Search

Joon Young Choi,1 Chin Kook Rhee2 1Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Chin Kook Rhee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea, Tel +82 2 2258 6067, Fax +82 2 599 3589, Email chinkook77@gmail.comAbstract: Asthma is a chronic inflammatory airway disease with significant burden; exacerbations can severely affect quality of life and healthcare costs. Advances in big data analysis and artificial intelligence have made it easier to predict future exacerbations more accurately. This study used an integrated dataset of Korean National Health Insurance, meteorological, air pollution, and viral data from national public databases to develop a model to predict asthma exacerbations on a daily basis in South Korea. We merged these sources and applied random forest, AdaBoost, XGBoost, and LightGBM machine learning models to compare their performances at predicting future exacerbations. Of the models, XGBoost (AUROC of 0.68 and accuracy of 0.96) and LightGBM (AUROC of 0.67 and accuracy of 0.96) were the most promising. Common important variables were the number of visits and exacerbations per year, and medical resource utilization, including the prescription of asthma medications. Comorbid diabetes, hypertension, gastroesophageal reflux, arthritis, metabolic syndrome, osteoporosis, and ischemic heart disease were also associated with elevated exacerbation risk. The models examined in this study highlight the importance of previous exacerbations, use of medical resources, and comorbidities in the prediction of future exacerbations in patients with asthma.Keywords: asthma, machine learning, big data analysis, South Korea, XGBoost, LightGBM

Yu Been Shin,1,&ast; Ju-Yeon Choi,2,&ast; Moon Sup Yoon,1 Myeong Kyun Yoo,1 Dae Hwan Shin,1,3,&ast; Jeong-Won Lee4,5,&ast; 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Chungbuk National University Hospital, Chungbuk National University, Cheongju, 28644, Republic of Korea; 4Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 5Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Dae Hwan Shin, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, 28160, Republic of Korea, Tel +82 43 261 2820, Fax +82 43 268 2732, Email dshin@chungbuk.ac.kr Jeong-Won Lee, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, South Korea, Zip 06351, Tel\Fax +82-2-3410-1382, Email garden.lee@samngsung.comPurpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer.Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system.Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was > 65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (&ast;&ast;p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo.Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer. Keywords: mixed micelle, combination therapy, nanoformulation, IV formula, antitumor efficacy

Ja Yun Choi,1 Eui Jeong Ryu2 1College of Nursing, Chonnam National University, Chonnam Research Institute of Nursing Science, Gwangju, Republic of Korea; 2Department of Nursing, Dongshin University, Naju, Republic of KoreaCorrespondence: Eui Jeong Ryu, Department of Nursing, Dongshin University, 34-22, Dongshin-daegil, Naju, Jeolla Province, 58245, Republic of Korea, Tel +82-10-9193-9075, Fax +82-61-225-3307, Email yeswecan9075@naver.comBackground: The relevant factors and patterns of non-adherence to self-management among patients with chronic obstructive pulmonary disease (COPD) need to be elucidated to improve self-management.Purpose: This study was a survey to prioritize the relevance of factors associated with non-adherence to COPD self-management using the Delphi technique and analytic hierarchy process (AHP).Patients and Methods: A total of 15 expert panels were established to determine the priority of relevant factors in a three-round Delphi survey and an AHP. To develop the preliminary conceptual framework for non-adherence to COPD self-management, findings from a systematic literature review, a qualitative study using in-depth interviews with COPD patients, and the first round of the Delphi survey were integrated. Based on the preliminary framework, the content validity ratio (CVR) was analyzed to examine the consensus among expert panels in the second and third rounds of the Delphi survey, and the relative weight was determined by pairwise comparisons between alternative factors in the AHP.Results: In developing the preliminary conceptual framework, 8 factor categories and 53 factors were identified as relevant to non-adherence to COPD self-management. Of the 53 factors, 22 factors with a CVR of 0.49 or higher were identified in the Delphi survey. A total of 14 of the 53 factors were common to both the Delphi survey and AHP with high weights. The most notable factors were prolonged treatment, experience of treatment failure, and unknown effects of medication.Conclusion: Through consensus decision-making by experts, 14 factors were identified as relevant factors associated with non-adherence to COPD self-management. A hierarchical and systematic framework incorporating factors associated with non-adherence to COPD self-management was developed in this study. Further research is needed to develop intervention strategies based on factors associated with non-adherence to COPD self-management.Keywords: chronic obstructive pulmonary disease, self-management, non-adherence, Delphi technique, analytic hierarchy process

Yoona Choi,1,2,&ast; Bo Kyung Kim,3,4,&ast; Jung-Hyun Won,2,5 Jae Won Yoo,6 Wona Choi,7 Surin Jung,7 Jae Yoon Kim,7,8 In Young Choi,7 Nack-Gyun Chung,6 Jae Wook Lee,6 Jung Yoon Choi,3,4 Hyoung Jin Kang,3,4,9 Howard Lee1,2,5,10,11 1Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; 2Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; 3Department of Pediatrics, Seoul National University Hospital, Seoul, Republic of Korea; 4Seoul National University Cancer Research Institute, Seoul, Republic of Korea; 5Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; 6Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 7Department of Medical Informatics, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 8Department of Biomedicine & Health Sciences, the Catholic University of Korea, Seoul, Republic of Korea; 9Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; 10Advanced Institutes of Convergence Technology, Suwon, Republic of Korea; 11Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Howard Lee, Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Email howardlee@snu.ac.kr Hyoung Jin Kang, Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Email kanghj@snu.ac.krBackground: Rapid reduction of leukemic cells in the bone marrow during remission induction chemotherapy (RIC) can lead to significant complications such as tumor lysis syndrome (TLS). We investigated whether prephase steroid treatment before RIC could decrease TLS incidence and improve overall survival in pediatric patients with acute lymphoblastic leukemia (ALL).Methods: Data were extracted from the Common Data Model databases in two tertiary-care hospitals in Seoul, South Korea. Patients were classified into the treated or untreated group if they had received RIC with prephase steroid treatment ≥ 7 days before RIC in 2012– 2021 or not, respectively. Stabilized Inverse Probability of Treatment Weighting (sIPTW) was applied to ensure compatibility between the treated and untreated groups. The incidence of TLS within 14 days of starting RIC, overall survival (OS), and the incidence of adverse events of special interest were the primary endpoints. Multiple sensitivity analyses were performed.Results: Baseline characteristics were effectively balanced between the treated (n=308.4) and untreated (n=246.6) groups after sIPTW. Prephase steroid treatment was associated with a significant 88% reduction in the risk of TLS (OR 0.12, 95% CI: 0.03– 0.41). OS was numerically greater in the treated group than in the untreated group although the difference was not statistically significant (HR 0.64, 95% CI 0.25– 1.64). The treated group experienced significantly elevated risks for hyperbilirubinemia and hyperglycemia. The reduction in TLS risk by prephase steroid treatment was maintained in all of the sensitivity analyses.Conclusion: Prephase steroid treatment for ≥ 7 days before RIC in pediatric patients with ALL reduces the risk of TLS, while careful monitoring for toxicities is necessary. If adequately analyzed, real-world data can provide crucial effectiveness and safety information for proper management of pediatric patients with ALL, for whom prospective randomized studies may be difficult to perform for ethical and practical reasons.Keywords: pediatric acute lymphoblastic leukemia, tumor lysis syndrome, remission induction chemotherapy, prephase steroid treatment, common data model

Yu Been Shin,1,&ast; Ju-Yeon Choi,2,&ast; Dae Hwan Shin,1 Jeong-Won Lee2,3 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea&ast;These authors contributed equally to this workCorrespondence: Dae Hwan Shin, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, 28160, Republic of Korea, Tel +82 43 261 2820, Fax +82 43 268 2732, Email dshin@chungbuk.ac.kr Jeong-Won Lee, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea, Tel +82-2-3410-1382, Fax +82-2-3410-0630, Email garden.lee@samsung.comPurpose: We aimed to inhibit ovarian cancer (OC) development by interfering with microtubule polymerization and inhibiting mTOR signaling. To achieve this, previously developed micelles containing fenbendazole and rapamycin were applied.Methods: Herein, we prepared micelles for drug delivery using fenbendazole and rapamycin at a 1:2 molar ratio and methoxy poly(ethylene glycol)-b-poly(caprolactone)(mPEG-b-PCL) via freeze-drying. We revealed their long-term storage capacity of up to 120 days. Furthermore, a cytotoxicity test was performed on the OC cell line HeyA8, and an orthotopic model was established for evaluating in vivo antitumor efficacy.Results: Fenbendazole/rapamycin-loaded mPEG-b-PCL micelle (M-FR) had an average particle size of 37.2 ± 1.10 nm, a zeta potential of − 0.07 ± 0.09 mV, and a polydispersity index of 0.20 ± 0.02. Additionally, the average encapsulation efficiency of fenbendazole was 75.7 ± 4.61% and that of rapamycin was 98.0 ± 1.97%. In the clonogenic assay, M-FR was 6.9 times more effective than that free fenbendazole/rapamycin. The in vitro drug release profile showed slower release in the combination formulation than in the single formulation.Conclusion: There was no toxicity, and tumor growth was suppressed substantially by our formulation compared with that seen with the control. The findings of our study lay a foundation for using fenbendazole and rapamycin for OC treatment.Keywords: ovarian cancer treatment, combination therapy, drug delivery, nanoformulation

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

Yoon Tae Goo,1,* Cheol-Ki Sa,1,* Ji Yeh Choi,2 Min Song Kim,1 Chang Hyun Kim,1 Hyeon Kyun Kim,1 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2Department of Psychology, York University, Toronto, Ontario, Canada*These authors contributed equally to this workCorrespondence: Young Wook ChoiCollege of Pharmacy, Chung-Ang University, 84 Heuksuk-Ro, Dongjak-Gu, Seoul, 06974, KoreaTel +82 2 820 5609Email ywchoi@cau.ac.krPurpose: To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed.Methods: Surfactants and solid carriers were screened based on a solubility and a flowability test, respectively. Supersaturating agents, including Poloxamer 407 (P407), were screened. The SSuM was optimized using a Box-Behnken design with three independent variables, including Gelucire 44/14:Brij L4 (G44/BL4; X1) and the amounts of Florite PS-10 (FLO; X2) and Vivapur 105 (VP105; X3), and three response variables, ie, dissolution efficiency at 30 min (Y1), dissolution enhancing capacity (Y2), and Carr’s index (Y3). The solid state property was evaluated, and a dissolution test was conducted. RVP, Revanex®, solid micelle (P407-free from the composition of SSuM), and SSuM were orally administrated to rats (RVP 20 mg equivalent/kg) for in vivo pharmacokinetic study.Results: G44 and BL4 showed great solubility, with a critical micelle concentration range of 119.2– 333.0 μg/mL. P407 had an excellent supersaturating effect. FLO and VP105 were selected as solid carriers, with a critical solidifying ratio (g/mL) of 0.30 and 0.91, respectively. With optimized values of X1 (– 0.41), X2 (0.31), and X3 (– 0.78), RVP (200 mg)-containing SSuM consisting of G44 (253.8 mg), BL4 (106.2 mg), FLO (99.3 mg), VP105 (199.8 mg), and P407 (40 mg) was developed, resulting in Y1 (40.3%), Y2 (0.008), and Y3 (12.3%). RVP existed in an amorphous state in the optimized SSuM, and the SSuM formed a nanosized dispersion in the aqueous phase, with approximately 71.7% dissolution at 2 h. The optimized SSuM improved the relative bioavailability of RVP in rats by approximately 478%, 276%, and 161% compared to raw RVP, Revanex®, and solid micelle, respectively.Conclusion: The optimized SSuM has great potential for the development of solidified formulations of poorly water-soluble drugs with improved oral absorption.Keywords: revaprazan, supersaturation, solid micelle, Box-Behnken design, dissolution, oral bioavailability

Joon Young Choi,1,* Shin Young Kim,2,* Jae Ha Lee,3 Yong Bum Park,4 Yee Hyung Kim,5 Soo-Jung Um,6 Ki Suck Jung,7 Kwang Ha Yoo,8 Seoung Ju Park,9 Hyoung Kyu Yoon10 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonology, Department of Internal Medicine, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea; 4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul 134-701, Republic of Korea; 5Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 6Division of Respiratory Medicine, Department of Internal Medicine, Dong-A University College of Medicine, Dong-A University Medical Center, Busan, Republic of Korea; 7Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Republic of Korea; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea*These authors contributed equally to this work.Correspondence: Hyoung Kyu YoonDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, #62 Youido-Dong Yeongdeungpo-Gu, Seoul, Republic of KoreaTel +82 2 3779 2213Fax +82 2 780 3132Email cmcyhg@gmail.comPurpose: The prevalence of chronic obstructive pulmonary disease (COPD) in females has increased, changing the concept of COPD as a disease mostly limited to males. In this study, the clinical characteristics of COPD in females were investigated.Patients and Methods: The study was based on a multicenter cohort of COPD patients recruited from 54 medical centers in South Korea. Sex-based differences in general characteristics, exposure risk factors, depression scores, results of pulmonary function tests, COPD exacerbation, symptom scores, and radiologic findings were evaluated. Sex-related differences in the annual FEV1 change over 5 years were analyzed in a linear mixed model.Results: Of the 2515 patients enrolled in this study, 8.1% were female. Female patients who had a higher BMI and a lower level of education were less likely to be smokers, were more exposed to passive smoking/biomass, and were more depressed compared to males. The rates of bronchiectasis, previous childhood respiratory infection, and asthma were higher in females. Female patients also had more symptoms and a poorer exercise capacity than males, but no significant differences were observed in terms of exacerbations. Radiologic findings revealed that male patients had worse emphysema, and female patients had worse bronchiectasis, as determined based on chest X-ray and computed tomography findings. On pulmonary function tests, female patients had less obstruction and less annual FEV1 loss over 5 years.Conclusion: This study revealed differences in the clinical parameters between male and female patients with COPD, including general characteristics, disease characteristics, and clinical outcomes.Keywords: COPD, gender difference, KOCOSS database, cohort study

Aim: Previous ovarian surgery for endometriosis results in decreased ovarian reserve and poor response to treatment in women with infertility. However, the impact of previous overall ovarian surgery on the incidence of infertility is unclear. Therefore the authors investigated impact of previous ovarian surgery on infertility incidence. Materials and Methods: This is a case-control study using retrospectively collected data in women who received infertility treatment (cases) or delivered babies (controls) at a tertiary center between 2003 and 2012. Results: The frequency of previous ovarian surgery was similar in both groups (p > 0.05) but it was higher in women with tubal infertility than their matched controls (p < 0.05). Also, the frequency of previous reproductive organ surgery was higher in the case group and in women with tubal or unexplained infertility (p < 0.05). Conclusion: Previous ovarian surgery is not associated with entire infertility, but may increase tubal factor infertility through adhesion formation and damage to adjacent tubes.

Joon Young Choi,1 Hyoung Kyu Yoon,2 Kyeong-Cheol Shin,3 So-Young Park,4 Chang Youl Lee,5 Seung Won Ra,6 Ki Suck Jung,7 Kwang Ha Yoo,4 Chang-Hoon Lee,8 Chin Kook Rhee9 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonology and Allergy, Regional Center for Respiratory Disease, Yeungnam University Medical Center, Daegu, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 7Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Chin Kook RheeDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul 06591, Republic of KoreaTel +82 2 2258 6067Fax +82 2 599 3589Email chinkook77@gmail.comPurpose: Previous studies have used various definitions to classify chronic obstructive pulmonary disease (COPD) patients into chronic bronchitis (CB) and non-CB patients. This study was performed to identify differences among three definitions of CB based on the classical method, St. George’s Respiratory Questionnaire (SGRQ), and the CAT (COPD Assessment Test) score.Patients and methods: We extracted data from the multicenter Korea COPD Subgroup Study (KOCOSS) cohort, for which patients recruited from among 47 medical centers in South Korea beginning in April 2012. Patients were classified according to three different definitions of CB: 1) classical definition; 2) SGRQ (using questions regarding cough and sputum); and 3) CAT score (comprising cough [CAT1] and sputum [CAT2] subscale scores).Results: A total of 2694 patients were enrolled in this study. The proportions of CB were 10.8%, 35.8%, and 24.0% according to the classical, SGRQ, and CAT definitions, respectively. The three definitions yielded consistently significant differences between CB and non-CB patients in modified Medical Research Council dyspnea scale CAT score, SGRQ score, number of moderate-to-severe exacerbations per year and forced expiratory volume in 1 second. By three definitions, CB consistently predicted future risk of exacerbation. The kappa coefficient of agreement between the classical definition and SGRQ definition was 0.29, that of the classical definition and CAT definition was 0.32, and that of the SGRQ definition and CAT definition was 0.44.Conclusion: Patients with CB according to the new definitions based on SGRQ or CAT score showed similar clinical characteristics to those defined according to the classical definition. The new CB definitions may be used as alternatives to the classical definition.Keywords: chronic bronchitis, CAT score, SGRQ score, chronic obstructive pulmonary disease, KOCOSS database

Jung-Yeon Choi,1 Sun-wook Kim,1 Sol-Ji Yoon,2 Min-gu Kang,1 Kwang-il Kim,1 Cheol-Ho Kim1 1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea; 2Department of Internal Medicine, Kangwon National University Hospital Gangwon-Do 200-722, Republic of Korea Purpose: Pneumonia poses a significant health risk in aging societies. We aimed to elucidate the determinative value of frailty for do-not-resuscitate (DNR) orders in pneumonia patients. Patients and methods: This was a retrospective cohort study conducted at the Seoul National University Bundang Hospital (SNUBH) in Korea. Medical records of 431 pneumonia patients, aged 65 years and older, who were admitted between June 2014 and May 2015 were analyzed. Patients were categorized into DNR and no-DNR groups. Results: Among the 65 patients (15.1% of pneumonia patients) who completed DNR documents, 24 patients were survived, and 21 patients decided imminent to death (

Jung Yeol Choi,1 Young Keun Han2,3 1Department of Ophthalmology, Jeju National University Hospital, Jeju, South Korea; 2Department of Ophthalmology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea; 3Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea Abstract: We describe a modified scleral fixation method to facilitate the good centration and adequate tension of sutures at both ends with addition of an internal fixation knot that reduces decentering of the IOL in a patient with postsurgical aphakia. Using an ab externo suture technique to fixate the haptics to the scleral wall, an additional loop knot is tied 1 mm next to the fixation knot at the haptic. In the technique, an internalized suture and an additional suture knot is tied while holding it close to the fixation knot at the haptic using a needle holder or McPherson forceps. The externalized sutures are secured by taking a bite of transclera and tying the suture to itself. This technique is simple and easy, and adds an internal check valve to prevent excessive pull and decentering of the intraocular lens at one side. The internal check valve also serves as a criterion for the point of fixation at each end. Keywords: modified technique, intraocular lens scleral fixation, postsurgical aphakia

Yun Jeong Lee,1 Hyewon Kim,1 Jiyeon Choi,1 Bo Hee Lee,1 Seok-Yong Lee2 1Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, Republic of Korea; 2Department of Pharmacy, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea Abstract: East Asians are prone to higher systemic exposure and increased risk of bleeding compared to other races after administration of antiplatelet agent(s). The aim of this systematic review was to compare and evaluate the appropriateness of a lower dose versus standard dose of ticagrelor in East Asians. A systematic search was conducted in PubMed, EMBASE, and Cochrane databases for studies comparing low versus standard doses of ticagrelor in East Asian populations; a total of seven studies were included in the review. Pharmacokinetic (PK), pharmacodynamic (PD), clinical efficacy, and safety data were collected. PK data demonstrated that the Cmax and area under the curve (AUC) of ticagrelor increased dose-proportionally. PD data indicated that while the low dose of ticagrelor resulted in less antiplatelet activity in three of the five PD studies, in the other studies, there were no differences between low and standard doses. There were two clinical studies included in this review, which showed that the efficacy was similar between the low and standard doses, but both studies were limited by the number of patients included. While there were generally greater incidence of adverse events observed in the standard ticagrelor dose, the magnitude or actual difference between the two doses is difficult to determine due to lack of consistent data. In East Asians, the appropriateness of the low-dose ticagrelor cannot be determined based on the currently available evidence. Additional large-scale and longer duration studies are warranted. Keywords: ticagrelor, P2Y12 receptor antagonist, lower dose, East Asians, Korean, Japanese, Chinese, efficacy, safety

Soon-Seok Hong,1 Ju Yeon Choi,2 Jong Oh Kim,2 Mi-Kyung Lee,3 So Hee Kim,4 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, 2College of Pharmacy, Yeungnam University, Gyeongsan, 3College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, 4College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, Republic of Korea Abstract: Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX) carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC)-based liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000)-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG]), produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol® while the toxicity of liposomal PTX was significantly lower than that of Taxol. Taken together, triglyceride incorporation provided an injectable PTX formulation by functioning as a formulation stabilizer of PEGylated/saturated PC-based liposomes. Keywords: paclitaxel, triglyceride, PEGylation, liposome, stability, formulation

Raj Kumar Thapa,1 Ju Yeon Choi,1 Bijay Kumar Poudel,1 Han-Gon Choi,2 Chul Soon Yong,1 Jong Oh Kim1 1College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongsanbuk-do, South Korea; 2College of Pharmacy, Hanyang University, Ansan, South Korea Abstract: Cancer is one of the leading causes of death worldwide. Although different chemotherapeutic agents have been developed to treat cancers, their use can be limited by low cellular uptake, drug resistance, and side effects. Hence, targeted drug delivery systems are continually being developed in order to improve the efficacy of chemotherapeutic agents. The main aim of this study was to prepare folic acid (FA)-conjugated polyvinyl pyrrolidone-functionalized graphene oxides (GO) (FA-GO) for targeted delivery of sorafenib (SF). GO were prepared using a modified Hummer’s method and subsequently altered to prepare FA-GO and SF-loaded FA-GO (FA-GO/SF). Characterization of GO derivatives was done using ultraviolet/visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, atomic force microscopy, zeta potential measurements, and determination of in vitro drug release. Hemolytic toxicity, in vitro cytotoxicity, cellular uptake, and apoptotic effects of FA-GO/SF were also investigated. The results revealed that GO was successfully synthesized and that further transformation to FA-GO improved the stability and SF drug-loading capacity. In addition, the enhanced SF release under acidic conditions suggested possible benefits for cancer treatment. Conjugation of FA within the FA-GO/SF delivery system enabled targeted delivery of SF to cancer cells expressing high levels of FA receptors, thus increasing the cellular uptake and apoptotic effects of SF. Furthermore, the photothermal effect achieved by exposure of GO to near-infrared irradiation enhanced the anticancer effects of FA-GO/SF. Taken together, FA-GO/SF is a potential carrier for targeted delivery of chemotherapeutic agents in cancer. Keywords: graphene oxide, folic acid, sorafenib, targeted drug delivery, near-infrared

Joon Young Choi,1 Hyoung Kyu Yoon,2 Seoung Ju Park,3 Yong Bum Park,4 Kyeong-Cheol Shin,5 Ju Ock Na,6 Kwang Ha Yoo,7 Ki-Suck Jung,8 Young Kyoon Kim,1 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, 4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, 5Regional Center for Respiratory Disease, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea Background: The chronic bronchitis (CB) phenotype has been associated with poor quality of life and an increased risk of disease in patients with COPD. However, little information exists regarding the relationship between the CB phenotype and the COPD assessment test (CAT) score. The goal of this study was to reveal the different pattern of CAT scores between CB and non-CB patients. Moreover, we aimed to investigate whether the CB phenotype is an independently associated factor for more symptom and high-risk groups.Methods: Data were obtained from the Korea COPD Subgroup Study cohort recruited from 46 centers in South Korea since April 2012. CB patients were defined as having a chronic cough and sputum for 3 months per year, for a period of 2 consecutive years. We investigated the pattern of CAT and subquestionnaire scores between CB and non-CB patients. We also analyzed the proportion of CB phenotypes in each Global initiative for chronic Obstructive Lung Disease (GOLD) stage. Finally, we performed a logistic regression analysis to identify whether the CB phenotype was an independently associated factor for more symptom and high-risk groups.Results: Of the 1,106 study patients, 11.5% of patients were found to have a CB phenotype. CB phenotypes were most common in GOLD III (GOLD 2006) and GOLD D (GOLD 2015) stages. CAT scores were significantly higher in CB patients not only in terms of the total score but also for each subquestionnaire. Logistic regression revealed that the CB phenotype is an independently associated factor for more symptom and high-risk groups.Conclusion: The present study revealed that CB patients have higher CAT scores and subquestionnaire results compared to non-CB patients. Additionally, we demonstrated that the CB phenotype is an independently associated factor for both more symptom and high-risk groups. Keywords: chronic obstructive pulmonary disease, chronic bronchitis, COPD assess­ment test

Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan, South KoreaAbstract: The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.Keywords: docetaxel, polyaspartic acid, drug delivery systems, antitumor, pH-sensitive

Dong Wuk Kim,1,* Thiruganesh Ramasamy,2,* Ju Yeon Choi,2 Jeong Hwan Kim,2 Chul Soon Yong,2 Jong Oh Kim,2 Han-Gon Choi1 1College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea; 2College of Pharmacy, Yeungnam University, Gyongsan, South Korea *These two authors contributed equally to this work Abstract: The primary aim of this work was to investigate the potential of bile salt, sodium taurocholate (NaTC), in improving the bioavailability and anti-tumor efficacy of docetaxel (DCT) upon rectal administration. Poloxamer-based nanomicelles with thermosensitive and mucoadhesive properties were prepared using the cold method. The optimized nanomicellar formulation was evaluated in terms of physicochemical and viscoelastic parameters. Nanomicelles containing bile salt maintained sufficient gelation strength (234×102 mPa·s) and mucoadhesive force (17.3×102 dyne/cm2) to be retained in the upper part of the rectum. They significantly enhanced the DCT internalization across the rectal mucosa and showed a high plasma level during the first 4 hours of the study period, compared to nanomicelles with no bile salt. As a result, a slightly higher rectal bioavailability of ~33% was observed in nanomicelles containing bile salt, compared to ~28% from the latter system. The higher pharmacokinetic parameters for rectally administered DCT/P407/P188/Tween 80/NaTC (0.25%/11%/15%/10%/0.1% by weight, respectively) resulted in significant anti-tumor efficacy. However, the tumor regression rate for the NaTC group was not statistically different from that for nanomicelles without NaTC. Therefore, overall results suggest that thermosensitive nanomicelles could be a potential dosage form for improvement of the bioavailability and chemotherapeutic profile of DCT. Keywords: anti-cancer efficiency, bioavailability, docetaxel, liquid suppository, rectal delivery, thermosensitive

BackgroundIdentifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients.AimTo investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy.MethodsEnvironmental swab samples and air samples were collected from the isolation rooms of three COVID-19 patients with severe pneumonia. Patients 1 and 2 received mechanical ventilation with a closed suction system, while patient 3 received high-flow oxygen therapy and non-invasive ventilation. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT-PCR.FindingsOf the 48 swab samples collected in the rooms of patients 1 and 2, only samples from the outside surfaces of the endotracheal tubes tested positive for SARS-CoV-2 by rRT-PCR. However, in patient 3's room, 13 of the 28 environmental samples (fomites, fixed structures, and ventilation exit on the ceiling) showed positive results. Air samples were negative for SARS-CoV-2. Viable viruses were identified on the surface of the endotracheal tube of patient 1 and seven sites in patient 3's room.ConclusionEnvironmental contamination of SARS-CoV-2 may be a route of viral transmission. However, it might be minimized when patients receive mechanical ventilation with a closed suction system. These findings can provide evidence for guidelines for the safe use of personal protective equipment.

With increasing global uptake of variable-speed (inverter-driven) air conditioners (ACs), the globally uniform energy-efficiency ratio (EER) metric has given way to various region-specific part-load and seasonal performance AC metrics in many markets. As a result, policymakers around the world lack comparative data that might help them create more effective AC efficiency market-transformation programs. To help fill this gap, this paper explores relationships between the room AC efficiency performance metrics of different regions—including China, the European Union, India, Japan, South Korea, and the United States—using performance data for split room AC models. We use these interregional conversion relationships to estimate the performance of >6000 AC models, including reversible heat pumps, in efficiency metrics used in the six economies as well as the International Organization for Standardization (ISO) 16,358 metric. Our results suggest a way to identify the potential for improving AC efficiency policies in regional markets. The most efficient models sold in each region and worldwide typically are more efficient than the most efficient level recognized by regional energy standards and labeling programs. This information could help policymakers evaluate and improve their AC efficiency market-transformation programs to align with the globally best-available technology.

© 2015 IEEE. A novel algorithm and implementation of real-time identification and tracking of blob-filaments in fusion reactor data is presented. Similar spatio-temporal features are important in many other applications, for example, ignition kernels in combustion and tumor cells in a medical image. This work presents an approach for extracting these features by dividing the overall task into three steps: local identification of feature cells, grouping feature cells into extended feature, and tracking movement of feature through overlapping in space. Through our extensive work in parallelization, we demonstrate that this approach can effectively make use of a large number of compute nodes to detect and track blob-filaments in real time in fusion plasma. On a set of 30 GB fusion simulation data, we observed linear speedup on 1,024 processes and completed blob detection in less than three milliseconds using Edison, a Cray XC30 system at NERSC.

ObjectivesHIV-associated neurocognitive disorder (HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine the prevalence of and risk factors for HAND in HIV-infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological (NP) tests for diagnosing HAND.MethodsHIV-infected patients were enrolled consecutively from two different urban teaching hospitals in Seoul, South Korea between March 2012 and September 2012. Participants completed a detailed NP assessment of six cognitive domains commonly affected by HIV. The Frascati criteria were used for diagnosing HAND. Four key questions, the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment (MoCA)-K were also assessed as potential tools for screening for HAND.ResultsAmong the 194 participants, the prevalence of HAND was 26.3%. Asymptomatic neurocognitive impairment and minor neurocognitive disorder accounted for 52.9 and 47.1% of the patients with HAND, respectively. In multivariate analysis, haemoglobin (Hb) level ≤ 13 g/dL (P = 0.046) and current use of a protease inhibitor-based regimen (P = 0.031) were independent risk factors for HAND. The sensitivity and specificity of the IHDS were 72.6 and 60.8%, and those of MoCA-K were 52.9 and 73.4%, respectively. The IHDS (P

: INTRODUCTION: Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART). METHODS: We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load RESULTS: Of 622 PWID from 12 countries in the Asia‐Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre‐ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year‐10 (n = 78). Higher follow‐up HIV viral load and pre‐ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2‐, 5‐ and 10‐years following ART initiation. There were 52 new AIDS‐defining events and 50 deaths during 3347 person‐years of follow‐up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings., INTRODUCTION Globally, injecting drug use is a major public health concern leading to substantial health burden and transmission risk of blood‐borne infections from injecting equipment sharing behaviours. In a multi‐stage [...]

UnlabelledBACKGROUND AND OBJECTIVE To examine the biophysical effects of photothermal heating on herniated intervertebral discs during laser decompression surgery.Study design/materials and methodsEx vivo bovine nucleus pulposus specimens were irradiated with a Nd: YAG laser (lambda = 1.32 microm, 100 seconds exposure time, 9-31 W/cm(2), 4.8 mm spot diameter), whereas changes in tissue thermal, mechanical, and optical properties were monitored by using, respectively, infrared radiometry, tissue tension measurements, and diffuse reflectance from a HeNe probe laser. Morphologic changes and mass reduction were monitored by recording shape changes on video and weighing specimens before and after laser exposure.ResultsAt power densities below 20 W/cm(2), evaporation of water and specimen volume reduction (shrinking) were consistently observed on video during irradiation. In contrast, above 20 W/cm(2), vapor bubbles formed within the specimen matrix and subsequently ruptured (releasing heated vapors). When radiometric surface temperature approaches approximately 60 to 70 degrees C (denaturation threshold for tissue), tissue tension begins to increase, which is consistent with observations of specimen length reduction. The onset of this change in tissue tension is also reflected in characteristic alterations in diffuse reflectance. With cessation of laser irradiation, a sustained increase in tissue tension is observed, which is consistent with changes in specimen length and volume. Higher laser power results in a faster heating rate and subsequently an accelerated tension change. Specimen mass reduction increased with irradiance from 19 to 72% of the initial mass for 9--31 W/cm(2), respectively. Irradiated specimens did not return to their original shape after immersion in saline (48 hours) in contrast to air-dried specimens (24 hours), which returned to their original shape and size.ConclusionThese observations suggest that photothermal heating results in irreversible matrix alteration causing shape change and volume reduction (observed on video and evidenced by the increase in tissue tension) taking place at approximately 65 degrees C. Inasmuch as high laser power results in vapor bubble formation and specimen tearing, the heating process must be controlled. Diffuse reflectance measurements provide a noncontact, highly sensitive means to monitor dynamically changes in tension of nucleus purposus.

: Introduction: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. Methods: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. Results: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person‐years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow‐up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co‐infection, TB diagnosis, HIV VL, CD4 count and BMI. Conclusions: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored., Introduction Cotrimoxazole (CTX) has been recommended as prophylaxis against Pneumocystis jiroveci pneumonia (PJP), toxoplasmosis, malaria and other serious bacterial infections in adults with severe or advanced HIV clinical disease, with [...]

Objectives: We conducted a longitudinal cohort analysis to evaluate the association of pre‐treatment body mass index (BMI) with CD4 recovery, virological failure (VF) and cardiovascular risk disease (CVD) markers among people living with HIV (PLHIV). Methods: Participants who were enrolled between January 2003 and March 2019 in a regional Asia HIV cohort with weight and height measurements prior to antiretroviral therapy (ART) initiation were included. Factors associated with mean CD4 increase were analysed using repeated‐measures linear regression. Time to first VF after 6 months on ART and time to first development of CVD risk markers were analysed using Cox regression models. Sensitivity analyses were done adjusting for Asian BMI thresholds. Results: Of 4993 PLHIV (66% male), 62% had pre‐treatment BMI in the normal range (18.5–25.0 kg/m2), while 26%, 10% and 2% were underweight (< 18.5 kg/m2), overweight (25–30 kg/m2) and obese (> 30 kg/m2), respectively. Both higher baseline and time‐updated BMI were associated with larger CD4 gains compared with normal BMI. After adjusting for Asian BMI thresholds, higher baseline BMIs of 23–27.5 and > 27.5 kg/m2 were associated with larger CD4 increases of 15.6 cells/µL [95% confidence interval (CI): 2.9–28.3] and 28.8 cells/µL (95% CI: 6.6–50.9), respectively, compared with normal BMI (18.5–23 kg/m2). PLHIV with BMIs of 25–30 and > 30 kg/m2 were 1.27 times (95% CI: 1.10–1.47) and 1.61 times (95% CI: 1.13–2.24) more likely to develop CVD risk factors. No relationship between pre‐treatment BMI and VF was observed. Conclusions: High pre‐treatment BMI was associated with better immune reconstitution and CVD risk factor development in an Asian PLHIV cohort. [ABSTRACT FROM AUTHOR]