Search

Amber N Piazza,1 Peter A Downie,1,2 Michael S Lee,3 Bruce R Lindgren,4 Joshua H Olson3 1Medical School, University of Minnesota, Minneapolis, MN, 55455, USA; 2Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, WI, 53226, USA; 3Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, 55455, USA; 4Masonic Cancer Center Biostatistics Core, University of Minnesota, Minneapolis, MN, 55455, USACorrespondence: Joshua H Olson, Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 516 Delaware St SE, MMC 493, Minneapolis, MN, 55455, USA, Tel +1-612-625-4400, Fax +1-612-626-7882, Email olso3675@umn.edBackground: Millions of acute conjunctivitis cases occur in the United States annually. The impact of COVID-19 mitigation practices on viral conjunctivitis incidence within ophthalmology clinics has not been reported. We hypothesized that viral conjunctivitis rates would decrease with implementation of such practices.Methods: A retrospective chart review was conducted at a single academic center’s ophthalmology clinics. Electronic health record data was queried using ICD-10 diagnostic codes to include 649 patients aged 2– 97 with viral, bacterial, or allergic conjunctivitis diagnosed either before (6/1/2018– 5/1/2019) or during (6/1/2020– 5/1/2021) COVID-19 precautions. Conjunctivitis rates per ophthalmology clinic visit were compared using rate-ratio analysis. Logistic regression evaluated the effects of age, sex, and race among those with conjunctivitis.Results: A total of 66,027 ophthalmology clinic visits occurred during the study period. Viral conjunctivitis rates per visit did not significantly change after enacting COVID-19 mitigation strategies, but allergic conjunctivitis rates significantly increased (viral: RR 0.82, 95% CI 0.51 to 1.31, p=0.408; allergic: RR 1.70, 95% CI 1.43 to 2.03, p< 0.001). When controlling for time, younger age (≤ median age 55) (p=0.005) and Caucasian race (p=0.009) were associated with higher viral conjunctivitis frequency.Conclusion: Contrary to trends reported in emergency departments, viral conjunctivitis rates within an ophthalmology clinic did not significantly change after COVID-19 mitigation strategies, though allergic conjunctivitis rates increased. Patients’ avoidance of emergency departments during the pandemic may have contributed. Further investigation is required to explore variation in ophthalmology patient populations and needs based on care setting.Plain Language Summary: A retrospective review included 649 patients with viral, bacterial, or allergic conjunctivitis diagnosed at a single center’s ophthalmology clinics before (6/1/2018– 5/1/2019) or during (6/1/2020– 5/1/2021) COVID-19 precautions. Contrary to emergency department experiences, viral conjunctivitis rates did not significantly change after COVID-19 precautions. However, allergic conjunctivitis rates significantly increased. Conjunctivitis presentation in ophthalmology clinics differed from that reported in emergency departments, warranting further evaluation of variation in patient needs by setting.Keywords: viral conjunctivitis, allergic conjunctivitis, conjunctivitis transmission, COVID-19, COVID-19 precautions

Sang-Jin Park,1,&ast; Seung Ro Han,2,3,&ast; Yun Hee Kang,2,3,&ast; Eun-Jin Lee,1 Eu-Gene Kim,1 Hyobong Hong,4 Jae-Chan Jeong,4 Myung-Shin Lee,2,3 Seung-Hoon Lee,2,5 Dae-Yong Song1 1Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea; 2Eulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, Korea; 3Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, Korea; 4Artifcial Intelligence Research Laboratory, Electronics and Telecommunications Research Institute (ETRI), Daejeon, Korea; 5Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea&ast;These authors contributed equally to this workCorrespondence: Seung-Hoon Lee, Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea, Tel +82-42-259-1612, Fax +82-42-259-1669, Email nslsh@eulji.ac.kr Dae-Yong Song, Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea, Tel +82-42-259-1622, Fax +82-42-259-1669, Email dysong@eulji.ac.krPurpose: Magnetic particle imaging (MPI) is an emerging radiation-free, non-invasive three-dimensional tomographic technology that can visualize the concentrations of superparamagnetic iron oxide nanoparticles (SPIONs). To verify the applicability of the previously proposed point-of-care testing MPI (PoCT-MPI) in medical diagnosis and therapeutics, we imaged SPIONs in animal tumor models.Methods: CT26 or MC38 mouse colon carcinoma cells (2 × 106 cells) were subcutaneously injected into the right flank of BALB/c mice. SPIONs were either injected directly into the tumor lesions in the intratumoral group or through tail veins in the intravenous group. CT26 and MC38 tumor models were examined both intratumorally and intravenously to confirm the biological availability of SPIONs using PoCT-MPI.Results: Signals were observed in the tumor lesions from day 1 to day 7. This is the first study to successfully image the pathological region and show the biodistribution of SPIONs in CT26 tumor models using the recently developed PoCT-MPI technology. Furthermore, MC38 tumor models were examined, resulting in similar images to those of the CT26 tumor model in both intratumoral and intravenous groups.Conclusion: The present study demonstrates the biological applicability of PoCT-MPI, which promises to be a powerful diagnostic and therapeutic technique in biomedical imaging.Keywords: colon cancer, syngeneic mouse tumor model, point-of-care testing MPI, diagnostics

Eunseop Kim,1 Hye Won Lee,2 Namhyoung Kim,1 Young Hee Park,3 Tae-Young Choi,4 Myeong Soo Lee4 1You and Green Korean Medicine Clinic, Daejeon, South Korea; 2KM Convergence Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South Korea; 3You and Green Korean Medicine Clinic, Busan, South Korea; 4KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, South KoreaCorrespondence: Myeong Soo Lee, KM Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, South Korea, Tel +82-42-868-9266, Fax +82-42-868-9299, Email drmslee@gmail.com; mslee@kiom.re.kr Hye Won Lee, KM Convergence Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, South Korea, Tel +82-42-868-9506, Fax +82-42-868-9299, Email hwlee@kiom.re.krPurpose: Few studies have assessed outcomes associated with the use of traditional medicine therapies to manage infertility in clinical practice. The aim of this study was to investigate the clinical characteristics of and infertility treatment effects among patients who visited a Korean medicine (KM) clinic to aid in achieving pregnancy. This study consisted of a 10-year analysis of patient records from a KM clinic.Methods: A retrospective 10-year (2010– 2020) chart analysis was performed using the medical records of infertile patients who visited a KM clinic in South Korea for fertility treatment (ICD-10, infertility symptoms: 59 codes).Results: Of the 6194 patients who visited the clinic during the selected time frame, 1786 were female patients seeking fertility treatment to achieve pregnancy. Among the 1786 infertile women, 586 women succeeded in becoming pregnant (32.8%). Among the 586 patients who became pregnant, 476 women had received KM, 92 had been treated using KM and in vitro fertilization (IVF), and 18 had received KM and undergone intrauterine insemination (IUI). The live birth rates achieved with these treatments were 66.0%, 68.8%, and 66.7%, respectively. The most frequently prescribed medicines were Gamiboher-tang (Jiaweiwuxu-tang), Gamiguibi-tang (Jiaweiguipi-tang), and Gamidanggui-san (Jiaweidanggui-san). Additionally, the most frequent adjunct therapies administered to these patients were acupuncture and moxibustion.Conclusion: Infertility therapies using KM may be a successful option to treat infertility when used alone or in addition to IVF and IUI. However, further pharmacological investigations and clinical trials are required to ensure the objectivity of the efficacy evaluation.Keywords: herbal medicine, infertility, pregnancy, pregnancy rate, fertilization in vitro, retrospective studies

Chang-Hung Kuo,1,2 Mei-Lan Tsai,3 Chung-Hsiang Li,2,4 Hui-Pin Hsiao,4 Mei-Chyn Chao,4 Ming-Sheng Lee,4 Yi-Ching Lin,5– 8 Chih-Hsing Hung3,4,9 1Ta-Kuo Clinic, Kaohsiung, Taiwan; 2Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Laboratory Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Substance and Behavior Addiction Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 9Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, TaiwanCorrespondence: Chih-Hsing HungDepartment of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, No. 482, Shanming Road, Siaogang District, Kaohsiung, 812, TaiwanTel +886-7-3121101-6506Fax +886-7-3213931Email pedhung@gmail.comPurpose: Asthma causes a substantial morbidity and mortality burden in children and the pathogenesis of childhood asthma is not completely understood. Macrophages are heterogeneous with divergent M1/M2 polarization phenotypes in response to various stimulations during the inflammatory process. We aimed to investigate the pattern of macrophage polarization and its association with severity and exacerbation in asthmatic children.Patients and Methods: Normal and asthmatic children aged 4– 18 years were enrolled for 12 months. Children with asthma were further subgrouped according to their severity and the requirement for hospitalization during exacerbations. Clinical data were obtained from medical records. Peripheral blood samples were collected to analyze macrophage polarization, including M1, M2, and subsets, by flow cytometry.Results: Fifty-one asthmatic cases and 27 normal controls were included in this study. The level of PM-2K+CD14+ but not PM-2K+CD14− was decreased in asthmatic children. The levels of M2a (CCR7−CXCR1+), M2b (CCR7−CD86+), and M2c (CCR7−CCR2+) subsets, but not M1 (CCR7+CD86+), were increased in asthmatic children. The levels of M1 were decreased, but the levels of M2c were increased, in children with moderate asthma compared to those with mild asthma. The levels of PM-2K+CD14+ cells and M1 subsets were decreased, but the M2c subset cells were increased in asthmatic children requiring hospitalization during exacerbations.Conclusion: Macrophage polarization may be involved in the pathogenesis of childhood asthma and is a potential biomarker of childhood asthma disease severity.Keywords: M2 macrophage polarization, asthma severity, asthma exacerbation, childhood asthma hospitalization

Ming-Hsueh Tsai,1 Tom C Chan,2 Meng-Sui Lee,3,4 Mei-Shu Lai5 1Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan; 2Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 3Department of Dermatology, Taipei City Hospital, Taipei, Taiwan; 4Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Meng-Sui LeeDepartment of Dermatology, Taipei City Hospital, No. 33, Sec. 2, Zhonghua Road, Taipei, 100, TaiwanTel/Fax +886 2 23889595 Ext 2225Email leemengsui@hotmail.comMei-Shu LaiInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 5Fl. No. 17, Hsu Chow Road, Taipei, 100, TaiwanTel +886 2 33668018Email mslai@ntu.edu.twPurpose: Psoriasis is an inflammatory disease associated with cardiovascular disease. Methotrexate (MTX) is a first-line systemic anti-psoriatic agent that may also protect against cardiovascular disease. We examined the cardiovascular risks among patients with psoriasis who were receiving MTX or the comparator, retinoids.Patients and Methods: We analysed data from the Taiwanese National Health Insurance database. The primary outcome was a composite of hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality (composite cardiovascular outcome). Propensity score-weighted analyses were used to evaluate patients who were followed from therapy initiation to the earliest instance of outcome occurrence, insurance disenrollment, death or study termination.Results: We identified 13,777 patients who received MTX and 6020 patients who received retinoids from 2000 to 2012. Compared to retinoids, MTX was associated with lower crude incidences of cardiovascular outcomes, hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality. In intention-to-treat analyses, MTX was associated with lower risks of composite cardiovascular outcomes (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76– 0.94), ischaemic heart disease (HR: 0.87, 95% CI: 0.71– 1.06), ischaemic stroke (HR: 1.06, 95% CI: 0.89– 1.27) and all-cause mortality (HR: 0.75, 95% CI: 0.66– 0.85). Similar results were found in as-treated analyses.Conclusion: In this nationwide cohort of patients with psoriasis, compared to retinoids, MTX was associated with a modestly lower risk of cardiovascular events.Keywords: cardiovascular events, inflammation, psoriasis, pharmacoepidemiology

Lin Ang,1,2 Hye Won Lee,3 Anna Kim,4 Jun-Yong Choi,5 Myeong Soo Lee1,2 1Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Korea; 2Korean Convergence Medicine, University of Science and Technology, Daejeon, Korea; 3Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea; 4Future Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Korea; 5Pulmonology Division, School of Korean Medicine and Korean Medicine Hospital of Pusan National University, Yangsan, KoreaCorrespondence: Myeong Soo LeeClinical Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, KoreaTel +82-42-868-9266Fax +82-42-868-9299Email drmslee@gmail.comHye Won LeeHerbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, KoreaTel +82-42-868-9506Fax +82-42-868-9299Email hwlee@kiom.re.krPurpose: In this study, we aimed to identify the pattern and combination of herbs used in the formulae recommended for treating different stages of COVID-19 using a network analysis approach.Methods: The herbal formulae recommended by official guidelines for the treatment of COVID-19 are included in the present analysis. To describe the tendency of herbs to form a “herb pair”, we computed the mutual information (MI) value and distance-based mutual information model (DMIM) score. We also performed modularity, degree, betweenness, and closeness centrality analysis. Network analyses were performed and visualized for each disease stage.Results: A total of 142 herbal formulae comprising 416 herbs were analyzed. All possible herbal pairs were examined, and the top frequently used herbal pairs were identified for each disease stage. The herb Glycyrrhizae radix et rhizoma is only identified in one herb pair, even though this herb is identified as one of the herbs with high frequency of use for every disease stage. This suggests that the DMIM score could be used to identify the optimal combination rule of herbal formulae by achieving a balance among the herbs’ frequency and relative distance in herbal formulae.Conclusion: Our results presented the prescription patterns and herbal combinations of the herbal formulae recommended for the treatment of COVID-19. This study may provide new insights and ideas for clinical research in the future.Keywords: coronavirus 19, disease stage, herbs pairing, prescription pattern, network graph

Elevated atmospheric CO2 (eCO2) concentration initially enhances photosynthesis, growth and ecosystem productivity, but the excessive use of nitrogen due to the increased productivity causes uncertainty in long-term ecosystem responses. We exposed Korean red pine, Chinese ash, and Korean mountain ash to current atmospheric CO2 concentration (aCO2), 1.4 times higher CO2 concentration (eCO21.4), and 1.8 times higher CO2 concentration (eCO21.8) in an Open-Top Chamber (OTC) experiment for eight years (2010-2017) to investigate the effect on the morphological and physiological properties of trees. We also assessed whether nitrogen limitation occurred with time by comparing leaf and soil nitrogen concentration. CO2 fertilization effect was observed on tree growth for the first two years (p < 0.05), but there was no difference thereafter. For photosynthetic properties, CO2 effects were species-specific; no effects on Korean red pine and Chinese ash vs. significant effect on Korean mountain ash. However, maximum photosynthetic and carboxylation rates significantly decreased by 24.3% and 31.3% from 2013 to 2017, respectively. Leaf nitrogen significantly decreased by 21.0 % at eCO21.4 and 18.5 % at eCO21.8 compared with aCO2 treatment. This study showed the decline of leaf nitrogen and species-specific responses to long-term high CO2 concentration, which will effect on species competition and ecosystem succession.

Jin Seo Lee,1 Mi Suk Lee,2 Yoonseon Park,3 Jacob Lee,4 Eun-Jeong Joo,5 Joong Sik Eom6 1Division of Infectious Disease, Department of Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 2Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Republic of Korea; 4Division of Infectious Diseases, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea; 5Division of Infectious Diseases, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 6Division of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of KoreaCorrespondence: Joong Sik Eom Tel +82-32-460-3741Fax +82-2-488-0119Email helppl@gachon.ac.krPurpose: To compare the clinical efficacy between peramivir and oseltamivir in hospitalized patients with influenza.Patients and Methods: Retrospective cohort study examined data from 542 adult patients with laboratory-confirmed seasonal influenza hospitalized in five teaching hospitals and one secondary hospital between August 2017 and May 2018. The main outcome was the defervescence rate within 3 days from the first administration of peramivir or oseltamivir. The secondary outcomes were mortality and duration of hospitalization/intensive care unit (ICU) stay.Results: Of the 542 enrolled patients, 251 were administered the standard dose of peramivir (300 mg, single dose), 42 were administered peramivir at doses exceeding 300 mg, and 249 were administered oseltamivir (75 mg, twice daily for 5 days). There were more ICU and pneumonia cases and older patients in the peramivir group, especially the high-dose group. The Charlson comorbidity index (CCI) scores were similar among the three groups. There were no significant differences in defervescence rates within 3 days between the three groups. The mortality and duration of hospital and ICU stays also did not differ significantly. The factors associated with 30-day mortality were ICU admission, high CCI score, and pneumonia.Conclusion: Treatment of influenza with either peramivir or oseltamivir in hospitalized adults resulted in generally similar clinical outcomes. Peramivir treatment showed good clinical response in influenza patients with pneumonia or admitted to the ICU.Keywords: influenza, human, therapeutics, oseltamivir, administration, intravenous

June Hong Ahn, Jin Hong Chung, Kyeong-Cheol Shin, Eun Young Choi, Hyun Jung Jin, Mi Suk Lee, Mi Jeong Nam, Kwan Ho Lee Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Yeungnam University, Daegu, South KoreaCorrespondence: Kwan Ho LeeDivision of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, South KoreaEmail ghlee@med.yu.ac.krObjective: Chronic obstructive pulmonary disease (COPD) acute exacerbations are significant causes of morbidity and mortality. “Frequent exacerbator” phenotypes are considered a distinct subgroup and this phenotype has a negative effect on lung function, quality of life, activity, hospital admission, and mortality. We assess inhaler handling technique and adherence, and evaluate risk factors associated with frequent exacerbations in COPD patients.Methods: This study was a cross-sectional, case-control study. We prospectively enrolled 189 COPD patients from Yeungnam University Hospital from January 2018 to November 2018. Subjects were tested regarding their inhaler technique in face-to-face interviews with an advanced practice nurse of inhaler upon study entry. Frequency of moderate to severe COPD exacerbations were reviewed via electronic medical records during 12 months prior to study entry. Frequent exacerbations were defined as ≥2 moderate to severe exacerbations in the prior 12 months. Multivariate logistic regression was performed to identify risk factors for frequent exacerbations.Results: Among 189 COPD patients, 50 (26.5%) were frequent exacerbators. Based on univariate analyses, body mass index (BMI) < 25 kg/m2, lower forced expiratory volume in 1 s (FEV1), higher mMRC, lower feeling of satisfaction with the inhaler, and any critical errors were potential risk factors for frequent exacerbations. Multivariate logistic regression analyses revealed that BMI < 25 kg/m2 (OR, 2.855, 95% CI, 1.247–6.534; p=0.013), higher mMRC (OR, 1.625, 95% CI, 1.072–2.463; p=0.022), and any critical error (OR, 2.020, 95% CI, 1.021–3.999; p=0.044) were risk factors.Conclusion: Any critical error, BMI < 25 kg/m2 and high mMRC are independent risk factors for frequent exacerbations in COPD patients. Careful monitoring and education around inhaler devices, particularly in frequent exacerbators, are important components of COPD treatment.Keywords: COPD, inhalation therapy, drug use error, disease exacerbation

Jong Geol Jang,1 Jee Seon Kim,2 Jin Hong Chung,1 Kyeong Cheol Shin,1 June Hong Ahn,1 Mi Sook Lee,3 So Hee Bang,3 Da Yeong Park,3 Mee Jung Nam,3 Hyun Jung Jin,1,* Kwan Ho Lee1,* 1Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Daegu, Republic of Korea; 2Department of Internal Medicine, Semyeong Christianity Hospital, Pohang, Republic of Korea; 3Department of Education and Management Services, Yeungnam University Medical Center,College of Medicine, Daegu, Republic of Korea*These authors contributed equally to this workCorrespondence: Hyun Jung JinDivision of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of KoreaTel +82-53-640-6578Fax +82-53-640-6449Email jhj0619@yu.ac.krBackground: Despite the increasing prevalence of chronic obstructive pulmonary disease (COPD) worldwide, knowledge and awareness of COPD remain extremely low. This prospective study aimed to demonstrate the effectiveness of organized educational intervention.Patients and methods: The study participants included patients diagnosed with COPD and receiving inhaler treatment. In this prospective study, the patients made three sequential visits to the hospital (baseline, 1 month, 3 months). On their first and second visits, patients received systematic education about COPD. On their first and third visits, each patient was evaluated using a COPD Assessment Test, COPD Knowledge Questionnaire, Hospital Anxiety and Depression Scale, and Rosenberg Self-Esteem Scale.Results: Fifty-five participants were enrolled in the study. The mean COPD knowledge score before and after education was 12.51±3.19 and 17.89±1.37, respectively, indicating a significant increase in the score post-education (P

Feng-Chih Kuo,1 Pao-Yen Lin,2 Jun-Wen Wang,1 Po-Chun Lin,1 Mel S Lee,1 Antonia F Chen3 1Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan; 2Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan; 3Department of Orthopaedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Purpose: Massive perioperative blood loss in complex revision total joint arthroplasty (TJA) often requires blood transfusions. Tranexamic acid (TXA) has been used in elective primary TJA to minimize blood loss and transfusions. The purpose of this meta-analysis was to evaluate the safety and efficacy of intravenous TXA in revision TJA. Methods: A literature search of PubMed, Scopus, and the Cochrane Controlled Trials Register was performed to identify studies published between January 2000 and May 2017. All randomized controlled trials (RCTs) and retrospective cohort observational studies evaluating the efficacy of intravenous TXA during revision total knee arthroplasty (TKA) and total hip arthroplasty (THA) were included. The mean differences (MDs) of blood loss, hemoglobin (Hb) change, and red blood cell (RBC) units transfused were compiled, and ORs of transfusion and venous thromboembolism (VTE) events in TXA and control groups were calculated. Results: Seven studies involving 930 patients were included (501 TXA vs 429 control). Intravenous TXA use had a significantly less blood transfusion (OR=0.20, 95% CI=0.11–0.34, P

Chanyoung Song,1,* Hathaichanok Phuengkham,1,* Sun-Young Kim,1 Min Sang Lee,2 Ji Hoon Jeong,2 Sung Jae Shin,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, 2Department of Pharmacy, Sungkyunkwan University, Suwon, 3Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: In this study, we suggest a designer vaccine adjuvant that can mimic the drainage of pathogens into lymph nodes and activate innate immune response in lymph nodes. By the amination of multivalent carboxyl groups in poly-(γ-glutamic acid) (γ-PGA) nanomicelles, the size was reduced for rapid entry into lymphatic vessels, and the immunologically inert nanomicelles were turned into potential activators of inflammasomes. Aminated γ-PGA nanomicelles (aPNMs) induced NLRP3 inflammasome activation and the subsequent release of proinflammatory IL-1β. The NLRP3-dependent inflammasome induction mechanism was confirmed through enzyme (cathepsin B and caspase-1) inhibitors and NLRP3 knockout mice model. After the aPNMs were combined with a clinically evaluated TLR3 agonist, polyinosinic–polycytidylic acid sodium salt (aPNM-IC), they triggered multiple arms of the innate immune response, including the secretion of pro-inflammatory cytokines by both inflammasomes and an inflammasome-independent pathway and the included type I interferons. Keywords: vaccine adjuvant, nanoparticles, innate immunity, antigen-presenting cells, lymphatic vessel, type I interferon

Ming-Song Lee,1,2 Chao-Ming Su,1 Jih-Chao Yeh,1,3 Pei-Ru Wu,4 Tien-Yao Tsai,1 Shyh-Liang Lou1,2 1Department of Biomedical Engineering, 2Department of Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan; 3Institute of Urology, University of Southern California, Los Angeles, CA, USA; 4Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan Abstract: Osteoporosis is a result of imbalance between bone formation by osteoblasts and resorption by osteoclasts (OCs). In the present study, we investigated the potential of limiting the aggravation of osteoporosis by reducing the activity of OCs through thermolysis. The proposed method is to synthesize bisphosphonate (Bis)-conjugated iron (II, III) oxide (Fe3O4) nanoparticles and incorporate them into OCs. The cells should be subsequently exposed to radiofrequency (RF) to induce thermolysis. In this study, particles of Fe3O4 were first synthesized by chemical co-precipitation and then coated with dextran (Dex). The Dex/Fe3O4 particles were then conjugated with Bis to form Bis/Dex/Fe3O4. Transmission electron microscopy revealed that the average diameter of the Bis/Dex/Fe3O4 particles was ~20 nm. All three kinds of nanoparticles were found to have cubic inverse spinel structure of Fe3O4 by the X-ray diffraction analysis. Fourier transform infrared spectroscopy confirmed that the Dex/Fe3O4 and Bis/Dex/Fe3O4 nanoparticles possessed their respective Dex and Bis functional groups, while a superconducting quantum interference device magnetometer measured the magnetic moment to be 24.5 emu. In addition, the Bis/Dex/Fe3O4 nanoparticles were fully dispersed in double-distilled water. Osteoblasts and OCs were individually cultured with the nanoparticles, and an MTT assay revealed that they were non-cytotoxic. An RF system (42 kHz and 450 A) was used to raise the temperature of the nanoparticles for 20 minutes, and the thermal effect was found to be sufficient to destroy OCs. Furthermore, in vivo studies verified that nanoparticles were indeed magnetic resonance imaging contrast agents and that they accumulated after being injected into the body of rats. In conclusion, we developed a water-dispersible magnetic nanoparticle that had RF-induced thermogenic properties, and the results indicated that the Bis/Dex/Fe3O4 nanoparticle had the potential for controlling osteoporosis. Keywords: iron oxide, thermotherapy, bisphosphonate, radiofrequency, thermolysis

Ling Bei,1 Iris Lee,2 Michael S Lee,3 Greg P Van Stavern,1 Collin M McClelland3 1Department of Ophthalmology and Visual Neurosciences, Washington University School of Medicine, St Louis, MO, 2Casey Eye Institute, Oregon Health and Science University, Portland, OR, 3Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA Abstract: Giant-cell arteritis (GCA) is a visually devastating disease that often progresses to severe bilateral vision loss if untreated. Diagnosis of GCA is made challenging by the protean nature of the disease and the lack of a simple test that is both highly sensitive and specific. Choroidal filling delay on fluorescein angiography (FA) has been touted as a highly characteristic feature of GCA-related vision loss, although knowledge of both the sensitivity and specificity of this finding remains unproven. We report our experience of delayed choroidal filling on FA in a series of seven patients referred to an academic neuro-ophthalmology practice due to concern for GCA. Despite the FA findings, our examination, diagnostic testing, and long-term follow-up excluded the diagnosis of GCA in all cases, suggesting that choroidal perfusion abnormalities may occur in the absence of GCA. When evaluating a patient for acute vision loss, the astute clinician must remain cognizant of the limitations of FA in the diagnosis of GCA.Keywords: giant-cell arteritis, fluorescein angiography, delayed choroidal filling

Nai-Huan Hsiung,1 Yen Yang,1 Ming Shinn Lee,2 Koustuv Dalal,3 Graeme D Smith4 1Department of Nursing, College of Nursing, Tzu Chi University of Science and Technology, 2Department of Curriculum Design and Human Potentials Development, National Dong Hwa University, Hualien, Taiwan, Republic of China; 3Department of Public Health Science, School of Health Sciences, Örebro University, Örebro, Sweden; 4School of Nursing, Midwifery & Social Care, Edinburgh Napier University, Edinburgh, UK Abstract: This study describes the cultural adaptation and testing of the behavioral pain scale (BPS) and the critical-care pain observation tools (CPOT) for pain assessment in Taiwan. The cross-cultural adaptation followed the steps of translation, including forward translation, back-translation, evaluation of the translations by a committee of experts, adjustments, and then piloting of the prefinal versions of the BPS and the CPOT. A content validity index was used to assess content validities of the BPS and the CPOT, with 0.80 preset as the level that would be regarded as acceptable. The principal investigator then made adjustments when the content validity index was

Wei-Hsiu Hsu,1–3 Chi-lung Chen,2 Liang Tseng Kuo,2 Chun-Hao Fan,1 Mel S Lee,2 Robert Wen-Wei Hsu2 1Sports Medicine Center, Chang Gung Memorial Hospital at Chia Yi, Chia Yi, Taiwan; 2Division of Sports Medicine, Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Chia Yi, Chia Yi, Taiwan; 3Department of Medicine, Chang Gung University, Tao Yuan, Taiwan Background: Health-related fitness has been reported to be associated with improved quality of life (QoL) in the elderly. Health-related fitness is comprised of several dimensions that could be enhanced by specific training regimens. It has remained unclear how various dimensions of health-related fitness interact with QoL in postmenopausal women.Objective: The purpose of the current study was to investigate the relationship between the dimensions of health-related fitness and QoL in elderly women.Methods: A cohort of 408 postmenopausal women in a rural area of Taiwan was prospectively collected. Dimensions of health-related fitness, consisting of muscular strength, balance, cardiorespiratory endurance, flexibility, muscle endurance, and agility, were assessed. QoL was determined using the Short Form Health Survey (SF-36). Differences between age groups (stratified by decades) were calculated using a one-way analysis of variance (ANOVA) and multiple comparisons using a Scheffé test. A Spearman’s correlation analysis was performed to examine differences between QoL and each dimension of fitness. Multiple linear regression with forced-entry procedure was performed to evaluate the effects of health-related fitness. A P-value of

Adyani Md Redzuan, Meng Soon Lee, Noraida Mohamed Shah Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Purpose: Asthma affects an estimated 300 million people worldwide. Poor adherence to prescribed preventive medications, especially among children with asthma, leads to increased mortality and morbidity. The purpose of this study was to assess the adherence and persistence levels of asthmatic children at the Universiti Kebangsaan Malaysia Medical Center (UKMMC), a tertiary care teaching hospital, and to determine the factors that influence adherence to prescribed preventive medications. Patients and methods: Participants were asthmatic patients aged 18 years and younger with at least one prescription for a preventive medication refilled between January and December 2011. Refill records from the pharmacy dispensing database were used to determine the medication possession ratio (MPR) and continuous measure of gaps (CMG), measures of adherence and persistence levels, respectively. Results: The sample consisted of 218 children with asthma from the General and Respiratory pediatric clinics at UKMMC. The overall adherence level was 38% (n=83; MPR ≥80%), and the persistence level was 27.5% (n=60; CMG ≤20%). We found a significant association between the adherence and persistence levels (r=0.483, P0.05). Conclusion: In conclusion, the adherence level among children with asthma at UKMMC was low. The presence of comorbidities was found to influence adherence towards preventive medications in asthmatic children. Keywords: asthma, persistence, non adherence, pediatric patients, medication possession ratio

Joo-Yeon Kim,1,* Mak-Soon Lee,1,* Sunyoon Jung,1 Hyunjin Joo,1 Chong-Tai Kim,2 In-Hwan Kim,3 Sangjin Seo,1 Soojung Oh,1 Yangha Kim11Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea; 2Functional Materials Research Group, Korea Food Research Institute, Seongnam, Gyeonggi, Republic of Korea; 3Department of Food and Nutrition, Korea University, Seoul, Republic of Korea *These authors contributed equally to this workPurpose: This study determined the effects of oleoresin capsicum (OC) and nanoemulsion OC (NOC) on obesity in obese rats fed a high-fat diet.Methods: The rats were randomly separated into three groups: a high-fat (HF) diet group, HF + OC diet group, and HF + NOC diet group. All groups were fed the diet and water ad libitum for 14 weeks.Results: NOC reduced the body weight and adipose tissue mass, whereas OC did not. OC and NOC reduced mRNA levels of adipogenic genes, including peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1c, and fatty acid-binding protein in white adipose tissue. The mRNA levels of genes related to β-oxidation or thermogenesis including PPAR-α, palmitoyltransferase-1α, and uncoupling protein-2 were increased by the OC and NOC relative to the HF group. Both OC and NOC clearly stimulated AMP-activated protein kinase (AMPK) activity. In particular, PPAR-α, palmitoyltransferase-1α, uncoupling protein-2 expression, and AMPK activity were significantly increased in the NOC group compared to in the OC group. NOC decreased glycerol-3-phosphate dehydrogenase activity whereas OC did not.Conclusion: From these results, NOC could be suggested as a potential anti-obesity agent in obese rats fed a HF diet. The effects of the NOC on obesity were associated with changes of multiple gene expression, activation of AMPK, and inhibition of glycerol-3-phosphate dehydrogenase in white adipose tissue.Keywords: oleoresin capsicum, nanoemulsion, anti-obesity, gene expression, AMP-activated protein kinase, rats

Accurate measurement of vital signs are important at skilled nursing facilities (SNF). Recent technological advancements now enable automated vital sign measurements. This overcomes the limitations of traditional manual vital sign measurement, which is time-consuming and error-prone. We present a novel case where continuous vital sign measurement was used to detect meaningful vital sign changes that led to early detection of a COVID-19 outbreak at a SNF. Residents were continuously monitored for changes to baseline respiratory rate and heart rate and with a Probability of Change (POC). Variations in baseline respiratory rate and heart rate occurred in 66% and 42%, respectively, of COVID-19 positive individuals; 83% of participants had statistically significant variations in either vital sign. Clinical investigations are typically triggered by vital signs outside normal ranges. We present a novel methodology to detect subtle vital sign changes that can lead to earlier diagnosis, treatment, and recovery from infections, like COVID-19.

Juwan Park1, Michael S Lee2, Andrew R Harrison31Department of Ophthalmology, The Catholic University of Korea, Seoul, Korea; 2Department of Ophthalmology, Neurology and Neurosurgery, 3Department of Ophthalmology and Otolaryngology, University of Minnesota, MN, USAAbstract: Even though conventional botulinum neurotoxin (BoNT) products have shown successful treatment results in patients with benign blepharospasm (BEB), the main, potential long-term side effect of BoNT use is the development of immunologic resistance due to the production of neutralizing antibody to the neurotoxin after repeated injections. Xeomin® (incobotulinumtoxinA), a unique botulinum neurotoxin type A (BoNT/A) drug free of complexing proteins otherwise contained in all conventional BoNT/A drugs, was recently approved by US Food and Drug Administration for the treatment of cervical dystonia or blepharospasm in adults. The newly approved BoNT/A drug may overcome this limitation of previous conventional products, since it contains pure neurotoxin (150 kDa) through a manufacturing process that separates it from complexing proteins such as hemagglutinins produced by fermentation of Clostridium botulinum. Many studies have also shown that Xeomin® has the same efficacy and safety profile as complexing protein-containing products such as Botox® and is exchangeable with Botox® using a simple 1:1 conversion ratio. Xeomin® represents a new treatment option for the repeated treatment of patients with blepharospasm in that it may reduce antibody-induced therapy failure. But, long-term comparative trials in naïve patients between Xeomin® and conventional BoNT/A drugs are required to confirm the low immunogenicity of Xeomin®.Keywords: blepharospasm, botulinum neurotoxin type A, Xeomin®, incobotulinumtoxinA, complexing proteins, neutralizing antibodies

The ability to systematically modify the magnetic properties of epitaxial La0.7Sr0.3MnO3 thin films is demonstrated through the use of Ar+ ion implantation. With increasing implant dose, a uniaxial expansion of the c-axis of the unit cell leads to a transition from in-plane toward perpendicular magnetic anisotropy. Above a critical dose of 3 × 1013 Ar+/cm2, significant crystalline disorder exists leading to a decrease in the average Mn valence state and near complete suppression of magnetization. Combined with lithographic techniques, ion implantation enables the fabrication of magnetic spin textures consisting of adjacent regions with tunable magnetic anisotropy in complex oxide thin films.

Complex oxide heterostructures provide access to emergent functional and structural phases which are not present in the bulk constituent materials. In this Rapid Communication, we focus on La0.67Sr0.33CoO3 (LSCO)/Gd heterostructures due to the high oxygen ion conductivity, as well as the coupled magnetic and electronic properties of LSCO, which are strongly dependent on the oxygen stoichiometry. This combination of properties enables the ionic control of the functional properties of LSCO thin films through the presence of oxygen getter layers such as Gd. We utilize X-ray nanodiffraction to directly image the nanoscale morphology of LSCO thin films as they are progressively transformed from the equilibrium perovskite phase to the metastable brownmillerite (BM) phase with increasing Gd thickness. Our studies show the coexistence of perovskite and BM phases with a critical oxygen vacancy concentration threshold which leads to the formation of extended BM filaments. In addition to lateral phase separation, we observed phase separation within the film thickness possibly due to pinning of the perovskite and BM phases by the substrate/LSCO and LSCO/Gd interface, respectively. Our studies provide a nanoscale survey of the phase separation in the cobaltites and shed light on the formation of the metastable BM phase.

Control of materials through custom design of ionic distributions represents a powerful new approach to develop future technologies ranging from spintronic logic and memory devices to energy storage. Perovskites have shown particular promise for ionic devices due to their high ion mobility and sensitivity to chemical stoichiometry. In this work, we demonstrate a solid-state approach to control of ionic distributions in (La,Sr)CoO3 thin films. Depositing a Gd capping layer on the perovskite film, oxygen is controllably extracted from the structure, up to 0.5 O/u.c. throughout the entire 36-nm thickness. Commensurate with the oxygen extraction, the Co valence state and saturation magnetization show a smooth continuous variation. In contrast, magnetoresistance measurements show no change in the magnetic anisotropy and a rapid increase in the resistivity over the same range of oxygen stoichiometry. These results suggest significant phase separation, with metallic ferromagnetic regions and oxygen-deficient, insulating, nonferromagnetic regions, forming percolated networks. Indeed, x-ray diffraction identifies oxygen-vacancy ordering, including transformation to a brownmillerite crystal structure. The unexpected transformation to the brownmillerite phase at ambient temperature is further confirmed by high-resolution scanning transmission electron microscopy which shows significant structural - and correspondingly chemical - phase separation. This work demonstrates room-temperature ionic control of magnetism, electrical resistivity, and crystalline structure in a 36-nm-thick film, presenting opportunities for ionic devices that leverage multiple material functionalities.

We have used soft x-ray photoemission electron microscopy to image the magnetization of single-domain La0.7Sr0.3MnO3 nanoislands arranged in geometrically frustrated configurations such as square ice and kagome ice geometries. Upon thermal randomization, ensembles of nanoislands with strong interisland magnetic coupling relax towards low-energy configurations. Statistical analysis shows that the likelihood of ensembles falling into low-energy configurations depends strongly on the annealing temperature. Annealing to just below the Curie temperature of the ferromagnetic film (TC=338K) allows for a much greater probability of achieving low-energy configurations as compared to annealing above the Curie temperature. At this thermally active temperature of 325 K, the ensemble of ferromagnetic nanoislands explore their energy landscape over time and eventually transition to lower energy states as compared to the frozen-in configurations obtained upon cooling from above the Curie temperature. Thus, this materials system allows for a facile method to systematically study thermal evolution of artificial spin ice arrays of nanoislands at temperatures modestly above room temperature.

Soft x-ray photoemission electron microscopy with an in situ magnetic field has been used to study the relationship between ferromagnetic and antiferromagnetic spin alignment and the switching/reversal field of epitaxial micromagnetic structures. We investigated a model system consisting of a bilayer of ferromagnetic La0.7Sr0.3MnO3 and antiferromagnetic LaFeO3 where the spin axes in each layer can be driven from mutually perpendicular (spin-flop) to parallel alignment by varying the temperature between 30 and 300 K. Results show that not only does this spin alignment noticeably influence the bilayer micromagnet coercivity compared to La0.7Sr0.3MnO3 single-layer micromagnets, but the coercivity within this materials system can be tuned over a wide range by careful balance of material properties.