs) on demineralized enamel surfaces and their effects on bracket shear bond strength.Patients and Methods: Extracted premolars were prepared in resin blocks. The samples in the form of resin blocks were divided into five experimental groups: control group, demineralized group, and groups of CPIC solution treatment for 30, 60, and 90s. The specimens were examined using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDX), microhardness testing, micro-computed tomography (micro-CT) assessment, shear bond strength (SBS) test, and adhesive remnant index (ARI) score.Results: The SEM images revealed epitaxial growth of enamel and a decrease in the thickness of the demineralized enamel layer when treated with CPIC solution. The EDX analysis revealed an increase in the Ca/P ratio in the CPIC-treated groups. The microhardness value significantly increased when treated with CPICs; however, it showed a lower value than that of the sound enamel groups. As a result of the micro-CT test, radiolucency decreased gradually as the CPIC treatment time increased. The SBS test and ARI score results showed an improvement in bonding stability after treatment with CPICs.Conclusion: We demonstrated an enamel biomodification approach using CPIC solution treatment, which is a promising strategy for enamel remineralization. Specifically, remineralization of demineralized enamel improves the orthodontic bracket SBS.Keywords: calcium phosphate ion cluster, enamel remineralization, shear bond strength

Chanda Simfukwe,1 Young Chul Youn,1 Min-Jae Kim,2 Joonki Paik,2 Su-Hyun Han1 1Department of Neurology, Chung-Ang University College of Medicine, Seoul, South Korea; 2Department of Image, Chung-Ang University, Seoul, South KoreaCorrespondence: Young Chul Youn; Su-Hyun Han, Department of Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea, Email neudoc@cau.ac.kr; freesu84@cau.ac.krPurpose: Electroencephalogram (EEG) signals give detailed information on the electrical brain activities occurring in the cerebral cortex. They are used to study brain-related disorders such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Brain signals obtained using an EEG machine can be a neurophysiological biomarker for early diagnosis of dementia through quantitative EEG (qEEG) analysis. This paper proposes a machine learning methodology to detect MCI and AD from qEEG time-frequency (TF) images of the subjects in an eyes-closed resting state (ECR).Participants and Methods: The dataset consisted of 16,910 TF images from 890 subjects: 269 healthy controls (HC), 356 MCI, and 265 AD. First, EEG signals were transformed into TF images using a Fast Fourier Transform (FFT) containing different event-rated changes of frequency sub-bands preprocessed from the EEGlab toolbox in the MATLAB R2021a environment software. The preprocessed TF images were applied in a convolutional neural network (CNN) with adjusted parameters. For classification, the computed image features were concatenated with age data and went through the feed-forward neural network (FNN).Results: The trained models’, HC vs MCI, HC vs AD, and HC vs CASE (MCI + AD), performance metrics were evaluated based on the test dataset of the subjects. The accuracy, sensitivity, and specificity were evaluated: HC vs MCI was 83%, 93%, and 73%, HC vs AD was 81%, 80%, and 83%, and HC vs CASE (MCI + AD) was 88%, 80%, and 90%, respectively.Conclusion: The proposed models trained with TF images and age can be used to assist clinicians as a biomarker in detecting cognitively impaired subjects at an early stage in clinical sectors.Keywords: neurodegenerative diseases, electroencephalography, supervised machine learning, regression analysis

Kyoung Sun Park,1 Suna Kim,2 Ji Yeon Seo,3 HyunWoo Cho,4 Jee Young Lee,5 Yoon Jae Lee,5 Jinho Lee,1 Min Ji Kim,6 Young Eun Choi,6 Chang Sop Yang,7 Chang-Hyun Han,7,8,&ast; In-Hyuk Ha5,&ast; 1Jaseng Hospital of Korean Medicine, Seoul, Republic of Korea; 2Daejeon Jaseng Hospital of Korean Medicine, Daejeon, Republic of Korea; 3Bucheon Jaseng Hospital of Korean Medicine, Bucheon, Republic of Korea; 4Haeundae Jaseng Hospital of Korean Medicine, Busan, Republic of Korea; 5Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea; 6Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 7KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 8 Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: In-Hyuk Ha, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 2F Vision Tower, 540 Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea, Tel +82 2 2222 2740, Email hanihata@gmail.comPurpose: Chronic low back pain (LBP) is a common musculoskeletal disorder that affects everyday life; moreover, it occasionally causes disability and increases medical expenditure. This pragmatic randomized clinical trial aims to investigate the effects of pharmacopuncture on chronic LBP by comparing the effectiveness of pharmacopuncture and physiotherapy strategies.Patients and Methods: In this two-armed, parallel, multi-center randomized controlled study, the participants will randomly undergo 10 sessions of pharmacopuncture therapy or physiotherapy over five weeks based on the randomization outcomes. The primary outcome will be the numeric rating scale (NRS) score of LBP. The secondary outcomes will include the NRS score of radiating leg pain, visual analog scale (VAS) score of LBP and radiating leg pain, Oswestry disability index, the Korean version of the Roland–Morris disability questionnaire, patient global impression of change (PGIC), short Form-12 health survey version 2, and 5-level EuroQol-5 dimension (EQ-5D-5L).Conclusion: This protocol aims to examine the comparative effectiveness of pharmacopuncture, which is a widely used therapy in Korean medicine, with respect to the standard therapy through a pragmatic randomized controlled trial to present useful data to facilitate clinical or policy decision making.Trial Registration: Clinicaltrials.gov (NCT04833309); Clinical Research Information Service (KCT0006088).Keywords: low back pain, pharmacopuncture, physical therapy, pragmatic randomized controlled trial, protocol, musculoskeletal disorder, Korean medicine

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Ran Kim,1 Seung-Ah Choe,2 Eun A Park,1 Myung Joo Kim,1 Young-Sang Kim,1 You Shin Kim1 1Department of Obstetrics and Gynecology, CHA Fertility Center Seoul Station, CHA University School of Medicine, Seoul, 04637, Korea; 2Department of Preventive Medicine, Korea University College of Medicine, Seoul, 02841, KoreaCorrespondence: Seung-Ah ChoeDepartment of Preventive Medicine, Korea University College of Medicine, Department of Epidemiology & Health Informatics, Graduate School of Public Health, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, KoreaTel +82-2-2286-1344Email seungah@korea.ac.krPurpose: To assess the impact of additional embryo transfer (ET) on pregnancy in young women, we used a natural-experiment approach.Patients and Methods: The design was based on the national policy of South Korea limiting the number of embryos transferred in vitro fertilization (IVF):≦2 embryos on day 2– 4 or one on day 5– 6 for patients aged < 35, with one extra embryo allowed for patients aged ≥ 35. Using the data from 1909 ET cycles of 1287 women aged ≥ 34 and ≤ 35, we calculated adjusted risk ratios (RRs) for pregnancy.Results: Half of cycles were undertaken by women aged 35, and additional ET was performed in 68.7% of them. Intrauterine pregnancy (45.2% vs 51.3%) and multiple gestation (30.5% vs 6.9%) were more common in women aged 35 than in those aged 34. The RR for intrauterine pregnancy was 1.34 (95% confidence interval: 1.12– 1.59) when comparing double ET to single ET in frozen day 5– 6 cycles.Conclusion: We observed no evidence of a higher probability of pregnancy with additional ET in fresh or frozen day 3– 4 ET, or in fresh day 5– 6 ET of women aged 35. Additional ET may not increase the successful pregnancy rate in the 35-year-old group, unless it is a frozen day 5– 6 ET cycle.Keywords: in vitro fertilization, single embryo transfer, pregnancy rate, multiple pregnancy

Jisun Lee,1 Jinyoung Park,2 Hyun Jung Lee,1 Mi Ju Kim,1 Yoon Hee Lee,3 Gun Oh Chong,3 Dae Gy Hong,3 Taek Hoo Lee1 1Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea; 3Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of KoreaCorrespondence: Taek Hoo LeeDepartment of Obstetrics & Gynecology, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of KoreaTel +82-53-200-5735Fax +82-53-423-7905Email thlee@knu.ac.krObjective: The objective of this study is to evaluate the preoperative hematological parameters to predict ovarian torsion in patients with ovarian mature cystic teratoma. We also analyzed the diagnostic value of these makers to predict ovarian necrosis in cases of torsion as well as the effect of torsion on ovarian reserve.Patients and Methods: This is a retrospective study of 132 patients who received either laparoscopic or laparotomy surgery for OMCT at a single university hospital. Clinical characteristics and preoperative hematological parameters were compared between patients with or without torsion. Patients with torsion were further classified as infarction and non-infarction group. Preoperative parameters were compared between the two groups as well.Results: White blood cell (WBC) count, neutrophil percent, neutrophil count, and neutrophil to lymphocyte ratio (NLR) were higher in the torsion group (n=37) than the non-torsion group (n=95) (p< 0.05 for all). Although statistically insignificant, the preoperative anti-Mullerian hormone (AMH) was lower in the torsion group than the non-torsion group (4.07 ± 3.38 vs 6.1 ± 3.6, p=0.122). In cases of torsion, the infarction group showed higher WBC count and lymphocyte count but lower hemoglobin level and platelet to lymphocyte ratio (PLR) than the non-infarction group (p< 0.05 for all).Conclusion: The WBC count, neutrophil percent, neutrophil count, and NLR were higher in the cases of OMCT with torsion, and these parameters may be useful to diagnose OMCT with torsion. Also, adnexal torsion may deteriorate ovarian reserved as indicated by decreased AMH in torsion group.Keywords: leukocyte counts, necrosis, ovarian neoplasm, ovarian teratoma, ovarian reserve, torsion

Changhee Ha,1 Eun Sil Kim,2 Yiyoung Kwon,2 Yon Ho Choe,2 Mi Jin Kim,2 Soo-Youn Lee1,3 1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaCorrespondence: Mi Jin KimDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, KoreaTel +82 2 3410 0951Fax +82 2 3410 0043Email mijin1217.kim@samsung.comSoo-Youn LeeDepartment of Laboratory Medicine and Genetics, Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, KoreaTel +82 2 3410 1834Fax +82 2 3410 2719Email suddenbz@skku.eduAbstract: Pediatric Crohn’s disease (CD) carries a higher genetic susceptibility and an increased risk of a more aggressive disease course than adult CD. Treatment of CD is based on immunomodulatory drugs, such as thiopurines. The enzyme mainly involved in drug metabolism is thiopurine S-methyltransferase (TPMT). An increased concentration of drug metabolites can cause adverse drug effects, such as myelosuppression and hepatotoxicity; therefore, assessing the activity of TPMT is essential both before and during treatment. TPMT genotyping result is not affected by previous thiopurine dose and currently is the primary component of TPMT activity and disease monitoring. Until now, more than 40 allelic variants of the TPMT gene have been reported, with most of them having an uncertain or no enzyme function. In this article, we report the first case of a novel TPMT allele, TPMT*45, that was identified in a Korean girl with CD whose findings suggested decreased TPMT activity. This newly observed variant is caused by a single nucleotide polymorphism resulting in nonsense mutation (c.676C>T, p.R226*) and the partial loss of amino acids in the TPMT protein. Initially, the patient began azathioprine at a standard dosage (1.5 mg/kg/day), and her laboratory results, including red blood cell (RBC) TPMT activity (6-methylmercaptopurine 2.68 nmol/mL/h and 6-methylmercaptopurine riboside 4.82 nmol/mL/h) along with thiopurine metabolite levels (6-thioguanine nucleotides 479.3 pmol/8× 108 RBC), suggested an enzyme deficiency. The thiopurine dose was reduced to half (0.7 mg/kg/day), and the follow-up metabolite results as well as the associated inflammatory markers were continuously within reference ranges. Along with an improvement in the patient’s subjective reports and clinical symptoms, the patient demonstrated a good treatment response to the adjusted dose. The results of our report illustrate the importance of TPMT genotyping and pharmacogenetic-based thiopurine dose adjustment. Further research should focus on the functional characterization and impact on this novel allele’s treatment effect.Keywords: TPMT*45, Crohn’s disease, thioupurine, single nucleotide polymorphism, TPMT activity, drug metabolism

The Fermilab Mu2e experiment has been developed to search for evidence of charged lepton flavor violation through the direct conversion of muons into electrons. The transport solenoid is an s-shaped magnet that guides the muons from the source to the stopping target. It consists of 52 superconducting coils arranged in 27 coil modules. A full-size prototype coil module, with all the features of a typical module of the full assembly, was successfully manufactured by a collaboration between INFN-Genoa and Fermilab. The prototype contains two coils that can be powered independently. To validate the design, the magnet went through an extensive test campaign. Warm tests included magnetic measurements with a vibrating stretched wire and electrical and dimensional checks. The cold performance was evaluated by a series of power tests and temperature dependence and minimum quench energy studies.

Min-Ji Kim,* Jo-Young Son,* Jin-Sook Ju, Dong-Kuk Ahn Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea*These authors contributed equally to this workCorrespondence: Dong-Kuk AhnDepartment of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, KoreaTel +82-53-660-6840Fax +82-53-421-4077Email dkahn@knu.ac.krBackground: Although the Eph receptor plays an important role in the development of neuropathic pain following nerve injury, there has been no evidence of the participation of the ephrin A4 receptor (EphA4) in the development of trigeminal neuropathic pain. The present study investigated the role of EphA4 in central nociceptive processing in rats with inferior alveolar nerve injury.Materials and Methods: Male Sprague-Dawley rats were used in all our experiments. A rat model for trigeminal neuropathic pain was produced using malpositioned dental implants. The left mandibular second molar was extracted under anesthesia, followed by the placement of a miniature dental implant to injure the inferior alveolar nerve.Results: Our current findings show that nerve injury induced by malpositioned dental implants evokes significant mechanical allodynia and up-regulation of EphA4 expression in the ipsilateral trigeminal subnucleus caudalis. Although daily treatment with EphA4-Fc, an EphA4 antagonist, did not produce prolonged anti-allodynic effects after the chronic neuropathic pain had been already established, an early treatment protocol with repeated EphA4-Fc administration significantly attenuated mechanical allodynia before initiation of chronic neuropathic pain. Finally, we confirmed the participation of the central EphA4 pathway in the development of trigeminal neuropathic pain by reducing EphA4 expression using EphA4 siRNA. This suppression of EphA4 produced significantly prolonged anti-allodynic effects.Conclusion: These results suggest that early blockade of central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.Keywords: neuropathic pain, ephrin, EphA4, siRNA, allodynia, trigeminal

Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4-3.8 nm and diameters from 2-23 nm.

Common genetic variants 3′ of MC4R within two large linkage disequilibrium (LD) blocks spanning 288 kb have been associated with common and rare forms of obesity. This large association region has not been refined and the relevant DNA segments within the a

© 2014 Birnbaum et al.In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of

Jong-Lyul Ghim,1–3,* Nguyen Thi Thu Phuong,1–2,4,* Min Jung Kim,1,2 Eun-Ji Kim,5 Geun Seog Song,5 Sangzin Ahn,1,2 Jae-Gook Shin,1,2 Eun-Young Kim1–31Department of Pharmacology and Clinical Pharmacology, PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea; 2Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Busan, Republic of Korea; 3Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea; 4Faculty of Pharmacy, Hai Phong University of Medicine and Pharmacy, Haiphong, Vietnam; 5CJ HealthCare Co., Ltd, Seoul, Republic of Korea*These authors contributed equally to this workPurpose: The aims of this study was to investigate the mutual pharmacokinetic interactions between steady-state atorvastatin and metformin and the effect of food on the fixed-dose combined (FDC) tablet of atorvastatin and metformin extended release (XR).Subjects and methods: Study 1, an open-labeled, fixed sequence, multiple-dose pharmacokinetic drug-drug interaction study, was divided into 2 parts. Atorvastatin (40 mg) or metformin (1,000 mg) XR tablets were administered once daily via mono- or co-therapy for 7 days. Plasma levels of atorvastatin and 2-OH-atorvastatin, were quantitatively determined for 36 h in part A (n=50) while metformin plasma concentration was measured up to 24 h in part B (n=16) after the last dosing. Study 2, a randomized, open-labeled, single-dose, two-treatment, two-period, two-sequence crossover study, involved 27 healthy subjects to investigate the impact of food intake on the pharmacokinetics of a combined atorvastatin/metformin XR 20/500 mg (CJ-30056 20/500 mg) tablet.Results: After multiple doses of mono- or co-therapy of atorvastatin (40 mg) and metformin (1,000 mg) XR, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration–time curve during the dosing interval at steady state (AUCτ,ss) were 1.07 (0.94–1.22) and 1.05 (0.99–1.10) for atorvastatin, 1.06 (0.96–1.16) and 1.16 (1.10–1.21) for 2-OH-atorvastatin, and 1.00 (0.86–1.18) and 0.99 (0.87–1.13) for metformin, respectively. Food delayed time to reach maximum concentration (tmax), decreased atorvastatin Cmax by 32% with a GMR (90% CI) of 0.68 (0.59–0.78), and increased metformin AUCt by 56% with a GMR (90% CI) of 1.56 (1.43–1.69).Conclusion: No clinically relevant pharmacokinetic interaction was seen when atorvastatin was co-administered with metformin. Food appeared to change the absorption of atorvastatin and metformin from an FDC formulation. These alterations were in accordance with those described with the single reference drugs when ingested with food.Keywords: pharmacokinetics, drug interaction, atorvastatin, metformin, food effect

Jin Woong Suh,1 Yongguk Ju,2 Chang Kyu Lee,3 Jang Wook Sohn,1,2 Min Ja Kim,1,2 Young Kyung Yoon1,2 1Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea; 2Institute of Emerging Infectious Diseases, Korea University College of Medicine, Seoul, Republic of Korea; 3Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Republic of Korea Purpose: This study investigated the clinical epidemiology, antimicrobial susceptibility, and molecular epidemiology of Corynebacterium striatum isolates.Patients and methods: An observational study was conducted at a university hospital in the Republic of Korea from August to December 2016. All subjects were patients who tested positive for C. striatum clinically. Clinical data were analyzed to evaluate the microbiological and genotypic characteristics of C. striatum strains.Results: Sixty-seven C. striatum isolates recovered from non-duplicated patients were characterized. Patients were classified into three groups according to the infection type: nosocomial infection (71.6%), health care-associated infection (8.7%), and community-acquired infection (18.8%). The most common clinical specimens were urine (35.8%) and skin abscesses (32.8%). Fifty-two (77.6%) isolates showed multidrug resistance, defined as resistance to ≥3 different antibiotic families. All strains were susceptible to vancomycin and linezolid. Resistance to other antibiotics varied: penicillin (n=65; 97.0%), ampicillin (n=63; 94.0%), cefotaxime (n=64; 95.5%), and levofloxacin (n=61; 91.0%). Phylogenetic analysis identified all 16 S rRNA gene sequences of the 67 isolates as those of C. striatum, where 98%–99% were homologous to C. striatum ATCC 6940. In multilocus sequence typing for internal transcribed spacer region, gyrA, and rpoB sequencing, the most predominant sequence types (STs) were ST2, ST3, ST6, and ST5.Conclusion: C. striatum isolates may cause opportunistic infections associated with nosocomial infections through horizontal transmission. The presence of multidrug resistance and intra-hospital dissemination implicate C. striatum isolates as a potential target pathogen for infection control and antimicrobial stewardship programs. Keywords: Corynebacterium striatum, multidrug resistant, multilocus sequence typing, opportunistic infections, nosocomial infections

Background: Gene expression is controlled by proximal promoters and distal regulatory elements such as enhancers. While the activity of some promoters can be invariant across tissues, enhancers tend to be highly tissue-specific. Results: We compiled sets o

Mi-Ji Kim,1–3 Ki Soo Park,1–3 Ae-Rim Seo,1,2 Sang-Il Lee,4 Yong-Chan Ha,5 Jun-Il Yoo2,3,6 1Department of Preventive Medicine, Gyeongsang National University College of Medicine, Jinju, Republic of Korea; 2Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Republic of Korea; 3Center for Farmer’s Safety and Health, Gyeongsang National University Hospital, Jinju, Republic of Korea; 4Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea; 5Department of Orthopedic Surgery, Chung-Ang University Hospital, Seoul, Republic of Korea; 6Department of Orthopedic Surgery, Gyeongsang National University Hospital, Jinju, Republic of Korea Purpose: The purposes of this study were to investigate the effect of hand-grip strength (HGS) on the Disabilities of the Arm, Shoulder, and Hand (DASH) score in women with upper extremity musculoskeletal disorders (UEMDs) living in rural communities and examine whether upper extremity diseases affected upper extremity functional activity in each group (normal/low HGS) and whether grip strength (GS) was an effect modifier in upper extremity functional activity. Methods: A total of 239 women older than 60 years who had completed a medical workup for epicondylitis, rotator cuff tears, and/or hand osteoarthritis were included in the final study. Functional activity was assessed by DASH, and muscle strength was measured by GS. Low HGS was defined according to the Asian Working Group for Sarcopenia (HGS

With the first test of LQS03, the long quadrupole (LQ) R&D by LARP (the US LHC Accelerator Research Program, a collaboration of BNL, FNAL, LBNL, and SLAC) is approaching conclusion. LQS03 is the third 3.7-m-long quadrupole, with 90 mm aperture, using a full new set of Nb3Sn coils. The LQS03 coils were made using 108/127 RRP strand (with 108 Nb3Sn subelements) produced by Oxford Superconducting Technology, whereas both previous models used 54/61 RRP strand (with 54 larger Nb3Sn subelements). In this paper, LQS03 test results are presented and discussed. The test results are also compared with the performances of the previous models. Observations are made for the future use of Nb3Sn in accelerator magnets. © 2002-2011 IEEE.

With the first test of LQS03, the long quadrupole (LQ) R&D by LARP (the US LHC Accelerator Research Program, a collaboration of BNL, FNAL, LBNL, and SLAC) is approaching conclusion. LQS03 is the third 3.7-m-long quadrupole, with 90 mm aperture, using a full new set of Nb3Sn coils. The LQS03 coils were made using 108/127 RRP strand (with 108 Nb3Sn subelements) produced by Oxford Superconducting Technology, whereas both previous models used 54/61 RRP strand (with 54 larger Nb3Sn subelements). In this paper, LQS03 test results are presented and discussed. The test results are also compared with the performances of the previous models. Observations are made for the future use of Nb3Sn in accelerator magnets. © 2002-2011 IEEE.

After the successful test of the first long Nb 3Sn quadrupole (LQS01) the US LHC Accelerator Research Program (LARP, a collaboration of BNL, FNAL, LBNL and SLAC) is assessing training memory, reproducibility, and other accelerator quality features of long Nb 3Sn quadrupole magnets. LQS01b (a reassembly of LQS01 with more uniform and higher pre-stress) was subjected to a full thermal cycle and reached the previous plateau of 222 T/m at 4.5 K in two quenches. A new set of four coils, made of the same type of conductor used in LQS01 (RRP 54/61 by Oxford Superconducting Technology), was assembled in the LQS01 structure and tested at 4.5 K and lower temperatures. The new magnet (LQS02) reached the target gradient (200 T/m) only at 2.6 K and lower temperatures, at intermediate ramp rates. The preliminary test analysis, here reported, showed a higher instability in the limiting coil than in the other coils of LQS01 and LQS02. © 2011 IEEE.

After the successful test of the first long Nb 3Sn quadrupole (LQS01) the US LHC Accelerator Research Program (LARP, a collaboration of BNL, FNAL, LBNL and SLAC) is assessing training memory, reproducibility, and other accelerator quality features of long Nb 3Sn quadrupole magnets. LQS01b (a reassembly of LQS01 with more uniform and higher pre-stress) was subjected to a full thermal cycle and reached the previous plateau of 222 T/m at 4.5 K in two quenches. A new set of four coils, made of the same type of conductor used in LQS01 (RRP 54/61 by Oxford Superconducting Technology), was assembled in the LQS01 structure and tested at 4.5 K and lower temperatures. The new magnet (LQS02) reached the target gradient (200 T/m) only at 2.6 K and lower temperatures, at intermediate ramp rates. The preliminary test analysis, here reported, showed a higher instability in the limiting coil than in the other coils of LQS01 and LQS02. © 2011 IEEE.

Spencer E Thomas,1,2,* Jeffrey Comer,1,* Min Jung Kim,1 Shanna Marroquin,1 Vaibhav Murthy,1 Meghana Ramani,1 Tabetha Gaile Hopke,2 Jayden McCall,1 Seong-O Choi,1 Robert K DeLong1 1Nanotechnology Innovation Center of Kansas State, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; 2Department of Biomedical Science, Missouri State University, Springfield, MO, USA *These authors contributed equally to this work Introduction: Biomedical applications of nanoparticles (NPs) as enzyme inhibitors have recently come to light. Oxides of metals native to the physiological environment (eg, Fe, Zn, Mg, etc.) are of particular interest—especially the functional consequences of their enzyme interaction. Materials and methods: Here, Fe2O3, zinc oxide (ZnO), magnesium oxide (MgO) and nickel oxide (NiO) NPs are compared to copper (Cu) and boron carbide (B4C) NPs. The functional impact of NP interaction to the model enzyme luciferase is determined by 2-dimensional fluorescence difference spectroscopy (2-D FDS) and 2-dimensional photoluminescence difference spectroscopy (2-D PLDS). By 2-D FDS analysis, the change in maximal intensity and in 2-D FDS area under the curve (AUC) is in the order Cu~B4C>ZnO>NiO>>Fe2O3>MgO. The induced changes in protein conformation are confirmed by tryptic digests and gel electrophoresis. Results: Analysis of possible trypsin cleavage sites suggest that cleavage mostly occurs in the range of residues 112–155 and 372–439, giving a major 45 kDa band. By 2-D PLDS, it is found that B4C NPs completely ablate bioluminescence, while Cu and Fe2O3 NPs yield a unique bimodal negative decay rate, -7.67×103 and -3.50×101 relative light units respectively. Cu NPs, in particular, give a remarkable 271% change in enzyme activity. Molecular dynamics simulations in water predicted that the surfaces of metal oxide NPs become capped with metal hydroxide groups under physiological conditions, while the surface of B4C becomes populated with boronic acid or borinic acid groups. These predictions are supported by the experimentally determined zeta potential. Thin layer chromatography patterns further support this conception of the NP surfaces, where stabilizing interactions were in the order ionic>polar>non-polar for the series tested. Conclusion: Overall the results suggest that B4C and Cu NP functional dynamics on enzyme biochemistry are unique and should be examined further for potential ramifications on other model, physiological or disease-relevant enzymes. Keywords: 2-dimensional fluorescence difference, 2-D FDS, AUC, corrected light intensity emitted, emission wavelength, excitation wavelength, wavelength of max intensity, RLU

Michelle J Kim, Sandra S Stinnett, Preeya K Gupta Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA Purpose: The goal of this study was to evaluate the effect of thermal pulsation treatment on tear film parameters, specifically osmolarity and matrix metalloproteinase-9 (MMP-9), in patients with meibomian gland dysfunction (MGD) and dry eye disease (DED).Methods: A single-center review of 189 eyes that underwent thermal pulsation treatment was performed. Data were collected on pre and posttreatment osmolarity, MMP-9, tear break-up time (TBUT), and ocular surface disease index (OSDI) score. Statistical analyses were performed to detect any significant differences after treatment.Results: Thermal pulsation treatment led to significant improvements in TBUT (mean increase from 4.5 to 8.5 seconds [P307 mOsm/L (ie, diagnostic for DED), there was a significant improvement in the mean tear osmolarity from 317.1 to 306.6 mOsms/L after treatment (P=0.002). Conclusion: Treating MGD is an important component of caring for the DED patient. Thermal pulsation treatment can improve MMP-9 levels on the ocular surface of patients with MGD and DED, as well as improve osmolarity in those with abnormal initial values. The present study suggests that meibomian glands play an important role in tear film dynamics and, as such, effective therapy such as thermal pulsation treatment aimed at improving meibomian gland health, can aid the restoration of normal tear film parameters and decrease patient symptoms of DED and MGD. Keywords: thermal pulsation, dry eye disease, meibomian gland dysfunction, osmolarity, matrix metalloproteinase-9

Hyun-Chang Lim,1,* Ok Hyung Nam,2,* Mi-joo Kim,3 Ahmed El-Fiqi,4,5 Hyung-Mun Yun,3 Yoo-Mi Lee,3 Guang-Zhen Jin,4,5 Hae-Hyoung Lee,5,6 Hae-Won Kim,4–6 Eun-Cheol Kim3 1Department of Periodontology, 2Department of Pediatric Dentistry, 3Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, 4Department of Nanobiomedical Science, BK21 PLUS NBM Global Research Center for Regenerative Medicine, 5Institute of Tissue Regeneration Engineering, 6Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea *These authors contributed equally to this work as first authors Abstract: Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX-releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets α1, α5, and β3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN-matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering. Keywords: drug delivery, therapeutic matrix, dexamethasone, bioactive glass, human dental pulp cells, odontogenic differentiation

Kye Taek Ahn, Kwang-In Park, Mi Joo Kim, Jin Kyung Oh, Ji Hye Han, Hee Jin Kwon, Seon-Ah Jin, Jun-Hyung Kim, Jae-Hyeong Park, Jae-Hwan Lee, Si Wan Choi, In-Whan Seong, Jin-Ok Jeong Department of Internal Medicine, Division of Cardiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Republic of Korea Objectives: Central hemodynamics may better represent the load imposed on the coronary and cerebral arteries and thereby bear a stronger relationship to cardiovascular outcomes. Methods: Patients who had confirmed hypertension as assessed by daytime 24-hour ambulatory blood pressure monitoring (≥135/85 mmHg) were enrolled. Central blood pressure and radial augmentation index (AIx) corrected for a heart rate of 75 bpm (radial AIx 75) were measured for all patients. We evaluated the association of age, height, and sex with central hemodynamics in patients with never-treated hypertension. Results: A total of 203 patients were enrolled, of whom men numbered 101 (49.7%). The median height of all patients was 162 cm, and mean age was 53.2 years. In the Pearson correlation analysis, regardless of sex difference (R=-0.627 for height, R=0.035 for age, P-value =0.005), a stronger relationship was observed between height and radial AIx 75 than between age and radial AIx 75. In the multiple regression analysis, the sex difference and height were strongly associated with elevated radial AIx 75 in all patients (adjusted R2=0.428, β=6.237, 95% confidence interval [CI] for women 1.480–10.995, P-value =0.011 and β=-0.632, 95% CI for height -0.929 to -0.335, P-value =0.009, respectively). Conclusion: In patients with never-treated hypertension, female sex and shorter height are the important risk factors of elevated radial AIx 75. Keywords: hypertension, augmentation index, height, sex

Soowon Park,1,* Se-Eun Park,1,* Min-Ji Kim,2 Hee-Yeon Jung,1,2 Jung-Seok Choi,1,2 Kee-Hwan Park,3 Inhye Kim,1 Jun-Young Lee1,2 1Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 2Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Psychology, The Catholic University of Korea, Bucheon, Republic of Korea *These authors contributed equally to this work Purpose: The purpose of this study was to develop and validate a tool called the Pictorial Cognitive Screening Inventory (PCSI), which consists of pictorial memory and attention tests that are not influenced by literacy level.Patients and methods: PCSI, Mini Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) questionnaires were administered to 80 elderly participants (20 illiterate normal, 20 illiterate with dementia, 20 literate normal, and 20 literate with dementia).Results: PCSI scores were highly correlated with those of the MMSE (r 0.51) and the CDR (r -0.71). In addition, the PCSI scores differed significantly between the normal group and the dementia group (mean difference 1.71, standard error [SE] 0.14, P

Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials.Keywords: TiO2, reactive oxygen species, apoptotic cell death, Fas upregulation, Bax activation, mitochondrial membrane potential loss, caspase activation

Minji Jennifer Kim1, Yong Suk Jo2, Jee Hyun Kim2, Yong-Jin Kim3, Kyung Hwan Kim4, Eun Bong Lee2, Yeong Wook Song2, Eun Young Lee21School of Medicine, University of Manchester, Manchester, UK; 2Division of Rheumatology, 3Division of Cardiology, Department of Internal Medicine, 4Department of Thoracic Surgery, Seoul National University College of Medicine, Seoul, Republic of KoreaAbstract: Budd–Chiari syndrome has been described as a late complication of Behçet’s disease. Although the mortality rate associated with Behçet’s disease is low, it can escalate in the presence of Budd–Chiari syndrome and may be further complicated by intracardial thrombus formation. It is therefore important to detect and initiate management early in the disease course. The imaging modalities of choice should be minimally invasive as certain procedures may aggravate Behçet’s disease by initiating a thrombosis or aggravating an existing one. In Behçet’s disease-induced Budd–Chiari syndrome, cardiac investigation is crucial in the work-up in order to identify any cardiac involvement and determine the etiology of intracardial thrombus. Furthermore, the treatment should ultimately focus on controlling the activity of Behçet’s disease. We report an unusual case of Behçet’s disease presenting with Budd–Chiari syndrome complicated by intracardial thrombus in a young Korean man.Keywords: Behçet’s disease, Budd–Chiari syndrome, intracardial thrombus