Search

The concept and theory of potential vorticity in drift wave turbulence are extended to the case of an inhomogeneous magnetic field. A one-field magnetic potential vorticity conserving equation is derived via the use of conservative gyrokinetics. The similarity between the corresponding systems for drift wave turbulence and shallow water theory is discussed in detail. Zonal flow physics in an inhomogeneous magnetic field is discussed. In particular, a Charney–Drazin type nonacceleration theorem is derived from the novel system, which conserves magnetic potential vorticity. Extensions of the turbulent equipartition theory to the transport of magnetic potential vorticity are proposed.

Seho Kweon,1,2 Seong Jin Park,3 Ha Kyeong Lee,1 Seo Hee Kang,4 Kwan-Young Chang,4 Jeong Uk Choi,5 Jooho Park,6 Jung-Hyun Shim,7 Jin Woo Park,7 Youngro Byun1,3 1Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea; 2College of Pharmacy, Chonnam National University, Gwangju, 61186, Republic of Korea; 3College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; 4Global R&D Center, IcureBNP, Seoul, 06170, Republic of Korea; 5College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea; 6Department of Biomedical & Health Science, Konkuk University, Chungju, 27478, Republic of Korea; 7College of Pharmacy and Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, 58554, Republic of KoreaCorrespondence: Jin Woo Park; Youngro Byun, Tel +82 61 450 2704, Email jwpark@mokpo.ac.kr; yrbyun@snu.ac.krBackground: For maintenance therapy in type 2 diabetes, glucagon-like peptide-1 agonist (GLP-1A), which exhibits low cardiovascular risk and high efficacy, is a promising peptide therapeutic. However, developing an oral GLP-1A presents challenges due to the analog’s poor cellular permeability and gastrointestinal (GI) stability.Methods: To mitigate such limitations, an oral nanoformulation of liraglutide (LG) was designed and achieved by combining LG with bile acid derivatives using the nanoprecipitation method. This strategy allowed the bile acid moieties to localize at the nanoparticle surface, enhancing the binding affinity for apical sodium-dependent bile acid transporter (ASBT) and improving GI stability. The in vitro characteristics, cellular permeability, and absorption mechanisms of the LG nanoformulation (LG/TD-NF) were thoroughly investigated. Furthermore, the in vivo oral absorption in rats and the glucose-lowering effects in a diabetic (db/db) mouse model were evaluated.Results: The LG/TD-NF produced neutral nanoparticles with a diameter of 58.7 ± 4.3 nm and a zeta potential of 4.9 ± 0.4 mV. Notably, when exposed to simulated gastric fluid, 65.7 ± 3.6% of the LG/TD-NF remained stable over 120 min, while free LG was fully degraded. Relative to unformulated LG, the Caco-2 cellular permeability of the nanoformulation improved, measuring 10.9 ± 2.1 (× 10− 6 cm/s). The absorption mechanism prominently featured endocytosis simultaneously mediated by both ASBT and epidermal growth factor receptor (EGFR). The oral bioavailability of the LG/TD-NF was determined to be 3.62% at a dosage of 10 mg/kg, which is 45.3 times greater than that of free LG. In a diabetes model, LG/TD-NF at 10 mg/kg/day exhibited commendable glucose sensitivity and reduced HbA1c levels by 4.13% within 28 days, similar to that of subcutaneously administered LG at a dosage of 0.1 mg/kg/day.Conclusion: The oral LG/TD-NF promotes ASBT/EGFR-mediated transcytosis and assures cellular permeability within the GI tract. This method holds promise for the development of oral GLP-1A peptides as an alternative to injections, potentially enhancing patient adherence to maintenance therapy.Keywords: nanoformulation of GLP-1A, oral liraglutide, ASBT-mediated endocytosis, EGFR

Xu Jiang,1 Sungyeun Bae,1 Deok Yong Yoon,2 Shin Jung Park,3 Jaeseong Oh,1 Joo-Youn Cho,1,4 Kyung-Sang Yu1,4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA; 3Department of Pharmaceutical Research Laboratory, Chong Kun Dang Research Institute, Chong Kun Dang Pharmaceutical Corporation, Yongin, Republic of Korea; 4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaCorrespondence: Kyung-Sang Yu, Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101, Dae-hak ro, Jong-ro gu, Seoul, 03080, Republic of Korea, Tel/Fax +82-2072-1666, Email ksyu@snu.ac.krPurpose: Empagliflozin is a sodium-glucose cotransporter 2 inhibitor that is commonly used for the treatment of type 2 diabetes mellitus. As cocrystal formulation can improve the chemical properties of drugs, CKD-370 was newly developed as a cocrystal formulation of empagliflozin with solvate L-proline. This study aimed to compare the pharmacokinetics, safety, and tolerability of these two empagliflozin formulations in healthy Korean subjects.Methods: A randomized, open-label, two-sequence, two-period crossover study was conducted on healthy Korean participants. The subjects received a single oral 25 mg dose of either test (CKD-370) or reference treatment (Jardiance®) tablet at each period. Plasma empagliflozin concentrations were determined using liquid chromatography with tandem mass spectrometry. Pharmacokinetic (PK) parameters were analyzed using non-compartmental methods. The primary PK parameters included the maximum concentration (Cmax) and the area under the concentration-time curve from 0 to last (AUClast). The safety of both formulations was monitored and evaluated.Results: A total of 28 healthy Korean adult subjects were randomized, and 27 subjects were included in the PK analysis. The mean ± standard deviation values of the primary PK parameters, Cmax and AUClast after administration of the test treatment, were 442.02 ± 103.37 μg/L and 3131.08 ± 529.30 μg·h/L, respectively, and those after administration of the reference treatment were 436.29 ± 118.74 μg/L and 3006.88 ± 514.21 μg·h/L, respectively. The geometric mean ratio and its 90% confidence interval of test to reference treatment for Cmax and AUClast were 1.0221 (0.9527– 1.0967) and 1.0411 (1.0153– 1.0677), respectively, which were within the commonly accepted bioequivalence criteria of 0.80 to 1.25. Both treatments were well-tolerated.Conclusion: The two formulations of empagliflozin showed similar PK characteristics and were generally well tolerated in healthy subjects.Keywords: T2DM, cocrystal, L-proline, biosimilar, CKD-370

Sang-Jin Park,1,* Seung Ro Han,2,3,* Yun Hee Kang,2,3,* 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*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

Jun-Young Park,1 Ja-Shil Hyun,2 Jun-Goo Jee,3 Sung Jean Park,2 Dongwoo Khang1,4 1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, Republic of Korea; 2College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, 21936, Republic of Korea; 3Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, 41566, Republic of Korea; 4Department of Physiology, College of Medicine, Gachon University, Incheon, 21999, Republic of KoreaCorrespondence: Dongwoo KhangDepartment of Physiology, College of Medicine, Gachon University, Incheon, 21999, South KoreaTel +82-32-899-6515Email dkhang@gachon.ac.krSung Jean ParkCollege of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, 21936, Republic of KoreaTel +82-32-899-6113Email psjnmr@gachon.ac.krBackground: Understanding structural interactions between the active drug and conjugated nanoparticles is critical for optimizing intracellular drug transport and for increasing nano drug efficacy. In this regard, analyzing the conformational deformation of conjugated drugs surrounding nanoparticles is essential to understand the corresponding nanodrug efficacy.Purpose: The objective of this study is to present an optimal synthesis method for efficient drug delivery through a clear structural analysis of nanodrugs according to the type of conjugation.Methods and Results: In this study, the structural variation of methotrexate (MTX) surrounding carbon nanotubes, depending on the type of conjugation style, such as covalent and non-covalent (PEGylation) bonds, was investigated. Specifically, covalent bonds of MTX surrounding CNTs induced greater structural deformation compared to non-covalent bonds (ie, PEGylated CNT).Conclusion: Greater changes in the structural variations of MTX analyzed by nuclear magnetic resonance (NMR) significantly improved the anti-inflammatory drug efficacy of human fibroblast-like synovial cells (FLS) via stable drug release in the extracellular environment and burst drug release under intracellular conditions.Keywords: structural deformation, methotrexate, covalent conjugation, rheumatoid arthritis, carbon nanotube

Eun-Ji Choi,1,2 Soon Ji Park,1 Yeong-Min Yoo,1 Ji-Uk Yoon,1,2 Sang-Wook Shin,1,2 Gyeong-Jo Byeon1,2 1Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea; 2Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of KoreaCorrespondence: Gyeong-Jo ByeonDepartment of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Geumoro 20, Yangsan, Gyeongnam, 50612, Republic of KoreaTel +82-55-360-2129Fax +82-55-360-2149Email byeongj@pusan.ac.krBackground: Transforaminal epidural steroid injections (TF-ESIs) effectively deliver small amounts of drugs to inflamed sites via the ventral epidural space. However, there is a high risk of nerve damage as the needle narrowly approaches the spinal nerve. Therefore, we devised an oblique interlaminar (OIL) approach as an alternative method. We compared the efficacy of fluoroscopic-guided OIL-ESIs with that of TF-ESIs in the management of lower back and unilateral lumbosacral radicular pain.Materials and Methods: Sixty-six patients were randomized to receive a fluoroscopic-guided ESI either through the OIL (n = 33, group OIL) or TF (n = 33, group TF) approach. They were evaluated for effective pain relief using the visual analogue scale (VAS) and for functional improvement using the Oswestry Disability Index (ODI) and Roland Morris Disability Questionnaire (RMDQ). Other outcome measures were the presence of ventral and contralateral spread of contrast, patients’ satisfaction, and adverse events.Results: There were no significant differences between the groups in the VAS, ODI, and RMDQ scores during the 12-week period. The differences in the ODI and RMDQ scores before and after the treatment were higher in group TF than in group OIL. The contralateral spread of contrast was higher in group OIL than in group TF. There were no significant differences in the other outcomes between the groups.Conclusion: ESIs delivered through the OIL approach are equally effective in pain relief and functional improvement as those delivered via the TF approach in the management of low back and unilateral lumbosacral radicular pain.Keywords: epidural analgesia, fluoroscopy, low back pain, radicular pain, steroid injection

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

Eun Kyung Choi, Ji-il Kim, Sang-Jin Park Department of Anesthesiology and Pain Medicine, Yeungnam University College of Medicine, Daegu, Republic of KoreaCorrespondence: Sang-Jin ParkDepartment of Anesthesiology and Pain Medicine, Yeungnam University College of Medicine, Hyeonchung-ro, Nam-gu, Daegu, Republic of KoreaTel +82-53-620-3366Fax +82-53-626-5275Email apsj0718@naver.comPurpose: Ultrasound-guided thoracic paravertebral block (TPVB) is an established means for providing postoperative analgesia in thoracic surgery. However, there are conflicting results regarding the efficacy of post-thoracotomy pain management of ultrasound-guided TPVB when compared with that using traditional landmark approach. We therefore conducted a comparative study to evaluate the analgesic efficacy of TPVB when pressure measurement during needle advancement is combined with an ultrasound-guided approach.Patients and Methods: The patients scheduled for lobectomy through thoracotomy were randomly allocated to receive either the ultrasound-guided approach only group (U group) or the ultrasound-guided approach combined with pressure measurement group (UP group) (n = 36 per group). Before thoracic muscle closure, 0.375% ropivacaine (20 mL) was administered as a bolus, followed by a continuous infusion of 0.2% ropivacaine (0.1 mL/kg/hr) in both groups. Postoperative pain was assessed using the visual analogue scale (VAS) pain score while resting and coughing. Local anesthetics and pethidine usage and sensory block area were also evaluated.Results: The UP group showed significantly lower VAS scores, local anesthetics and pethidine usage, and a wider sensory block area than the U group.Conclusion: A combined technique with ultrasound guidance and pressure measurement provided a superior analgesic effect over that of an ultrasound-guided approach alone for the management of post-thoracotomy pain.Keywords: postoperative analgesia, pressure measurement, thoracic surgery, ultrasound-guided, visual analogue scale

Sung Jean Park College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, KoreaCorrespondence: Sung Jean ParkCollege of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaEmail psjnmr@gachon.ac.krAbstract: Nanoparticles (NPs) are highly potent tools for the diagnosis of diseases and specific delivery of therapeutic agents. Their development and application are scientifically and industrially important. The engineering of NPs and the modulation of their in vivo behavior have been extensively studied, and significant achievements have been made in the past decades. However, in vivo applications of NPs are often limited by several difficulties, including inflammatory responses and cellular toxicity, unexpected distribution and clearance from the body, and insufficient delivery to a specific target. These unfavorable phenomena may largely be related to the in vivo protein–NP interaction, termed “protein corona.” The layer of adsorbed proteins on the surface of NPs affects the biological behavior of NPs and changes their functionality, occasionally resulting in loss-of-function or gain-of-function. The formation of a protein corona is an intricate process involving complex kinetics and dynamics between the two interacting entities. Structural changes in corona proteins have been reported in many cases after their adsorption on the surfaces of NPs that strongly influence the functions of NPs. Thus, understanding of the conformational changes and unfolding process of proteins is very important to accelerate the biomedical applications of NPs. Here, we describe several protein corona characteristics and specifically focus on the conformational fluctuations in corona proteins induced by NPs.Keywords: nanoparticle, protein corona, structure, surface characteristic, conformational change

Purpose: To assess the magnitude of dosimetric reductions of a focal and ultra-focal high-dose-rate (HDR) prostate brachytherapy treatment strategy relative to standard whole gland (WG) treatment. Methods and Materials: HDR brachytherapy plans for five patients treated with WG HDR monotherapy were optimized to assess different treatment strategies. Plans were generated to treat the hemigland (HG), one-third gland (1/3G), and one-sixth gland (1/6G), as well as to assess treating the WG with a boost to one of those sub-volumes (WG+HG, WG+1/3G, WG+1/6G). Dosimetric parameters analyzed included Target D90%, V100%, V150%, Bladder (B), Rectal (R), Urethral (U) D0.1, 1 and 2cc, Urethral V75%, and the V50% to the contralateral HG. Two-tailed t tests were used for comparison of means, and p-values less than 0.05 were considered statistically significant. Results: Target objectives (D90>100% and V100>97%) were met in all cases. Significant organs at risk dose reductions were achieved for all approaches compared with WG plans. 1/6G vs WG plans resulted in the greatest reduction in dose with a mean bladder D2cc 24.7 vs 64.8%, rectal D2cc 32.8 vs 65.3%, urethral D1cc 52.1 vs 103.8%, and V75 14.5 vs 75% (p < 0.05 for all comparisons). Conclusion: Significant dose reductions to organs at risk can be achieved using HDR focal brachytherapy. The magnitude of the reductions achievable with treating progressively smaller sub-volumes suggests the potential to reduce morbidity, but the clinical impact on morbidity and tumor control remain to be investigated.

Purpose: High-dose-rate (HDR) prostate brachytherapy delivers a heterogeneous dose distribution throughout the prostate gland. There is however limited information regarding the spatial distribution of this dose heterogeneity. To this end, we analyzed the magnitude and location of intraprostatic dose heterogeneity in HDR prostate brachytherapy. Methods and Materials: Five consecutive prostate cancer patients treated with HDR were analyzed. Based on CT-simulation images, each prostate was divided into three sections (apex, base, and mid-gland). These were further subdivided into eight symmetrical sections to give a total of 24 sections. Dose-volume histograms were analyzed from V100-V200% for these 24 sections comparing the means of individual regions, left vs right, apex vs base vs mid-gland, lateral vs medial, and anterior vs posterior. A separate analysis on dose as a function of individual region volume was also performed. Results: Analyses comparing the 24 regions showed a maximum 62% difference (range, 21.9-83.9%) at V130% and 19.9% (1.9-20.8%) at V200%. Seven regions were significantly decreased and one significantly elevated from V130-V180% when compared with the mean. The means for lateral sections were 1.57-fold higher than medial sections from V110-V200% (. p < 0.0001). The dose at the base was significantly higher than the rest of the gland from V120-V200 (V150, 35.6±16.2% vs 20.9±13.1%, p < 0.0001). Conclusions: There is significant intra-prostatic dose heterogeneity in prostate HDR brachytherapy. This is most notable in the increased dose to base and lateral portions of the gland. Further studies are needed to determine the impact of heterogeneity on clinical outcomes.

Purpose: To determine the utility of ureteral stents in interstitial gynecological brachytherapy. Methods and Materials: We reviewed 289 patients with cervix cancer treated with high-dose-rate interstitial brachytherapy who did not have pretreatment hydronephrosis to determine the relative incidence of benign ureteral strictures after treatment. We also did comparative dosimetry analysis in five cases of high-dose-rate brachytherapy. Bilateral ureteral stents were placed during the procedure. Three dosimetry plans were created to determine the impact of modifying clinical target volume (CTV) and applying ureteral dose constraints. In Plan 1, the ureters were contoured and excluded from the CTV and 120% dose constraints were applied. In Plan 2, the ureters were contoured and excluded, but no dose constraints were applied to the ureter. In Plan 3, the CTV was created as if the location of the ureters was unknown and then ureteral dose was determined. Results: There were 11 ureteral strictures observed in 255 nonstented cases and 0 ureteral strictures in 34 stented cases. Plan 1 reduced the ureter dose (D0.1cc) by a median 22% (7.0-53.8%) compared with Plan 2 and by a median of 30.9% (12.3-65%). compared with Plan3. Conclusions: Placement of stents and ureteral dose constraints facilitates dosimetry and reduces the dose to ureters. Temporary ureteral stents prevent obstruction during interstitial gynecologic brachytherapy and allows the ureters to be addressed as an organ at risk.

Dasohm Kim1,2, Min Soo Park1,2, Byung Won Yoo2, Taegon Hong2, Shin Jung Park3, Choon Ok Kim2 1Department of Pharmaceutical Medicine and Regulatory Sciences, College of Medicine and Pharmacy, Yonsei University, Incheon, Korea; 2Department of Clinical Pharmacology and Clinical Trials Center, Severance Hospital, Yonsei University Health System, Seoul, Korea; 3Chong Kun Dang Research Institute, Chong Kun Dang Pharmaceutical Corporation, Seoul, KoreaCorrespondence: Choon Ok KimDepartment of Clinical Pharmacology and Clinical Trials Center, Severance Hospital, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaTel +82 22 228 0455Fax +82 22 227 7890Email delivery98@yuhs.acBackground: Esomeprazole is the most effective treatment for acid-related disorders and is widely used with enteric coating due to rapid degradation in the acidic environment. However, the enteric-coated formulation delays absorption and onset of action. To overcome this limitation, an immediate-release formulation containing esomeprazole 20 mg and sodium bicarbonate 800 mg (IR-ESO) was developed.Purpose: To evaluate the safety, pharmacokinetics (PK), and pharmacodynamics of IR-ESO compared to those of esomeprazole 20 mg (ESO).Methods: A randomized, open-label, multiple-dose, two-treatment, two-sequence crossover study was conducted in 40 healthy male subjects. Subjects received either IR-ESO or ESO for 7 days. After single and multiple dosing, blood samples were collected for PK analysis, and intragastric pH was assessed by 24-hr pH monitoring.Results: Plasma esomeprazole exposure of IR-ESO was similar to that of ESO after single and multiple dosing. Time to peak concentration of IR-ESO (0.50–0.75 hr) was shorter than that of ESO (1.25–1.50 hr). Percentage changes in 24-hr integrated gastric acidity from baseline for IR-ESO were similar to those for ESO. In addition, mean time to maintain gastric pH >4 for 24 hr was similar for both drugs (IR-ESO 55.5–69.9% vs ESO 56.8–70.2%). Evaluation of time to first reach pH 4 after dosing indicated that IR-ESO showed a faster onset than ESO. All subjects found the drug tolerable, and there were no significant differences in adverse events between two drugs.Conclusion: This study showed that IR-ESO produced a rapid, safe and sustained gastric acid suppression (ClinicalTrials.gov: NCT03211143).Keywords: sodium bicarbonate, immediate-release esomeprazole, esomeprazole, 24-hr pH monitoring

Ijeoma M Muo,1 Sandra D MacDonald,2 Ritu Madan,3 Sung-Jun Park,1 Ahmed M Gharib,4 Pedro E. Martinez,5 Mary F Walter,3 Shanna B Yang,6 Justin A Rodante,7 Amber B Courville,6 Peter J Walter,8 Hongyi Cai,8 Michael Glicksman,3 Gioia M Guerrieri,5 Rivka R Ben-Dor,9 Ronald Ouwerkerk,4 Stephanie Mao,1 Jay H Chung1 1Laboratory of Obesity and Aging Research NHLBI, National Institutes of Health, Bethesda, MD 20892, USA; 2NHLBI Pulmonary Branch, Laboratory of Chronic Airway Infections, National Institutes of Health, Bethesda, MD 20892, USA; 3Diabetes Endocrinology and Obesity Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA; 4Biomedical and Metabolic Imaging Branch NIDDK, National Institutes of Health, Bethesda, MD 20892, USA; 5Section on Behavioral Endocrinology, NIMH, National Institutes of Health, Bethesda, MD 20892, USA; 6Clinical Center Nutrition Department, National Institutes of Health, Bethesda, MD 20892, USA; 7Laboratory of Inflammation and Cardiometabolic Diseases, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA; 8Mass Spectrometry Clinical Core, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA; 9NIMH, National Institutes of Health, Bethesda, MD 20892, USA Purpose: Roflumilast (Daliresp, Daxas) is a FDA-approved phosphodiesterase 4 (PDE4) inhibitor for the treatment of moderate-to-severe chronic obstructive pulmonary disease. In mice and in limited human studies, this oral medication can cause weight loss and improve insulin sensitivity. We set out to determine the mechanism of its effect on insulin sensitivity. Patients and methods: Eight adults with overweight/obesity and prediabetes received roflumilast for 6 weeks. Before and after roflumilast, subjects underwent tests of insulin sensitivity, mixed meal test, body composition, markers of inflammation, and mitochondria function. Dietary intake and physical activity were also assessed. Our primary outcome was the change in peripheral insulin sensitivity, as assessed by the hyper-insulinemic euglycemic clamp. Results: This study was underpowered for the primary outcome. Pre- and post-roflumilast mean peripheral insulin sensitivity were 48.7 and 70.0 mg/g fat free mass/minute, respectively, (P-value=0.18), respectively. Among the mixed meal variables, roflumilast altered glucagon-like peptide 1 (GLP-1) hormone the most, although the average effect was not statistically significant (P=0.18). Roflumilast induced a trend toward significance in 1) decreased energy intake (from 11,095 KJ to 8,4555 KJ, P=0.07), 2) decreased fat mass (from 34.53 to 32.97 kg, P=0.06), 3) decreased total and LDL cholesterol (P=0.06 for both variables), and 4) increased plasma free fatty acids (from 0.40 to 0.50 mEq/L, P=0.09) The interval changes in adiposity and free fatty acid were significantly associated with the subject’s age (P-value range=

A homologous series of propylene carbonate (PC) analog solvents with increasing length of linear alkyl substitutes were synthesized and used as co-solvents with PC for graphite-based lithium-ion half cells. A graphite anode reaches a capacity of around 310 mAh/g in PC and its analog co-solvents, with 99.95 percent Coulombic efficiency, similar to the values obtained with ethylene carbonate-based electrolytes. Solvent interaction with the graphite anode and subsequent decomposition determines the graphite anode performance. Gaseous products from cyclic carbonates with short alkyl chains cause exfoliation of the graphite anode; solvents with longer alkyl chains are able to prevent graphite exfoliation when used as co-solvents with PC. The PC co-solvents compete for solvation of the Li ion with the PC solvent, delaying PC co-intercalation. Reduction products of PC on a graphite surface via a single-electron path form a stable Solid Electrolyte Interphase (SEI), which allows the reversible cycling of graphite. © 2013 The Electrochemical Society.

Yong Suk Jo,1 Sung Kyoung Kim,2 Seoung Ju Park,3 Soo-Jung Um,4 Yong-Bum Park,5 Ki Suck Jung,6 Deog Kyeom Kim,7 Kwang Ha Yoo8 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Division of Pulmonology, St Vincent’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; 4Department of Internal Medicine, Division of Pulmonology, Dong-A University Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 6Department of Internal Medicine, Division of Pulmonary Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 7Department of Internal Medicine, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 8Department of Internal Medicine, Division of Pulmonary and Allergy Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: FEV1 is the gold standard for assessment of COPD. We compared efficacy of FEV1, inspiratory capacity (IC), and IC to total lung capacity (TLC) ratio in the evaluation of COPD and their association with exacerbation.Methods: We analyzed the association of dyspnea severity, quality of life status, and lung function with lung function measurements and exacerbation risk in 982 patients enrolled in the Korea COPD Subgroup Registry and Subtype Research study. Exacerbation and longitudinal lung function change were evaluated in 3 years’ follow-up.Results: The FEV1, IC, and IC to TLC ratio showed comparable negative correlations with dyspnea severity and quality of life status, and positive correlation with exercise capacity. In patients with >2 events/year, annual rate of change in FEV1 and IC tended to decline more rapidly in those with FEV1 50% (-14.46±19.40 mL/year vs 12.29±9.24 mL/year, P=0.213; -4.75±17.28 mL/year vs -78.05±34.16 mL/year, P=0.056 for FEV1 and IC, respectively), without significance.Conclusion: Longitudinal changes in IC and FEV1 were not significantly associated with exacerbation risk. Keywords: COPD, exacerbation, FEV1, inspiratory capacity

Sang Jun Park,1,2 Kyung Bong Yoon,1,2 Dong Ah Shin,3 Kiwook Kim,1 Tae Lim Kim,1 Shin Hyung Kim1,2 1Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea Background: A caudal epidural steroid injection (CESI) is a commonly used method to improve symptoms of lumbosacral pain. We compared the achievement of successful epidurograms and patient-reported clinical outcomes following different needle-insertion depths during CESI.Methods: For the conventional method group, the needle was advanced into the sacral canal. For the alternative method group, the needle was positioned immediately after penetration of the sacrococcygeal ligament. Epidural filling patterns and vascular uptake during fluoroscopy were determined to verify successful epidural injection. Procedural pain scores were investigated immediately after the procedure. Pain scores and patient global impression of symptom change were evaluated at 1-month follow-up.Results: Assessments were completed by 127 patients (conventional method, n=64; alternative method, n=63). The incidence of intravascular injection was significantly lower in the alternative method group than in the conventional method group (3.2% vs 20.3%, P=0.005). Procedural pain during needle insertion was significantly lower in the alternative method group (3.7±1.3 vs 5.3±1.2, P

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea Purpose: Improvement in the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), and identification of biomarkers for phenotype recognition will encourage good patient care by providing optimal therapy. We investigated club cell secretory protein (CC-16), a protective and anti-inflammatory mediator, as a new candidate biomarker for diagnosing ACO.Patients and methods: We performed a multicenter cohort study. A total of 107 patients were divided into three groups – asthma, COPD, and ACO – according to the Spanish guidelines algorithm, and enrolled into the study. Serum CC-16 levels were measured using commercial ELISA kits.Results: Serum CC-16 levels were the lowest in patients with ACO. Low serum CC-16 levels were a significant marker for the ACO even after adjustment for age, sex, and smoking intensity. Serum CC-16 levels were positively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%–75% of FVC, FEV1/FVC, vital capacity, and diffusing capacity of the lung for carbon monoxide, and were negatively correlated with smoking amount (pack-years), bronchodilator response, fractional residual capacity, residual volume, and number of exacerbations per year. FEV1 and serum CC-16 levels were significantly lower in patients with frequent exacerbations.Conclusion: Serum CC-16 has the potential to be a biomarker for ACO diagnosis and also treat frequent exacerbations in patients with chronic inflammatory airway diseases. Keywords: asthma, COPD, ACO, exacerbation, club cell secretory protein-16, smoking

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea Purpose: Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE). However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology. The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD.Patients and methods: We performed a multicenter cross-sectional cohort study. We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD.Results: Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD. Although the FEV1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD. CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD. According to a multivariate logistic regression analysis, FEV1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD. IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Adnan Khan,4 Jinhyuk Na,4 Youngja H Park,4 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea; 4Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Republic of Korea Purpose: Asthma–COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach. We investigated the urinary levels of L-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition.Patients and methods: We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm. Urinary L-histidine levels were measured using liquid chromatography-mass spectrometry. High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups.Results: Urinary L-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly. High urinary L-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount. Among patients with airflow obstruction, the urinary L-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm−3; and frequent exacerbations (P < 0.05).Conclusion: Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used. Keywords: asthma, COPD, ACO, urinary L-histidine, metabolomics, inhaled corticosteroid

Seon Ju Kim, Sang Jun Park, Duck Mi Yoon, Kyung Bong Yoon, Shin Hyung Kim Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Pulsed radiofrequency (RF) targeting the adjacent dorsal root ganglion (DRG) is one treatment option for lumbosacral radicular pain. However, the analgesic efficacy of this procedure is not always guaranteed. The aim of this retrospective study was to identify the predictors of the analgesic efficacy of pulsed DRG RF treatment in patients with chronic lumbosacral radicular pain. Methods: Patients who underwent pulsed DRG RF treatment from 2006 to 2017 at our clinic were enrolled. Positive response was defined as a ≥50% reduction in pain score from baseline at day 30. Patient demographics, pain-related factors, and clinical factors were evaluated using logistic regression analysis to identify the predictors of a positive response to the treatment. Results: A total of 60 patients satisfied the study protocol requirements. Twenty-eight patients (46.7%) had a positive outcome. Multivariate logistic regression analysis revealed that the absence of comorbid musculoskeletal pain (OR=0.518, 95% CI=0.029–0.858, P=0.033) and positive response to previous epidural steroid injection (OR=3.269, 95% CI=1.046–10.215, P=0.042) were independent predictors of the analgesic efficacy of pulsed DRG RF treatment. Conclusion: Comorbid musculoskeletal pain and previous epidural injection response appear to affect the outcome of pulsed DRG RF treatment in patients with chronic lumbosacral radicular pain. Keywords: pulsed radiofrequency, dorsal root ganglion, lumbosacral radicular pain, predictors, efficacy

We describe critical processing issues in our development of single-atom devices for solid-state quantum information processing. Integration of single 31P atoms with control gates and single electron transistor (SET) readout structures is addressed in a silicon-based approach. Results on electrical activation of low-energy (15 keV) P implants in silicon show a strong dose effect on the electrical activation fractions. We identify dopant segregation to the SiO2/Si interface during rapid thermal annealing as a dopant loss mechanism and discuss means to minimize it. Silicon nanowire SET pairs with nanowire width of 10-20 nm are formed by electron-beam lithography in SOI. We present initial results from Coulomb blockade experiments and discuss issues of control gate integration for sub-40 nm gate pitches. © 2004 Elsevier B.V. All rights reserved.

Yu Kyong Kim,1 Anhye Kim,1,2 Shin Jung Park,3 Howard Lee1,4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Clinical Trial Center, Ajou University Medical Center, Suwon, 3Research Institute, Chong Kun Dang Pharmaceutical Corp, Yongin, 4Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea Abstract: To evaluate the pharmacokinetic (PK) and tolerability profiles of a new tablet formulation of tacrolimus and its interindividual variability (IIV) in the systemic exposure, and to compare them with those of the conventional capsule formulation, a randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in 47 healthy males. The capsule or tablet formulation of tacrolimus was orally administered, and serial blood samples were collected up to 96 hours after dosing. Whole-blood tacrolimus concentration was determined using liquid chromatography–tandem mass spectrometry. The maximum whole-blood tacrolimus concentration (Cmax) and the area under the whole-blood tacrolimus concentration–time curve from 0 hour to the last quantifiable concentration (AUClast) were compared between the two formulations. The similarity factor (f2) of the in vitro dissolution profiles was calculated. The geometric mean ratio (90% confidence interval) of tablet to capsule was 0.9680 (0.8873–1.0560) and 1.0322 (0.9359–1.1385) for Cmax and AUClast, respectively. The IIV of Cmax and AUClast of the tablet was smaller than the capsule. The f2 values were >50 in all media. Both formulations were well tolerated. Thus, the tablet formulation of tacrolimus has smaller IIV in the systemic exposure than capsule, while having comparable PK and tolerability profiles, which may render it as a better treatment option for organ transplant patients. Keywords: new formulation, incrementally modified drug, comparative pharmacokinetics, healthy volunteers, immunosuppressant

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

Tran Thanh Tung,1,2 Dusan Losic,1 Seung Jun Park,3 Jean-Francois Feller,2 TaeYoung Kim3 1School of Chemical Engineering, The University of Adelaide, North Terrace, Adelaide, SA, Australia; 2Smart Plastics Group, European University of Brittany (UEB), LIMATB-UBS, Lorient, France; 3Department of Bionanotechnology, Gachon University, Sujeong-gu, Seongnam-si, Gyeonggi-do South Korea Abstract: We report a high-performance chemiresistive sensor for detection of volatile organic compound (VOC) vapors based on core-shell hybridized nanostructures of Fe3O4 magnetic nanoparticles (MNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT)-conducting polymers. The MNPs were prepared using microwave-assisted synthesis in the presence of polymerized ionic liquids (PILs), which were used as a linker to couple the MNP and PEDOT. The resulting PEDOT–PIL-modified Fe3O4 hybrids were then explored as a sensing channel material for a chemiresistive sensor to detect VOC vapors. The PEDOT–PIL-modified Fe3O4 sensor exhibited a tunable response, with high sensitivity (down to a concentration of 1 ppm) and low noise level, to VOCs; these VOCs include acetone vapor, which is present in the exhaled breath of potential lung cancer patients. The present sensor, based on the hybrid nanostructured sensing materials, exhibited a 38.8% higher sensitivity and an 11% lower noise level than its PEDOT–PIL-only counterpart. This approach of embedding MNPs in conducting polymers could lead to the development of new electronic noses, which have significant potential for the use in the early diagnosis of lung cancer via the detection of VOC biomarkers. Keywords: hybrid nanomaterials, nanoparticle, conducting polymer, electronic nose, lung cancer detection

Hiroharu Kamioka,1 Kiichiro Tsutani,2 Minoru Yamada,3 Hyuntae Park,4 Hiroyasu Okuizumi,5 Koki Tsuruoka,6 Takuya Honda,7 Shinpei Okada,8 Sang-Jun Park,8 Jun Kitayuguchi,9 Takafumi Abe,9 Shuichi Handa,5 Takuya Oshio,10 Yoshiteru Mutoh111Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Kyoto University Graduate School Research, Kyoto, Japan; 4Department of Functioning Activation, National Center for Geriatrics and Gerontology, Aichi, Japan; 5Mimaki Onsen (Spa) Clinic, Tomi, Nagano, Japan; 6Graduate School of Social Services, Japan College of Social Work, Tokyo, Japan; 7Japanese Society for the Promotion of Science, Tokyo, Japan; 8Physical Education and Medicine Research Foundation, Tomi, Nagano, Japan; 9Physical Education and Medicine Research Center Unnan, Shimane, Japan; 10Social Welfare Service Corporation CARE-PORT MIMAKI, Tomi, Nagano, Japan; 11The Research Institute of Nippon Sport Science University, Tokyo, JapanObjective: The objective of this review was to summarize evidence for the effectiveness of music therapy (MT) and to assess the quality of systematic reviews (SRs) based on randomized controlled trials (RCTs).Study design: An SR of SRs based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included were those with at least one treatment group in which MT was applied. We searched the following databases from 1995 to October 1, 2012: MEDLINE via PubMed, CINAHL (Cumulative Index of Nursing and Allied Health Literature), Web of Science, Global Health Library, and Ichushi-Web. We also searched all Cochrane Database and Campbell Systematic Reviews up to October 1, 2012. Based on the International Classification of Diseases, 10th revision, we identified a disease targeted for each article.Results: Twenty-one studies met all inclusion criteria. This study included 16 Cochrane reviews. As a whole, the quality of the articles was very good. Eight studies were about "Mental and behavioural disorders (F00-99)"; there were two studies on "Diseases of the nervous system (G00-99)" and "Diseases of the respiratory system (J00-99)"; and there was one study each for "Endocrine, nutritional and metabolic diseases (E00-90)", "Diseases of the circulatory system (I00-99)", and "Pregnancy, childbirth and the puerperium (O60)". MT treatment improved the following: global and social functioning in schizophrenia and/or serious mental disorders, gait and related activities in Parkinson's disease, depressive symptoms, and sleep quality.Conclusion: This comprehensive summary of SRs demonstrated that MT treatment improved the following: global and social functioning in schizophrenia and/or serious mental disorders, gait and related activities in Parkinson's disease, depressive symptoms, and sleep quality. MT may have the potential for improving other diseases, but there is not enough evidence at present. Most importantly, no specific adverse effect or harmful phenomenon occurred in any of the studies, and MT was well tolerated by almost all patients.Keywords: ICD-10, schizophrenia, mental disorders, Parkinson's disease, depression, sleep

Sung Jean Park,1 Dongwoo Khang21College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, South Korea; 2School of Nano and Advanced Materials Science Engineering and Center for PRC and RIGET, Gyeongsang National University, Jinju, South KoreaAbstract: The conformational changes of plasma protein structures in response to carbon nanotubes are critical for determining the nanotoxicity and blood coagulation effects of carbon nanotubes. In this study, we identified that the functional intensity of carboxyl groups on carbon nanotubes, which correspond to the water dispersity or hydrophilicity of carbon nanotubes, can induce conformational changes in the fibrinogen domains. Also, elevation of carbon nanotube density can alter the secondary structures (ie, helices and beta sheets) of fibrinogen. Furthermore, fibrinogen that had been in contact with the nanoparticle material demonstrated a different pattern of heat denaturation compared with free fibrinogen as a result of a variation in hydrophilicity and concentration of carbon nanotubes. Considering the importance of interactions between carbon nanotubes and plasma proteins in the drug delivery system, this study elucidated the correlation between nanoscale physiochemical material properties of carbon nanotubes and associated structural changes in fibrinogen.Keywords: carbon nanotubes, fibrinogen, nanotoxicity, conformational change, denaturation

Youngkyung Ko, NamRyang Kim, Seojin Park, Jun-Beom ParkDepartment of Periodontics, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, KoreaBackground: Soft tissue augmentation is a widely used procedure in partially and fully edentulous patients to increase soft tissue volume. Polyurethanes have been used for scaffolds in a variety of implantable devices. Artelon® is a degradable polyurethane that has been manufactured as fibers, films, and porous scaffolds to be used for various purposes. In this review, the characteristics of Artelon are described, and its clinical applications in orthopedics, dermatology, cardiovascular medicine, and dentistry are also discussed.Methods: A Medline (PubMed) search was conducted, and articles published in English were included. Keywords, including “Artelon”, “polyurethanes”, “soft tissue augmentation”, “biocompatibility”, “resorption”, “mechanical stability”, and “complications” were used in different combinations. Titles and abstracts were screened, and full text article analyses were performed.Results: Most of the studies reported orthopedic, dermal, and myocardial applications. There were only a few reports related to dental and implant applications. Artelon has been successfully used for reinforcement of soft tissues, including the rotator cuff, Achilles, patellar, biceps, and quadriceps tendons in orthopedic surgery, and is used clinically for the treatment of osteoarthritis in the hand, wrist, and foot. One type of Artelon material, Artelon Cosmetic, has been used in the dental field to increase soft tissue volume, and stable results are achieved for up to 6 months. This material is reported to be easily handled when cut to the desired shape, with little additional time needed for manipulation during surgery, eliminates the need for connective tissue autografts, and thereby decreases patient morbidity and postoperative discomfort, with increased likelihood of a positive subjective outcome.Conclusion: Artelon may be applied in the dental field to increase soft tissue volume. Further studies of various applications in dentistry with long-term results are needed to confirm the safety and efficacy of this material before it can be used on a routine basis in dentistry.Keywords: Artelon® Cosmetic, dentistry, soft tissue augmentation, polyurethanes

Delta neutrophil index (DNI), which reflects the fraction of immature granulocytes, is used to detect infection and sepsis from noninfectious conditions, but few studies have evaluated in the early stage of acute poisoning. This retrospective observational study was performed on acute poisoning patients who visited to the emergency department (ED) and were consecutively admitted in intensive care units over 18-month period. The serial DNI, conventional inflammatory biomarkers, and culture results were obtained in the ED and after admission. The outcomes were the identification of sepsis, bacteremia, and 30-day mortality. Of 166 patients (mean age, 56.0 years) in this cohort, 59 (35.5%) had sepsis and 29 (17.5%) had bacteremia. Initial and peak DNI fractions 24 h after ED admission were strong independent predictors of sepsis development. Analysis of the area under the curve according to multiple receiver operating characteristics showed that DNI had a higher capability to predict sepsis than other parameters (0.815 for DNI, 0.700 for procalcitonin, 0.681 for C-reactive protein, and 0.741 for white blood cell). Using multivariable logistic regression analysis, it was found that DNI was an independent predictor of sepsis (95% confidence interval (CI) of odds: 1.03–1.18) and bacteremia (95% CI: 1.01–1.14). Therefore, initial and serial measurement of DNI may serve as useful risk predictor for development of sepsis or bacteremia in acute poisoning. [ABSTRACT FROM AUTHOR]

Modifying electrical activation conditions have been used to improve in vitro embryo production and development in pigs. However, there is insufficient information about correlations of porcine embryo development with oocyte pre- and post-activation conditions. The purpose of this study was to compare the developmental rates of porcine oocytes subjected to different mannitol exposure times, either pre- or post-electrical activation, and to elucidate the reason for the optimal mannitol exposure time. Mannitol exposure times around activation were adjusted as 0, 1, 2 or 3 min. Blastocyst development were checked on day 7. Exposure of oocytes to mannitol for 1 or 2 min before electrical activation produced significantly higher blastocyst rates than exposure for 0 or 3 min. There was no significant difference in blastocyst rates when activated oocytes were exposed to mannitol for 0, 1, 2 or 3 min after electrical activation. While exposure of oocytes to mannitol for 1 min pre- and 3 min post-activation showed significantly higher blastocyst development than 0 min pre- and 0 min post-activation. It also showed higher maintenance of normal oocyte morphology than exposure for 0 min pre- and 0 min post-activation. In conclusion, exposure of oocytes to mannitol for 1 min pre- and 3 min post-activation seems to be optimal for producing higher in vitro blastocyst development of porcine parthenogenetic embryos. The higher blastocyst development is correlated with higher maintenance of normal morphology in oocytes exposed to mannitol for 1 min pre- and 3 min post-activation. [ABSTRACT FROM AUTHOR]

BACKGROUND: We aimed to investigate the effect of gender difference on the accessibility to emergency care, hospital mortality and disability in acute stroke care. METHODS: This study was performed on a single-tiered basic emergency medical service with a comprehensive national health insurance. Demographic variables, risk factors, elapsed time intervals, performing diagnosis and treatment options, hospital mortality, and modified Rankin Scale of acute ischemic stroke during 2008 were collected. We modeled the multivariate regression analysis for gender differences on the accessibility, hospital mortality, and disability. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated adjusting for potential risk factors. RESULTS: The total number of patients was 6635. The time from symptom onset to emergency department (ED) arrival and to computed tomography or magnetic resonance imaging scan and from ED arrival to computed tomography or magnetic resonance imaging scan was significantly longer in women. No significant difference was found in either the time to intravenous thrombolysis or in the number of patients who received intravenous thrombolysis, anti-platelet therapy, anti-coagulation, or operation. The hospital mortality rate was higher in women (3.9%) than in men (2.9%) (P = .03). The increased disability was significantly higher in women (67.8%) than in men (65.1%) (P = .02). The hospital mortality and increased disability showed a non-significant difference between the 2 genders in the adjusted model (OR, 1.10; 95% CI, 0.74-1.64) and (OR, 1.11; 95% CI, 0.96-1.28), respectively. CONCLUSION: The adjusted model for risk factors showed no significant difference on hospital mortality and disability between the 2 genders for stroke patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics.Methods: Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis.Results: TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV(1) and FVC (P < 0.05).Conclusions: Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT.Key Points: • In asthmatics, xenon ventilation decreases after methacholine and increases after salbutamol inhalation. • Inner airway area (IA) correlates well with xenon ventilation. • IA is the most reliable parameter reflecting airway changes in drug responses. [ABSTRACT FROM AUTHOR]

Background and Purpose: We previously reported that 3-(benzo[d]-1,3-dioxol-5-yl)-4-phenylfuran-2,5-dione (BPD) showed strong inhibitory effects on PGE(2) production. However, the exact mechanism for the anti-inflammatory effect of BPD is not completely understood. In this study, we investigated the molecular mechanism involved in the effects of BPD on inflammatory mediators in LPS-stimulated macrophages and animal models of inflammation.Experimental Approach: The expressions of COX-2, inducible NOS (iNOS), TNF-α, IL-6 and IL-1β, in LPS-stimulated RAW 264.7 cells and murine peritoneal macrophages, were determined by Western blot and/or qRT-PCR, respectively. NF-κB activation was investigated by EMSA, reporter gene assay and Western blotting. Anti-inflammatory effects of BPD were evaluated in vivo in carrageenan-induced paw oedema in rats and LPS-induced septic shock in mice.Key Results: BPD not only inhibited COX-2 activity but also reduced the expression of COX-2. In addition, BPD inhibited the expression of iNOS, TNF-α, IL-6 and IL-1β at the transcriptional level. BPD attenuated LPS-induced DNA-binding activity and the transcription activity of NF-κB; this was associated with a decrease in the phosphorylation level of inhibitory κB-α (IκB-α) and reduced nuclear translocation of NF-κB. Furthermore, BPD suppressed the formation of TGF-β-activated kinase-1 (TAK1)/TAK-binding protein1 (TAB1), which was accompanied by a parallel reduction of phosphorylation of TAK1 and IκB kinase (IKK). Pretreatment with BPD inhibited carrageenan-induced paw oedema and LPS-induced septic death.Conclusion and Implications: Taken together, our data indicate that BPD is involved in the dual inhibition of COX-2 activity and TAK1-NF-κB pathway, providing a molecular basis for the anti-inflammatory properties of BPD. [ABSTRACT FROM AUTHOR]