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Jee Eun Lee Department of Business, Korea University, Seoul, 02841, Republic of KoreaCorrespondence: Jee Eun Lee, Department of Business, Korea University, 145, Anam-Ro, Seongbuk-Gu, Seoul, 02841, Korea, Email jelee89@korea.ac.krPurpose: Based on the attribution and appraisal theories of emotion, this study investigates whether a consumer’s frustration and anger after a service failure reduces in different ways after hearing explanations from different sources (other customer vs employee vs none) under different blame attribution circumstances (situational vs service provider), and its subsequent influence on complaining intention.Methods: In Study 1, valid data from 239 participants (46.9% female, Mage=35.6 years) were used to test the interaction effect of the explanation source and blame attribution on frustration and anger. In Study 2, using valid answers from 253 students at Korea University (57.9% female, Mage=20.9 years), Study 1 was replicated and, in addition, tested the moderated mediating impact on complaining intention. The overall theoretical model was tested with ANOVA and Hayes process model 8.Results: When blame attribution was situational, the employee’s explanation did not mitigate either frustration or anger, whereas the other customer’s explanation mitigated frustration but not anger. In contrast, when blame attribution was towards the service provider, the employee’s explanation mitigated both frustration and anger, whereas the other customer’s explanation mitigated only frustration. In addition, the mitigation of frustration and anger by other customers subsequently led to a decrease in complaining intention, which was stronger and only significant when blame attribution was situational. However, only anger acted as a mediator between the employee’s explanation and complaining intention, which did not vary according to blame attribution.Conclusion: The results of the study advance the current knowledge on informational support as a service recovery process by suggesting the crucial role of other consumers in mitigating the target customer’s frustration, especially under situational service failure, which successively leads to a decrease in complaining intention, whereas the employee’s explanation decreases complaining intention only through the mitigation of anger.Keywords: service recovery, other consumer’s explanation, employee’s explanation, frustration, anger

Jeong Eun Lee,1 Jinyoung Oh,1 Jun Nyung Lee,2 Hyun-Su Ri,3 Chang Sub Lee,3 Jinseok Yeo1 1Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea; 2Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea; 3Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Kyungpook National University Hospital, Daegu, KoreaCorrespondence: Jinseok Yeo, Department of Anesthesiology and Pain Medicine Kyungpook National University School of medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea, Tel +82-53-200-2644, Fax +82-53-200-2027, Email painfree@gmail.comBackground: Opioid use after surgery is a potential contributor to the opioid epidemic. An adequate pain control method after surgery while minimizing opioid exposure is needed. This study aimed to compare the effect of non-opioid multimodal analgesia (NOMA) protocol with opioid-based patient-controlled analgesia (PCA) for pain relief after robot-assisted radical prostatectomy (RARP).Methods: This prospective randomized, open, non-inferiority trial included 80 patients scheduled for RARP. The NOMA group received pregabalin, paracetamol, bilateral quadratus lumborum block, and pudendal nerve block. PCA group received PCA. Pain scores, postoperative nausea and vomiting, opioid requirements, and quality of recovery were recorded 48 hours after surgery.Results: We found no significant differences in pain scores. The mean difference in pain score during rest at 24 h was 0.5 (95% CI − 0.5 to 2.0). This result demonstrated the non-inferiority of NOMA protocol to PCA at our non-inferiority margin (− 1). In addition, 23 patients in the NOMA group did not receive any opioid agonist for 48 h after surgery. Recovery of bowel function was also faster in the NOMA group than in the PCA group (25.0 hours vs 33.4 hours, p = 0.01).Limitations: We did not evaluate whether our NOMA protocol could decrease the incidence of new continuous opioid use after surgery.Conclusion: NOMA protocol successfully controlled postoperative pain and was non-inferior to morphine-based PCA regarding patient-reported pain intensity. It also promoted recovery of bowel function and decreased postoperative nausea and vomiting.Keywords: multimodal analgesia, opioid sparing, postoperative pain, robot-assisted radical prostatectomy

Ji-Hyun Kang,1,* Ji-Eun Lee,1,* So-Jeong Jeong,1 Chun-Woong Park,1 Dong-Wook Kim,2 Kwon-Yeon Weon3 1College of Pharmacy, Chungbuk National University, Cheongju, Korea; 2College of Pharmacy, Wonkwang University, Iksan, Korea; 3College of Pharmacy, Daegu Catholic University, Gyeongsan, Korea*These authors contributed equally to this workCorrespondence: Dong-Wook Kim, College of Pharmacy, Wonkwang University, Iksan, 54538, Korea, Tel +82-63-229-7130, Fax +82-63-850-7309, Email pharmengin@gmail.com Kwon-Yeon Weon, College of Pharmacy, Daegu Catholic University, Gyeongsan, 38430, Korea, Tel +82-53-850-3616, Fax +82-53-850-3602, Email weonky@cu.ac.krPurpose: This study aimed to ensure the convenience of administration and reproducibility of efficacy, regardless of the meal, by improving the solubility of rivaroxaban (RIV).Methods: RIV is a non-vitamin K antagonist oral anticoagulants that exhibits a coagulation effect by directly inhibiting coagulation factor Xa. However, RIV has a very low solubility; therefore, it must be administered with a meal at high doses. We used a drug- hydroxypropyl-beta-cyclodextrin (CD)-water-soluble polymer triple complex (R-C-P complex) to solubilize RIV. Using Minitab, we evaluated the effect of each factor on RIV solubility and developed an optimal R-C-P complex formulation. The amount of CD, amount of polymer, and polymer type were set as the independent variables X1, X2, and X3, respectively. RIV solubility (Y1) and dissolution rate for 45 min in pH 4.5 medium (Y2) and pH 1.2 medium (Y3) were set as response variables.Results: The most efficient RIV solubilization effect was obtained from the composition using CD and HPMC 2208, and physicochemical properties and dissolution parameters were analyzed. RIV in the R-C-P complex was present in an amorphous form and showed high solubility. Unlike commercial products, it showed a 100% dissolution rate. The R-C-P complex formulation secured high RIV solubility and 100% release regardless of pH.Conclusion: The results imply that high-dose RIV can be administered regardless of the meal, reducing the risk of changing the drug effect due to the patient’s administration mistake.Keywords: rivaroxaban, drug-cyclodextrin-polymer triple complex, solubilization, design of experiment

Dan Wang,1 Shannon L Merkle,2 Jennifer E Lee,3,4 Kathleen A Sluka,1 Barbara Rakel,4 Thomas Graven-Nielsen,5 Laura A Frey-Law1 1Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; 2United States Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA; 3Department of Psychology, Mount Mercy University, Cedar Rapids, IA, USA; 4College of Nursing, University of Iowa, Iowa City, IA, USA; 5Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Aalborg, DenmarkCorrespondence: Laura A Frey-LawDepartment of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, 1-252 Medical Education Bldg., 500 Newton Road, University of Iowa, Iowa City, IA 52242, USATel +1 319-335-9804Fax +1 319-335-9707Email laura-freylaw@uiowa.eduPurpose: Some individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS preferentially relates to pain measures which reflect central influences (eg, dynamic quantitative sensory testing (QST) or referred pain), or whether the MSS-pain relationship requires priming from chronic pain, is unknown. Thus, this cross-sectional study investigated the relationships between MSS assessed in a pain-free state and evoked pain sensitivity.Methods: Experimental intramuscular infusion pain and multiple static and dynamic QST were assessed in 465 healthy, pain-free adults: pain thresholds using pressure (PPTs) and heat (HPTs), temporal summation of pain (TSP) using pressure, heat or punctate stimuli, and conditioned pain modulation (CPM) using pressure or heat test stimuli. MSS was assessed using 7 items from Barsky’s Somatosensory Amplification Scale. Differences in pain and QST between sex-specific MSS quartiles were assessed, adjusting for multiple comparisons. All participants completed at least one intramuscular infusion condition, but not all were asked to complete each QST (n=166-465).Results: Both static and dynamic QST differed between highest and lowest MSS quartiles using pressure stimuli: lower PPTs (adjusted-p< 0.01); increased pressure TSP (adjusted-p=0.02); lower pressure CPM (adjusted-p=0.01). However, none of the heat or punctate QST measures (HPTs, TSP, or CPM) differed between MSS quartiles (adjusted-p> 0.05). Odds of experiencing TSP or referred pain was not greater, whereas CPM was 8-fold less likely, in those with highest MSS.Conclusion: Normal variation in non-noxious MSS is related to both static and dynamic pain sensitivity, without sensitization associated with chronic pain, but is dependent on the QST stimulus. Thus, common influences on MSS and pain sensitivity may involve central mechanisms but are likely more complex than previously recognized.Keywords: pain sensitivity, somatosensory amplification scale, experimental muscle pain, quantitative sensory testing, temporal summation of pain, conditioned pain modulation

Ji-Eun Lee,1 Se Young Kim,2 Jae-Ho Yoo,3 Il Tae Hwang,4 Jung Sub Lim,5 Kyung Hee Yi,6 Young-Jun Rhie,7 Gyung Min Lee,8 Hyo-Kyoung Nam,9 Hyun Wook Chae,10 Eun Young Kim,11 Chong Kun Cheon,12 Jieun Lee,13 Young Suk Shim,14 YuJin Lee,15 Eun Young Kim,15 Jin Soon Hwang16 1Department of Pediatrics, Inha University Hospital, Inha University Graduate School of Medicine, Incheon, Republic of Korea; 2Department of Pediatrics & Adolescent Medicine, Bundang Jeseang General Hospital, Daejin Medical Center, Seongnam, Republic of Korea; 3Department of Pediatrics, Dong-a University Hospital, Dong-a University College of Medicine, Busan, Republic of Korea; 4Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University, College of Medicine, Seoul, Republic of Korea; 5Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Republic of Korea; 6Department of Pediatrics, Wonkwang University Sanbon Medical Center, Gunpo, Republic of Korea; 7Department of Pediatrics, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea; 8Department of Pediatrics, Konyang University Hospital, Daejeon, Republic of Korea; 9Department of Pediatrics, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 10Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 11Department of Pediatrics, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea; 12Department of Pediatrics, Pusan National University Children’s Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea; 13Department of Pediatrics, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea; 14Department of Pediatrics & Adolescent Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea; 15Life Sciences, LG Chem, Ltd., Seoul, Republic of Korea; 16Department of Pediatrics & Adolescent Medicine, Ajou University Hospital, Ajou University School of Medicine, Suwon, Republic of KoreaCorrespondence: Jin Soon HwangDepartment of Pediatrics & Adolescent Medicine, Ajou University Hospital, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 16499, Republic of KoreaTel +82 31 219 5166Fax +82 31 219 5169Email pedhwang@ajou.ac.krPurpose: To assess the usability and safety of the disposable pen compared to those of reusable devices in patients receiving recombinant human growth hormone (rhGH) treatment.Patients and methods: This study was a multicenter, single-arm, open-label, switch-over, prospective, Phase IV trial. After screening, eligible patients who were previously treated with rhGH using a reusable device were enrolled to receive treatment with the disposable pen for 8 weeks. The ease of use, preference, and tolerability of the disposable pen compared to those of the reusable device were assessed by the subjects and/or their caregivers using a questionnaire. Adverse events were evaluated by the investigators.Results: Of 116 subjects enrolled in this study, 115 received treatment with the disposable pen and 109 completed the study. The mean age of the subjects was 9.4 years. Compared to the previous reusable device, the disposable pen was assessed as significantly easier to use (mean value 7.88, 95% confidence interval (CI) [7.45–8.30] on a numerical scale ranging from 0 (far less easy) to 10 (far easier)). Furthermore, the percentage of subjects who preferred the disposable pen to the previously used reusable device was 75.7% (95% CI [67.6%–83.8%]). The percentages of subjects who rated pain and discomfort at the injection site as “not at all” were higher after using the disposable pen compared to the reusable device. No specific safety concerns were identified.Conclusion: The disposable pen is easier to use than the reusable devices and is preferred by approximately 75% of patients receiving rhGH treatment. Moreover, the disposable pen is safe and acceptable. Therefore, it could be a good alternative to reusable devices. The disposable pen is expected to provide benefits to patients receiving rhGH treatment.Clinicaltrials.gov identifier: NCT03015909.Keywords: growth hormone, disposable equipment, patient preference, usability, safety

Sun Ho Park,1,2 Sang Cheol Yang,1,2 Jae Jung Lee,1,2 Hanjo Kwon,1,2 Sung Who Park,1,2 Ji Eun Lee1,2 1Department of Ophthalmology, School of Medicine, Pusan National University, Yangsan, South Korea; 2Biomedical Research Institute, Pusan National University Hospital, Busan, South KoreaCorrespondence: Jae Jung LeeDepartment of Ophthalmology, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, South KoreaTel +82-51-240-7957Email jlee@pusan.ac.krPurpose: To investigate the efficacy of fortified barrier laser (FBL) on the vitreous base in vitrectomy for rhegmatogenous retinal detachment (RRD).Patients and methods: This was a retrospective study of patients who underwent vitrectomy for RRD without proliferative vitreoretinopathy. Barrier laser was applied as 3–4 rows surrounding the break at the end of fluid-air exchange. For the FBL, 3–4 rows of laser burn were additionally made about 0.5 clock-hour long adjacent to the break along the posterior border of the vitreous base. The primary outcome was single surgery success rate (SSSR) between two groups: FBL and conventional barrier laser (CBL) groups.Results: Overall, 118 eyes were included; 50 eyes in the FBL group and 68 eyes in the CBL group. SSSR was 100% (50/50) in the FBL group and 91.2% (62/68) in the CBL group with a significant difference (p=0.038). Four eyes of the recurrent cases in the CBL group were related to reopening of the break. All eyes achieved reattachment, and no differences were found in postoperative visual acuity at 6 months.Conclusion: FBL on the vitreous base was efficacious in improving the anatomical success rate of vitrectomy.Keywords: fortified barrier laser, vitreous base, rhegmatogenous retinal detachment, single surgery success rate, vitrectomy

Moon SU, Kim J, Bokara KK, et al. Int J Nanomedicine. 2012;7:2751– 2765. The authors have advised Figure 5 on page 2760 is incorrect. Due to an error at the time of figure assembly the images for Figure 5B and 5F were duplicated. The authors did not pick this error up during the proof-reading stage of the publication. The correct Figure 5 is shown in Download Article. Figure 5 Doublecortin and bromodeoxyuridine staining was performed to detect the migrating exogenous subventricular zone neural progenitor cells in the hydrophilic or hydrophobic carbon nanotubes transplantation groups (A and D) 3 weeks or (E and H) 5 weeks after middle cerebral artery occlusion injury. The images show (A and E) the experimental control group (without subventricular zone neural progenitor cell transplantation), (B and F) injury-subjected rats transplanted with subventricular zone neural progenitor cells, (C and G) injury-subjected rats transplanted with hydrophilic carbon nanotubes impregnated with subventricular zone neural progenitor cells, and (D and H) injury-subjected rats transplanted with hydrophobic carbon nanotubes impregnated with subventricular zone neural progenitor cells. Notes: Doublecortin and bromodeoxyuridine double positive immunostained cells are indicated by yellow. Scale bars = 50 µm.Abbreviations: BrdU, bromodeoxyuridine; DAPI, 4′,6-diamidino-2-phenylindole; DCX, doublecortin. The authors apologize for this error and advise that this does not affect the results of the paper. Read the original article

Sung Who Park,1,2 Jae Jung Lee,1,2 Ji Eun Lee1,2 1Department of Ophthalmology, School of Medicine, Pusan National University, Yangsan, South Korea; 2Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea Abstract: Although the technique of pars plana vitrectomy (PPV) develops rapidly, scleral buckling (SB) has several advantages over PPV for rhegmatogenous retinal detachment (RRD), including early visual rehabilitation and prevention of cataract progression. It is recommended to select the primary procedure for RRD by considering the advantages and disadvantages of each procedure based on the patient status. The vitreous body status affects the features of RRD. Vitreous liquefaction is an age-dependent process, resulting in the development of posterior vitreous detachment (PVD). RRD is usually associated with PVD, typically presenting with a retinal tear, strong vitreoretinal traction, and bullous detachment. In contrast, RRD may develop without PVD, and typically presents with a small atrophic hole, shallow detachment, and slow progression. RRD with less liquefied vitreous and no PVD can be managed successfully with SB alone even in the presence of subretinal strand as less liquefied vitreous acts as bio-tamponade blocking fluid passage. The strong traction induced by PVD and bullous detachment in an eye with extensively liquefied vitreous reduces the success rate of SB. PPV is gaining popularity as the primary procedure for RRD, especially in eyes with retinal tears, PVD, or pseudophakia. Nevertheless, SB remains the preferred procedure in young phakic patients without PVD. Keywords: age, myopia, posterior vitreous detachment, rhegmatogenous retinal detachment, scleral buckling, vitreous

Jung Eun Lee,1,* Koung Li Kim,2,* Danbi Kim,2 Yeongju Yeo,2 Hyounkoo Han,3 Myung Goo Kim,1,4 Sun Hwa Kim,4 Hyuncheol Kim,3,5 Ji Hoon Jeong,1,4 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, 3Department of Chemical and Biomolecular Engineering, Sogang University, 4Center for Theragnosis Biomedical Research Institute, Korea Institute of Science and Technology (KIST), 5Department of Biomedical Engineering, Sogang University, Seoul, Korea *These authors contributed equally to this work Abstract: Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders. Keywords: apatinib, corneal neovascularization, nanoparticle, vascular endothelial growth factor

Seung Yeon Son,1 Hye Ryoun Jang,1 Jung Eun Lee,1 Heejin Yoo,2 Kyunga Kim,2,3 Jae Berm Park,4 Sung Joo Kim,4 Ha Young Oh,1 Wooseong Huh1 1Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 2Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, 3Department of Digital Health, SAIHST, 4Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Abstract: This study aimed to evaluate the long-term efficacy and safety of a generic tacrolimus (Tacrobell [TCB]) compared to the original tacrolimus (Prograf [PGF]) in kidney transplant recipients. In this retrospective observational study, we analyzed the data from 444 patients who took TCB as a first-line immunosuppressive drug and 245 patients who took PGF. The 5-year graft survival rate was 92% for patients in the PGF group and 97% for patients in the TCB group, respectively. Cox proportional hazards for a one-sided, noninferiority model showed noninferiority (upper confidence interval [CI] limit of the hazard ratio [HR]

Ji Eun Lee,1 Dong Wook Shin,1–3 Beomseok Suh,1 Sohyun Chun,4 You-Seon Nam,3 Belong Cho1,2 1Department of Family Medicine, Health Promotion Center, 2Laboratory of Health Promotion and Health Behavior, Biomedical Research Institute, Seoul National University Hospital, 3JW Lee Center for Global Medicine, Seoul National University College of Medicine, 4International Health Services, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea Introduction: In Asian countries, reluctance to seek pharmacological intervention is a major barrier for smoking cessation. Culturally appropriate decision aids are expected to help people in the decision making for the use of smoking cessation medication. Objective: The aim of this study was to develop a culturally tailored decision aid for smoking cessation and evaluate its effect on the use of smoking cessation medication. Patients and methods: A 7-minute video on smoking cessation information and options was developed. Physicians were randomized into intervention and control groups. The decision aid was provided to patients in the intervention group, and they watched it, while those in the control group were provided usual medical care for smoking cessation. The primary outcome was the proportion of smokers who were prescribed smoking cessation medication within 1 month after consultation. The secondary outcomes were abstinence rate and use of smoking cessation medication within 6 months. A logistic regression analysis was used to assess the effect of the decision aid on the outcomes. Results: In total, 414 current smokers (intervention group: 195; control group: 219) were enrolled. The mean age of the participants was 48.2 years, and 381 subjects (92%) were males. In total, 11.8% of the participants in the intervention group and 10.5% in the control group were prescribed smoking cessation medications within 1 month. The odds ratio was 1.02 (95% CI: 0.40–2.63) after adjustment for baseline characteristics. Within 6 months, 17.4% of the participants in the intervention group and 15% in the control group were prescribed medication (adjusted odds ratio 1.12, 95% CI: 0.59–2.13). Conclusion: The culturally tailored smoking cessation decision aid developed in this study did not show a significant impact on the decision to use smoking cessation medication. Further research to develop more effective and more interactive interventions is expected. Keywords: smoking, clustered randomized trial, decision aids, Korea

Ji Hoon Jeong,1,* Hong Khanh Nguyen,2,* Jung Eun Lee,1 Wonhee Suh2 1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Chung-Ang University, Seoul, Korea *These authors contributed equally to this work Abstract: Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood–retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. Keywords: permeability, retinal vascular endothelial cells, vascular endothelial growth factor

Ji-Hye Byun,1 Sun-Hong Kwon,1 Ji-Eun Lee,1 Ji-Eun Cheon,1 Eun-Jin Jang,2 Eui-Kyung Lee1 1School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 2Information Statistics, Andong National University, Andong, Gyeongsangbuk-do, South Korea Purpose: To elucidate and compare benefit–risk preferences among Korean patients and physicians concerning cyclooxygenase-2 (Cox-2) inhibitor treatments for arthritis.Materials and methods: Subjects included 100 patients with arthritis and 60 board-certified orthopedic surgeon physicians in South Korea. Through a systematic review of the literature, beneficial attributes of using Cox-2 inhibitors were defined as a decrease in the Western Ontario and McMaster Universities Arthritis Index for pain score and improvement in physical function. Likewise, risk attributes included upper gastrointestinal (GI) complications and cardiovascular (CV) adverse events. Discrete choice experiments were used to determine preferences for these four attributes among Korean patients and physicians. Relative importance and maximum acceptable risk for improving beneficial attributes were assessed by analyzing the results of the discrete choice experiment by using a conditional logit model.Results: Patients ranked the relative importance of benefit–risk attributes as follows: pain reduction (35.2%); physical function improvement (30.0%); fewer CV adverse events (21.5%); fewer GI complications (13.4%). The physicians’ ranking for the same attributes was as follows: fewer CV (33.5%); pain reduction (32.4%); fewer GI complications (18.1%); physical function improvement (16.0%). Patients were more willing than physicians to accept risks when pain improved from 20% or 45% to 55% and physical function improved from 15% or 35% to 45%.Conclusion: We confirmed that patients and physicians had different benefit–risk preferences regarding Cox-2 inhibitors. Patients with arthritis prioritized the benefits of Cox-2 inhibitors over the risks; moreover, in comparison with the physicians, arthritis patients were more willing to accept the trade-off between benefits and risks to achieve the best treatment level. To reduce the preference gap and achieve treatment goals, physicians must better understand their patients’ preferences. Keywords: discrete choice experiment, Cox-2 inhibitors, willingness to accept, patient and physicians preference, arthritis

Jung Eun Lee,1,2 In Young Jo,3 Song Mi Lee,3 Woo Jeong Kim,3 Hoon Young Choi,2,4 Sung Kyu Ha,4 Hyung Jong Kim,5 Hyeong Cheon Park2,4 1Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 2Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, 3Department of Nutrition Services, Gangnam Severance Hospital, 4Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 5Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea Background: The number of elderly people on dialysis is increasing rapidly. Fluid overload and malnutrition status are serious problems in elderly dialysis patients. We aimed to compare the hydration and nutritional status through bioimpedance analysis (BIA) between young and elderly hemodialysis (HD) patients and to analyze risk factors related to fluid overload and malnutrition status in these patients.Method: We conducted a cross-sectional study, in which 82 HD (males 42, mean age 58.7±12.9 years) patients were enrolled. We collected different types of data: laboratory data, such as serum creatinine, albumin, total iron-binding capacity, hemoglobin, total cholesterol; anthropometric data, such as hand grip strength (HGS); BIA data, such as intracellular water, skeletal muscle mass, body cell mass, bone mineral content, phase angle (PhA), extra cellular water (ECW)/total body water (TBW) ratio; and malnutrition-inflammation score (MIS), which is a traditional nutritional parameter for dialysis patients. All patients were stratified into two groups according to their age: young (

Hyunjeong Baek,1,* Seunghoon Han,2,3,* Dong-Seok Yim,2,3 Sung Joo Kim,4 Soo-Youn Lee,5 Hye Ryoun Jang,6 Jung Eun Lee,6 Dae Joong Kim,6 Yoon-Goo Kim,6 Ha Young Oh,6 Wooseong Huh6 1Department of Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea; 2Department of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 3PIPET (Pharmacometrics Institute for Practical Education and Training), Seoul, Republic of Korea; 4Department of Surgery, 5Department of Laboratory Medicine and Genetics, 6Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea *These authors equally contributed to this work Abstract: This study aimed to evaluate the change in the pharmacokinetics (PK) of cyclosporine in the non-steady-state period in the first week after renal transplantation; the factors influencing this change, including genetic variability; and the time point concentration that correlated best with drug exposure. Data were obtained from 69 patients, and PK studies were conducted on postoperative days (PODs) 2, 3, and 7. Samples were taken pre-dose and at 1, 2, 3, 4, 6, 8, and 12 hours after drug administration. MDR1, CYP3A4, and CYP3A5 were genotyped. A population PK analysis and correlational analysis between the concentration at each time point and the area under the time–concentration curve were performed. A two-compartment model with first-order absorption was chosen. The rate and extent of drug absorption showed a significant increase on POD3, followed by a slight decrease on POD7. Until POD3, 8 hours post-dose was the single time point concentration that correlated best with drug exposure and 3 hours was the best time point on POD7. In both analyses, the MDR1 genotype showed potential as a factor influencing PK change. We conclude that oral administration of cyclosporine and dose adjustment based on a single concentration measurement might result in unexpected drug exposure during this early posttransplantation period. Keywords: renal transplantation, multidrug resistance 1 (MDR1) gene, cytochrome P450

The development of new treatment agents in recent decades has significantly improved the survival of patients with multiple myeloma (MM). Nonetheless, MM remains an incurable disease; therefore, novel combination therapies are required. Natural killer (NK) cells are one of the safest immunotherapeutic options. In this study, we found that the anti-myeloma activity of expanded NK cells (eNKs) was improved by daratumumab, lenalidomide, and dexamethasone (DRd) in an MM xenograft mouse model. NK cells expanded from peripheral blood mononuclear cells collected from MM patients were highly cytotoxic against DRd pretreated tumor cells in vitro. To mimic the clinical protocol, a human MM xenograft model was developed using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull (NSG) mice. MM bearing mice were randomly divided into six groups: no treatment, eNK, Rd, Rd + eNKs, DRd, and DRd + eNKs. DRd significantly enhanced the cytotoxicity of eNKs by upregulating NK cell activation ligands and effector function. DRd in combination with eNKs significantly reduced the serum M-protein level and prolonged mouse survival. In addition, DRd significantly increased the persistence of eNK and homing to MM sites. These results show that the anti-myeloma activity of ex vivo-expanded and activated NK cells is augmented by the immunomodulatory effect of DRd in MM-bearing mice, suggesting the therapeutic potential of this combination for MM patients.

Sung Who Park,1 Ik Soo Byon,1 Hyun Jun Park,2 Ji Eun Lee,1,3 Boo Sup Oum1,31Department of Ophthalmology, School of Medicine, Pusan National University, Busan, Korea; 2Department of Ophthalmology, Yangsan Pusan National University Hospital, Busan, Korea; 3Medical Research Institute, School of Medicine, Pusan National University Hospital, Busan, KoreaAbstract: The aim of this study was to report a case of acute retinal necrosis (ARN) after intraocular foreign body removal. A 32-year-old male presented with visual loss in the left eye. He was hit by an iron fragment while he was hammering. An intraocular foreign body was found with corneal laceration and traumatic cataract. On the day he was injured, primary closure of the laceration, lensectomy, and vitrectomy were performed, and the foreign body was removed. The day after the operation, there was no sign of retinal detachment or retinitis. Two days after the operation, retinal necrosis and accompanying vitreous inflammation were noted in the far periphery. On day 3, the necrosis spread circumferentially and inflammation became more distinct. ARN was presumed and intravenous acyclovir was administered. The necrotic areas were reduced 2 days later, and were resolved in 1 month. The final visual acuity in his left eye was 20/20 after implantation of an intraocular lens. This case is the first report of ARN after penetrating injury and an intraocular foreign body. ARN may develop after open-globe injury.Keywords: necrotizing herpetic retinopathy, acute retinal necrosis, intraocular foreign body

Joo Eun LeeDepartment of Ophthalmology, Inje University College of Medicine, Busan, South KoreaPurpose: To report the results of a two-step operation for treating retinal detachments caused by macular holes in high-myopic patients.Methods: In the first part of the operation, pars plana vitrectomy, air–fluid exchange, and silicone oil injection were performed. At 4–6 months after the first operation, the second part of the operation was performed. This involved silicone oil removal and internal limiting membrane peeling under the aid of triamcinolone acetonide with or without gas tamponade.Results: Four eyes (four patients) underwent surgery with this technique. All retinas were attached at the time of the second operation, when internal limiting membrane peeling could be performed easily and safely. The retina remained attached in all four eyes (100%) during 24–32 months of follow-up after the second operation.Conclusion: Favorable surgical results were obtained with the two-step operation in the treatment of retinal detachments resulting from myopic macular holes.Keywords: internal limiting membrane peeling, macular hole, macular hole retinal detachment, retinal detachment, silicone oil, two-step

Joo Eun LeeDepartment of Ophthalmology, Inje University College of Medicine, Busan, South KoreaObjective: To describe an optic capture pars plana lensectomy technique.Methods: After core vitrectomy, pars plana lensectomy is performed with preservation of the anterior capsule. Capsulorhexis is performed on the preserved anterior capsule through a 2.8 mm clear corneal incision. An intraocular lens (IOL) is placed in the ciliary sulcus, and then the optic of the IOL is pushed back to the vitreous cavity so that the optic is captured by the surrounding capsulorhexis margin.Results: The captured IOL-capsule diaphragm remained stable during air–fluid exchange and prevented air prolapse to the anterior chamber. IOL stability and a clear visual axis were preserved during the follow-up period.Conclusion: With this modified pars plana lensectomy technique, stable IOL position and clear visual axis can be maintained when a pars plana approach is needed during combined cataract and vitreoretinal surgery.Keywords: lensectomy, optic capture, pars plana lensectomy, vitrectomy

Ha Na Oh,1 Joo Eun Lee,2 Hyun Woong Kim,1 Jae Wook Yang,1 Il Han Yun11Department of Ophthalmology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea; 2Department of Ophthalmology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, KoreaPurpose: To report on a case that developed an atypical form of occult choroidal neovascularization (CNV) after successful macular hole surgery.Methods: Visual acuity change, color fundus photographs, fluorescein and indocyanine green angiograms, and optical coherence tomography results were compared throughout the follow-up duration.Patients: A 64-year-old woman with a macular hole in the right eye and drusen in both eyes underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. One month after the operation she developed occult CNV, in which pigment epithelial detachment and fine retinal pigment epithelial (RPE) layer wrinkles were observed under the completely sealed macular hole. After 3-monthly intravitreal injections of ranibizumab, the lesion did not change significantly.Conclusion: CNV can develop after otherwise successful macular hole surgery, especially in patients with pre-existing aging changes in the macula, such as drusen. Care should be taken in such patients, to prevent the development of CNV after macular hole surgery.Keywords: drusen, macular hole surgery, occult choroidal neovascularization, ranimizumab injection

Sung Ung Moon,1,* Jihee Kim,1,2,* Kiran Kumar Bokara,1,* Jong Youl Kim,1 Dongwoo Khang,3,4 Thomas J Webster,3,4 Jong Eun Lee1,21Department of Anatomy, 2Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; 3School of Engineering, 4Department of Orthopedics, Brown University, Providence, RI, USA*These authors contributed equally to this workAbstract: The present in vivo study was conducted to evaluate whether hydrophilic (HL) or hydrophobic (HP) carbon nanotubes (CNTs) impregnated with subventricular zone neural progenitor cells (SVZ NPCs) could repair damaged neural tissue following stroke. For this purpose, stroke damaged rats were transplanted with HL CNT-SVZ NPCs, HP CNT-SVZ NPCs, or SVZ NPCs alone for 1, 3, 5, and 8 weeks. Results showed that the HP CNT-SVZ NPC transplants improved rat behavior and reduced infarct cyst volume and infarct cyst area compared with the experimental control and the HL CNT-SVZ NPC and SVZ NPCs alone groups. The transplantation groups showed an increase in the expression of nestin (cell stemness marker) and proliferation which was evident with the increased number of doublecortin and bromodeoxyuridine double-stained immunopositive cells around the lesion site. But, these effects were more prominent in the HP CNT-SVZ NPC group compared with the other transplantation groups. The HP CNT-SVZ NPC and HL CNT-SVZ NPC transplants increased the number of microtubule-associated protein 2 (marker for neurons) and decreased the number of glial fibrillary acidic protein (marker for astroglial cells) positive cells within the injury epicenter. The majority of the transplanted HP CNT-SVZ NPCs collectively broadened around the ischemic injured region and the SVZ NPCs differentiated into mature neurons, attained the synapse morphology (TUJ1, synaptophysin), and decreased microglial activation (CD11b/c [OX-42]). For these reasons, this study provided the first evidence that CNTs can improve stem cell differentiation to heal stroke damage and, thus, deserve further attention.Keywords: biocompatibility, brain, in vivo, stem cell, wettability, carbon nanotubes, stroke

Valerie Montgomery Rice,1 Margaret C Maimbolwa,2 Esther Munalula Nkandu,2 Jacqueline Fleming Hampton,3,* Jae-Eun Lee,4 James EK Hildreth51Morehouse School of Medicine, Atlanta, GA, USA; 2School of Medicine, University of Zambia, Lusaka, Zambia; 3Meharry Medical College, Center for AIDS Health Disparities Research, Nashville, TN, USA; 4RCMI Translational Research Network Data and Technology Coordinating Center, Jackson State University, Jackson, MS, USA; 5Dean, College of Biological Sciences, University of California Davis, Davis, CA, USANote: at the time the research was conducted, Dr Montgomery Rice was the Executive Director, Center for Women's Health Research, Meharry Medical College, Nashville, TN, USA, and Dr Hildreth was the Director, Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN*Dr Fleming Hampton has passed away since this manuscript was written. We wish to honor her memory by including her as an authorPurpose: We sought to determine the relationship between acceptability of a hypothetical vaginal microbicide, cultural factors, and perceived HIV risk among African-American women in Nashville, TN, USA, and African women in Kafue and Mumbwa, Zambia.Patients and methods: Women in both sites completed a survey. Regression analyses were performed on valid samples (Nashville, 164; Zambia, 101) to determine cultural differences affecting microbicide acceptability. Regression analyses also tested whether individual risk perception affected acceptability.Results: In Zambia, 89.6% of women were willing to use a microbicide versus 81.6% in Nashville (P < 0.0001). One cultural difference is that women in the Zambian cohort viewed risk of HIV infection as distinct from risk of acquiring STIs, with 48% believing they were certain to become infected with AIDS, compared to 4% of Nashville participants.Conclusion: These results suggest a high degree of acceptability toward use of a vaginal microbicide to prevent HIV infection.Keywords: HIV/AIDS, women, birth control, sexually transmitted infections

Sunhyae Jang1,*, Ji Won Park2,*, Hye Rim Cha1, Sun Young Jung1, Jeong Eun Lee1, Sung Soo Jung1, Ju Ock Kim1, Sun Young Kim1, Choong Sik Lee3, Hee Sun Park1 1Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Medical School, Daejeon, 2Division of Pulmonology, Department of Internal Medicine, Daejeon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, 3Department of Pathology, Chungnam National University Medical School, Daejeon, South Korea*These authors contributed equally to this workAbstract: The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.Keywords: allergic airway disease, hypoxia inducible factor-1α, vascular endothelial growth factor

Ik Soo Byon1, Ji Hun Kim1, Ji Eun Lee1,2, Boo Sup Oum1,2 1Department of Ophthalmology, Pusan National University Hospital; 2Medical Institute, School of Medicine, Pusan National University, Busan, Republic of Korea Abstract: The authors report two cases of rebound phenomenon treated with intravitreal triamcinolone acetonide in Vogt-Koyanagi-Harada (VKH) disease. Patients in the acute phase of VKH disease were treated with high-dose intravenous (IV) methylprednisolone (1 g/day) for 3 days. Serous retinal detachment decreased and visual acuity improved during IV steroid treatment. After switching to oral steroid treatment, choroiditis and visual acuity worsened. An injection of triamcinolone acetonide (4 mg) into the vitreous resulted in gradual resolution of subretinal fluid and improvement of visual acuity. Systemic steroids were tapered to discontinuation without a relapse of inflammation. Adjuvant intravitreal triamcinolone is useful in the management of the rebound phenomenon in VKH disease. Keywords: adjuvant intravitreal steroid, serous retinal detachment, visual acuity, choroiditis

This paper describes the design and investigation of a high-school-affiliated esports program based on an enrichment learning model. In it, the authors detail the connections between esports and learning, self-reported impacts of the program and demographic differences among them, students' attitudes toward program features, and equity in results across demographic groups. Several methods over four years were used to document and evaluate the program including observational fieldwork, an online retrospective posttest survey, and a modified instrument given in an alternative one-sample pretest-posttest design. Authors find compelling evidence that an enrichment approach to youth esports yields positive outcomes in communication, social-emotional skills, and school affiliation. There are also indications that this approach temporarily staved off an overall downward trend in key variables including STEM interest, self-regulation, attendance, and GPA, during the COVID-19 global pandemic.

Dendritic cells (DCs) are the most potent antigen-presenting cells, and have thus been used in clinical cancer vaccines. However, the effects of DC vaccines are still limited, leading researchers to explore novel ways to make them effective. In this study, we investigated whether human monocyte-derived DCs generated via the addition of interleukin 15 (IL-15) had a higher capacity to induce antigen-specific T cells compared to conventional DCs. We isolated CD14+ monocytes from peripheral blood from multiple myeloma (MM) patients, and induced immature DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 in the presence or absence of IL-15 for 4-6 days. Then we generated mature DCs (mDCs) with lipopolysaccharide for another 2 days [IL-15 mDCs (6 days), IL-15 mDCs (8 days), and conventional mDCs (8 days)]. IL-15 mDCs (6 days) showed higher expression of MHC I and II, CD40, CD86, and CCR7, and the secretion of IFN-γ was significantly higher compared to conventional mDCs. IL-15 mDCs (6 days) showed superior polarization of naïve T cells toward Th1 cells and a higher proportion of activated T cells, cytokine-induced killer (CIK) cells, and natural killer (NK) cells for inducing strong cytotoxicity against myeloma cells, and lower proportion of regulatory T cells compared to conventional mDCs. These data imply that novel multipotent mDCs generated by the addition of IL-15, which can be cultivated in 6 days, resulted in outstanding activation of T cells, CIK cells and NK cells, and may facilitate cellular immunotherapy for cancer patients.

A crisis of literacy has emerged among high school students in the United States. In order to encourage students' engagement with literacy education, there is a need for an integrated curriculum of English Language Arts (ELA). An integrated language arts curriculum would allow students to learn literacy and reading skills while engaging with a motivating context. Meanwhile, esports has grown as a worldwide culture, expanding to more than just players and spectators to include a whole ecosystem of stakeholders. As esports grow in popularity and acceptance, educators have looked to connect the skills developed in esports with academic and career opportunities. We found esports to be a viable content area for the integrated curriculum because esports is favored among many students and involves reading activity as an essential part of participation. In this paper, we present the development of the first high school integrated curriculum that uses esports as its main content. Over two years, we developed the first high school curriculum that integrated esports as its main content. Spanning four years, the curriculum melds ELA standards, Science, Technology, Engineering and Mathematics (STEM) practices, career-technical education (CTE), and social-emotional learning (SEL) under the umbrella of esports. For each step, we present the rationale in the design process, and challenges have arisen during the curriculum design process. We detail how the curriculum ties each set of standards together and report on first implementation efforts. Additionally, we present how teacher feedback and student workshops led to the design of club toolkits, supplemental material for teachers and school clubs.