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Hyun Lee,1 Chin Kook Rhee,2 Byung-Jae Lee,3 Dong-Chull Choi,3 Jee-Ae Kim,4 Sang Hyun Kim,5 Yoolwon Jeong,6 Tae-Hyung Kim,7 Gyu Rak Chon,8 Ki-Suck Jung,9 Sang Haak Lee,10 David Price,11 Kwang Ha Yoo,12,* Hye Yun Park1,* 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 3Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 4Pharmaceutical Policy Evaluation Research Team, Research Institution, Health Insurance Review and Assessment Service, 5Big Data Division, Health Insurance Review and Assessment Service, Seoul, 6Division of Chronic Disease Control, Korea Centers for Disease Control and Prevention, Osong, 7Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, 8Department of Pulmonary and Critical Care Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju City, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, 10Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 11Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 12Division of Pulmonary, Allergy and Critical Care Medicine Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea *These authors contributed equally to this work Backround: Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD.Methods: Patients with mild-to-moderate COPD (≥40 years) were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012) and were linked to the national health insurance reimbursement database to obtain medical service utilization records.Results: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6%) had severe exacerbations over the 6 years (0.012/person-year). Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P

We investigated a flat-type p*-p LED composed of a p*-electrode with a local breakdown conductive channel (LBCC) formed in the p-type electrode region by applying reverse bias. By locally connecting the p*-electrode to the n-type layer via an LBCC, a flat-type LED structure is applied that can replace the n-type electrode without a mesa-etching process. Flat-type p*-p LEDs, devoid of the mesa process, demonstrate outstanding characteristics, boasting comparable light output power to conventional mesa-type n-p LEDs at the same injection current. However, they incur higher operating voltages, attributed to the smaller size of the p* region used as the n-type electrode compared to conventional n-p LEDs. Therefore, despite having comparable external quantum efficiency stemming from similar light output, flat-type p*-p LEDs exhibit diminished wall-plug efficiency (WPE) and voltage efficiency (VE) owing to elevated operating voltages. To address this, our study aimed to mitigate the series resistance of flat-type p*-p LEDs by augmenting the number of LBCCs to enhance the contact area, thereby reducing overall resistance. This structure holds promise for elevating WPE and VE by aligning the operating voltage more closely with that of mesa-type n-p LEDs. Consequently, rectifying the issue of high operating voltages in planar p*-p LEDs enables the creation of efficient LEDs devoid of crystal defects resulting from mesa-etching processes.

In somatic tissue differentiation, chromatin accessibility changes govern priming and precursor commitment towards cellular fates 1-3 . Therefore, somatic mutations are likely to alter chromatin accessibility patterns, as they disrupt differentiation topologies leading to abnormal clonal outgrowth. However, defining the impact of somatic mutations on the epigenome in human samples is challenging due to admixed mutated and wild-type cells. Here, to chart how somatic mutations disrupt epigenetic landscapes in human clonal outgrowths, we developed genotyping of targeted loci with single-cell chromatin accessibility (GoT-ChA). This high-throughput platform links genotypes to chromatin accessibility at single-cell resolution across thousands of cells within a single assay. We applied GoT-ChA to CD34 + cells from patients with myeloproliferative neoplasms with JAK2 V617F -mutated haematopoiesis. Differential accessibility analysis between wild-type and JAK2 V617F -mutant progenitors revealed both cell-intrinsic and cell-state-specific shifts within mutant haematopoietic precursors, including cell-intrinsic pro-inflammatory signatures in haematopoietic stem cells, and a distinct profibrotic inflammatory chromatin landscape in megakaryocytic progenitors. Integration of mitochondrial genome profiling and cell-surface protein expression measurement allowed expansion of genotyping onto DOGMA-seq through imputation, enabling single-cell capture of genotypes, chromatin accessibility, RNA expression and cell-surface protein expression. Collectively, we show that the JAK2 V617F mutation leads to epigenetic rewiring in a cell-intrinsic and cell type-specific manner, influencing inflammation states and differentiation trajectories. We envision that GoT-ChA will empower broad future investigations of the critical link between somatic mutations and epigenetic alterations across clonal populations in malignant and non-malignant contexts., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

MRI-guided neuro interventions require rapid, accurate, and reproducible segmentation of anatomical brain structures for identification of targets during surgical procedures and post-surgical evaluation of intervention efficiency. Segmentation algorithms must be validated and cleared for clinical use. This work introduces a methodology for shape-constrained deformable brain segmentation, describes the quantitative validation used for its clinical clearance, and presents a comparison with manual expert segmentation and FreeSurfer, an open source software for neuroimaging data analysis. ClearPoint Maestro is software for fully-automatic brain segmentation from T1-weighted MRI that combines a shape-constrained deformable brain model with voxel-wise tissue segmentation within the cerebral hemispheres and the cerebellum. The performance of the segmentation was validated in terms of accuracy and reproducibility. Segmentation accuracy was evaluated with respect to training data and independently traced ground truth. Segmentation reproducibility was quantified and compared with manual expert segmentation and FreeSurfer. Quantitative reproducibility analysis indicates superior performance compared to both manual expert segmentation and FreeSurfer. The shape-constrained methodology results in accurate and highly reproducible segmentation. Inherent point based-correspondence provides consistent target identification ideal for MRI-guided neuro interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors are employed by the clinical science and research divisions of ClearPoint Neuro and Philips. They are strictly focused on scientific aspects and have no financial or competing interests that could influence the objectivity and validity of reported work. The goal of this manuscript is to present the methodology for shape-constrained deformable brain segmentation and to describe the quantitative performance analysis used to validate the accuracy and reproducibility of segmentation results., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma., Methods: Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV 1 ]; PC 20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV 1 , forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF 25%-75% ) values obtained during MCT., Results: In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV 1 , FVC, and FEF 25%-75% were included as inputs., Conclusions: Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC 20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Capacitive deionization (CDI) is an electrochemical-based water treatment technology that has attracted attention as an effective hardness-control process. However, few systematic studies have reported the criteria for the selection of suitable electrode materials for membrane capacitive deionization (MCDI) to control hardness. In this study, the effect of electrode material characteristics on the MCDI performance for hardness control was quantitatively analyzed. The results showed that the deionization capacity and the deionization rate were affected by the specific capacitance and BET-specific surface area of the activated carbon electrode. In addition, the deionization rate also showed significant relationship with the BET specific surface area. Furthermore, it was observed that the deionization capacity and the deionization rate have a highly significant relationship with the BET specific surface area divided by the wettability performance expressed as the minimum wetting rate (MWR). These findings highlighted that the electrode material should have a large surface area and good wettability to increase the deionization capacity and the deionization rate of MCDI for hardness control. The results of this study are expected to provide effective criteria for selecting MCDI electrode materials aiming hardness control., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Revised cardiac risk index (RCRI) is widely used for surgical patients without containing age as a risk factor. We investigated age older than 65 years with respect to low-to-moderate risk of RCRI. From January 2011 to June 2019, a total of 203,787 consecutive adult patients underwent non-cardiac surgery at our institution. After excluding high-risk patients defined as RCRI score > 2, we stratified the patients into four groups according to RCRI and age (A: age < 65 with RCRI < 2, [n = 148,288], B: age ≥ 65 with RCRI < 2, [n = 42,841], C: age < 65 with RCRI = 2, [n = 5,271], and D: age ≥ 65 with RCRI = 2, [n = 5,698]). Incidence of major cardiac complication defined as a composite of cardiac death, cardiac arrest and myocardial infarction was compared. After excluding 1,689 patients with high risk (defined as RCRI score > 2), 202,098 patients were enrolled. The incidence with 95% confidence interval of major cardiac complication for A, B, C, and D groups was 0.3% (0.2-0.3), 1.1% (1.0-1.2), 1.8% (1.6-1.8), and 3.1% (2.6-3.6), respectively. In a direct comparison between B and C groups, old patients with RCRI < 2 showed a significantly lower risk compared to younger patients with RCRI = 2 (odd ratio, 0.62; 95% confidence interval, 0.50-0.78; p < 0.001). In non-cardiac surgery, the risk of age older than 65 years was shown to be comparable with low-to-moderate risk according to RCRI., (© 2023. Springer Nature Limited.)

Neurodegenerative diseases are characterized by a decline in neuronal function and structure, leading to neuronal death. Understanding the molecular mechanisms of neuronal death is crucial for developing therapeutics. MiRs are small noncoding RNAs that regulate gene expression by degrading target mRNAs or inhibiting translation. MiR dysregulation has been linked to many neurodegenerative diseases, but the underlying mechanisms are not well understood. As mitochondrial dysfunction is one of the common molecular mechanisms leading to neuronal death in many neurodegenerative diseases, here we studied miRs that modulate neuronal death caused by 1-methyl-4-phenylpyridinium (MPP + ), an inhibitor of complex I in mitochondria. We identified miR-593-5p, levels of which were increased in SH-SY5Y human neuronal cells, after exposure to MPP + . We found that intracellular Ca 2+ , but not of reactive oxygen species, mediated this miR-593-5p increase. Furthermore, we found the increase in miR-593-5p was due to enhanced stability, not increased transcription or miR processing. Importantly, we show the increase in miR-593-5p contributed to MPP + -induced cell death. Our data revealed that miR-593-5p inhibits a signaling pathway involving PTEN-induced putative kinase 1 (PINK1) and Parkin, two proteins responsible for the removal of damaged mitochondria from cells, by targeting the coding sequence of PINK1 mRNA. Our findings suggest that miR-593-5p contributes to neuronal death resulting from MPP + toxicity, in part, by impeding the PINK1/Parkin-mediated pathway that facilitates the clearance of damaged mitochondria. Taken together, our observations highlight the potential significance of inhibiting miR-593-5p as a therapeutic approach for neurodegenerative diseases., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Preoperative anxiety is an unpleasant experience that can adversely affect perioperative outcomes. Although clinical benefits of preoperative oral carbohydrate is well reported, the effect of adding chewing gum to carbohydrate loading has never been studied. We aimed to investigate the effect of adding gum-chewing to oral carbohydrates on preoperative anxiety and gastric volume in patients undergoing gynecologic surgery., Methods: One hundred and four patients were enrolled and randomized either into a carbohydrate drink group (CHD group) or CHD with gum group. The CHD group was instructed to drink 400 mL of oral carbohydrate the evening before and 200-400 mL 3 hours before surgery. The CHD with gum group was encouraged to chew gum freely during preanesthetic fasting in addition to consuming oral carbohydrates in the same manner. The primary endpoint was preoperative anxiety assessed using the Amsterdam preoperative anxiety and information scale (APAIS). The degree of patient-reported quality of recovery after surgery and gastric volume prior to general anesthesia were also compared as secondary outcomes., Results: Preoperative APAIS was lower in the CHD with gum group compared with the CHD group (16 [11.5, 20] vs. 20 [16.5, 23], p = 0.008). Patient-rated quality of recovery after surgery was also higher in the CHD with gum group and showed a significant negative correlation with preoperative APAIS score (correlation coefficient: -0.950, p = 0.001). Gastric volume were not different between the groups (0 [0-0.45] vs. 0 [0-0.22], p = 0.158)., Conclusion: The addition of gum chewing to oral carbohydrate loading during preoperative fasting was more effective in relieving preoperative anxiety than oral carbohydrate alone in women patients undergoing elective gynecologic surgery., Trial Registration: Clinical Research Information Services, CRIS identifier: KCT0005714, https://cris.nih.go.kr/cris/index.jsp., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Days alive and out of hospital (DAOH) is a simple estimator based on the number of days not in hospital within a defined period. In cases of mortality within the period, DAOH is regarded as zero. It has not been validated solely in off-pump coronary artery bypass grafting (OPCAB). This study aimed to demonstrate a correlation between DAOH and outcome of OPCAB. We identified 2211 OPCAB performed from January 2010 to August 2016. We calculated DAOH at 30 and 60 days. We generated a receiver-operating curve and compared outcomes. The median duration of hospital stay after OPCAB was 6 days. The median DAOH values at 30 and 60 days were 24 and 54 days. The estimated thresholds for 3-year mortality for DAOH at 30 and 60 days were 20 and 50 days. Three-year mortality was higher for short DAOH (1.2% vs. 5.7% and 1.1% vs. 5.6% DAOH at 30 and 60 days). After adjustment, the short DAOH 30 group showed significantly higher mortality during 3-year follow-up (hazard ratio 3.07; 95% confidence interval 1.45-6.52; p = 0.004). DAOH at 30 days after OPCAB showed a correlation with 3-year outcomes. DAOH 30 might be a reliable long-term outcome measure that can be obtained within 30 days after surgery., (© 2023. The Author(s).)

Background: Cardiac troponin I (cTnI) is a gold-standard biomarker for detecting myocardial infarction. Recently, the prognostic role of cTnI was reported for stable coronary artery disease and other chronic diseases. This study aimed to evaluate the usefulness of cTnI testing at scheduled admission of patients with comorbidities., Methods: We retrospectively enrolled patients with comorbidities who were admitted through the outpatient clinic from April 2010 to December 2018. The enrolled patients were divided into two groups depending on whether cTnI was measured at admission. The primary endpoint was the mortality rate at one year after admission. Secondary endpoints included 30-day and in-hospital mortality rates., Results: A population of 50,119 patients was divided into two groups, with 43,974 (87.8%) patients included in the no cTnI group and 6,145 (12.2%) patients included in the cTnI group. The multivariable analysis showed a reduction of mortality at one year in the cTnI group [5.9% vs. 3.8%, hazard ratio (HR) =0.78; 95% confidence interval (CI): 0.68-0.89; P<0.001]. Among 5,882 propensity score-matched pairs, this trend persisted, and the mortality rate was significantly lower in the cTnI group (5.3% vs. 3.9%, HR =0.77; 95% CI: 0.65-0.91; P=0.002). Patients with cTnI measurements taken at admission underwent cardiac evaluation and therapy more frequently., Conclusions: The measurement of cTnI at scheduled admission may affect the mortality during one year of follow-up. Further studies are needed to validate our results., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3681/coif). The authors declare no conflicts of interest., (2023 Annals of Translational Medicine. All rights reserved.)

Background: The sequential organ failure assessment (SOFA) score has been validated in various clinical situations. However, it has not been investigated during a short stay in the intensive care unit (ICU). This study aimed to evaluate the association between the SOFA score and outcomes in patients who were monitored for less than one day after non-cardiac surgery. Methods: From a total of 203,787 consecutive adult patients who underwent non-cardiac surgery between January 2011 and June 2019, we selected 17,714 who were transferred to the ICU immediately after surgery and stayed for less than 24 h. Patients were divided according to quartile value and change between the initial and follow-up levels of SOFA score. Results: Three-year mortality tended to increase with a higher initial SOFA score (11.7%, 11.8%, 15.1%, and 17.8%, respectively). The patients were divided according to changes in the SOFA score at the midnight postoperative follow-up check: 16,176 (91.3%) in the stable group and 1538 (8.7%) in the worsened group. The worsened group showed significantly higher three-year mortality and complications (13.2% vs. 18.6%; HR [hazard ratio]: 1.236; 95% CI [confidence interval]: 1.108−1.402; p ≤ 0.0021 for three-year mortality and 3.8% vs. 9.1%; HR: 2.13; 95% CI: 1.73−2.60; p < 0.001 for acute kidney injury). Conclusions: The SOFA score during a short stay in the ICU after non-cardiac surgery showed an association with mortality. The change in SOFA score may need to be considered at discharge from the ICU.

Background: Ear, nose, and throat involvement are common in eosinophilic granulomatosis with polyangiitis (EGPA). Among otologic manifestation, middle ear effusion (MEE) is less recognized but a problematic condition as it may progress to hearing impairment when left untreated. This study aimed to evaluate the characteristics, risk factors and clinical outcomes of MEE in EGPA patients., Methods: This is a case-control study of patients who were diagnosed and treated for EGPA from January 1995 to November 2018. Patients with ear symptoms (ear fullness, ear discharge, tinnitus or hearing loss) were assessed by otologists and were included in the case group (n = 23) if clinically relevant. The other patients without MEE were included in the control group (n = 52). Risk of MEE was calculated using the Cox proportional-hazard model., Results: During median follow-up of 9.9 years, 23 (30.7%) out of 75 patients had MEE. In MEE group, 12 (52.2%) patients had hearing loss; conductive type in 10 (10/12, 83.3%) and mixed type in two (2/12, 16.7%). In multivariable regression analysis, major organ involvement at diagnosis (adjusted hazard ratio [aHR] 65.4; 95% confidence interval [CI], 1.50-2838.39; P = 0.030] , early onset of ear symptom after systemic therapy (< 6 months) (aHR 40.0; 95% CI, 1.35-1183.43; P = 0.033) and continuing the maintenance steroid without cessation (aHR 8.59; 95% CI, 1.13-65.42; P = 0.038) were independently associated with a risk of MEE. To control MEE, 16 (69.6%) patients had to increase maintenance steroid dose and 9 (39.1%) patients experienced recurrent MEE whenever maintenance dose was tapered., Conclusions: MEE is a common but frequently neglected condition in EGPA which is often intractable. The maintenance steroid dose should be adequately adjusted to control MEE and to prevent from progressive hearing loss. Novel biologic agents possibly have a role in controlling MEE in EGPA., (© 2022. The Author(s).)

The current cut-off value for diagnosing exercise-induced bronchoconstriction (EIB) in adults-percent fall in FEV1 (ΔFEV1) ≥ 10% after exercise challenge test (ECT)-has low specificity and weak evidences. Therefore, this study aimed to identify the cut-off value for EIB that provides the highest diagnostic sensitivity and specificity. Participants who underwent the ECT between 2007 and 2018 were categorized according to ΔFEV1: definite EIB (ΔFEV1 ≥ 15%), borderline (10% ≤ ΔFEV1 < 15%), and normal (ΔFEV1 < 10%). Distinct characteristics of the definite EIB group were identified and explored in the borderline EIB group. A receiver operating characteristic curve was plotted to determine the optimal cut-off value. Of 128 patients, 60 were grouped as the definite EIB group, 23 as the borderline group, and 45 as the normal group. All participants were men, with a median age of 20 years (interquartile range [IQR:] 19-23 years). The definite EIB group exhibited wheezing on auscultation (P < 0.001), ΔFEV1/FVC ≥ 10% (P < 0.001), and ΔFEF25-75% ≥ 25% (P < 0.001) compared to other groups. Eight (8/23, 34.8%) patients in the borderline group had at least one of these features, but the trend was more similar to that of the normal group than the definite EIB group. A cut-off value of ΔFEV1 ≥ 13.5% had a sensitivity of 98.5% and specificity of 93.5% for EIB. Wheezing on auscultation, ΔFEV1/FVC ≥ 10%, and ΔFEF25-75% ≥ 25% after ECT may be useful for the diagnosis of EIB, particularly in individuals with a ΔFEV1 of 10-15%. For EIB, a higher cut-off value, possibly ΔFEV1 ≥ 13.5%, should be considered as the diagnostic criterion., Competing Interests: The authors have declared that no competing interests exist.

In our ongoing search for new secondary metabolites from fungal strains, one novel compound ( 1 ) and nine known compounds ( 2-10 ) were isolated from the EtOAc-soluble layer of the culture broth of Panus rudis . The culture broth of P. rudis was extracted in acetone and fractionated by solvent partition; column chromatography using silica gel, Sephadex LH-20, and Sephadex G-10; MPLC; and HPLC. The structures of isolated compounds were elucidated by one- and two-dimensional NMR and LC-ESI-mass measurements. One new compound, panepoxydiol ( 1 ), and nine known compounds, ( E )-3-(3-hydroxy-3-methylbut-1-en-1-yl)-7-oxabicyclo[4.1.0]hept-3-ene-2,5-diol ( 2 ), isopanepoxydone ( 3 ), neopanepoxydone ( 4 ), panepoxydone ( 5 ), panepophenanthrin ( 6 ), 4-hydroxy-2,2-dimethyl-6-methoxychromane ( 7 ), 6-hydroxy-2,2-dimethyl-3-chromen ( 8 ), 2,2-dimethyl-6-methoxychroman-4-one ( 9 ), 3,4-dihydroxy-2,2-dimethyl-6-methoxychromane ( 10 ), were isolated from the culture broth of P. rudis . This is the first report of isolation of a new compound panepoxydiol ( 1 ) and nine other chemical constituents ( 2 - 5 , 7 - 10 ) from the culture broth of P. rudis ., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Thirteen ( Z )-2-(substituted benzylidene)benzimidazothiazolone analogs were synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. Among the compounds synthesized, compounds 1 - 3 showed greater inhibitory activity than kojic acid (IC 50 = 18.27 ± 0.89 μM); IC 50 = 3.70 ± 0.51 μM for 1 ; IC 50 = 3.05 ± 0.95 μM for 2 ; and IC 50 = 5.00 ± 0.38 μM for 3 , and found to be competitive tyrosinase inhibitors. In silico molecular docking simulations demonstrated that compounds 1 - 3 could bind to the catalytic sites of tyrosinase. Compounds 1 - 3 inhibited melanin production and cellular tyrosinase activity in a concentration-dependent manner. Notably, compound 2 dose-dependently scavenged ROS in B16F10 cells. Furthermore, compound 2 downregulated the protein kinase A (PKA)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways, which led to a reduction in microphthalmia-associated transcription factor (MITF) expression, and decreased tyrosinase, tyrosinase related protein 1 (TRP1), and TRP2 expression, resulting in anti-melanogenesis activity. Hence, compound 2 may serve as an anti-melanogenic agent against hyperpigmentation diseases.

Background: Data on the clinical characteristics of asthma patients including utilization of medical facilities, disease management, and healthcare costs by types of health care are insufficient., Methods: We evaluated data on 729,343 asthma patients from the Health Insurance Review and Assessment Service (HIRA) database of Korea between July 2013 and June 2014., Results: Most asthma patients were treated via primary care (81.7%), followed by tertiary (17.8%) and secondary (0.5%) care. Patients requiring secondary or tertiary care exhibited more comorbidities and exacerbations than those treated via primary care, and utilized more medical facilities (associated with higher medical costs). The prescription rate of leukotriene receptor antagonists (LTRAs) was relatively high for those receiving all types of health care, ranging from 62% to 78%. However, the prescription rate of inhalants containing corticosteroids was significantly lower in patients treated via primary care than those receiving secondary or tertiary care (P<0.001). In addition, pulmonary function testing (PFT) was performed less often in patients treated via primary care than in those receiving secondary or tertiary care (P<0.001)., Conclusions: Most patients with asthma were treated via primary care; however, those receiving secondary or tertiary care exhibited substantial utilization of medical facilities with high costs. Diagnostic measures and the prescription of inhalants containing corticosteroids in primary care require urgent attention., Competing Interests: Conflicts of Interest: Chin Kook Rhee has received consulting/lecture fees from MSD, AstraZeneca, Novartis, GSK, Takeda, Mundipharma, Sandoz, Boehringer-Ingelheim, and Teva-Handok. Hye Yun Park has received lecture fees from AstraZeneca, Novartis, and Boehringer-Ingelheim. The other authors have no conflicts of interest to declare.

Background and Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis accompanied by asthma, eosinophilia, and eosinophilic inflammation of various tissues including the peripheral nerves. This study investigated the clinical course and long-term outcomes of peripheral neuropathy in patients with EGPA., Methods: Seventy-one patients with physician-diagnosed EGPA were identified at Samsung Medical Center between January 1995 and April 2014. Sixty-one of these patients were followed-up for more than 1 year and received corticosteroid therapy with or without intravenous cyclophosphamide pulse therapy for 6 to 18 months. Medical records of the 61 patients including demographic data, clinical features, laboratory and pathological findings, treatments, and outcomes were reviewed., Results: Peripheral neuropathy as a manifestation of EGPA was present in 46 (75%) of the 61 patients. The mean follow-up duration of the patients with neuropathy was 6.4 years (range 1.2-18.8 years). The scores on the neurological functional disability scale before and after the combination treatment with corticosteroid and cyclophosphamide were 2.43±0.86 and 0.54±0.95 (mean±SD; p<0.001), respectively. The peripheral neuropathy relapsed in one patient., Conclusions: The long-term clinical outcome of peripheral neuropathy in patients with EGPA receiving initial corticosteroid and cyclophosphamide combination therapy was favorable with a very low relapse rate., Competing Interests: The authors have no financial conflicts of interest.

We report a simple and mass-scalable approach for thin MoS2 films via RF sputtering combined with the post-deposition annealing process. We have prepared as-sputtered film using a MoS2 target in the sputtering system. The as-sputtered film was subjected to post-deposition annealing to improve crystalline quality at 700 °C in a sulfur and argon environment. The analysis confirmed the growth of continuous bilayer to few-layer MoS2 film. The mobility value of ~29 cm(2)/Vs and current on/off ratio on the order of ~10(4) were obtained for bilayer MoS2. The mobility increased up to ~173-181 cm(2)/Vs, respectively, for few-layer MoS2. The mobility of our bilayer MoS2 FETs is larger than any previously reported values of single to bilayer MoS2 grown on SiO2/Si substrate with a SiO2 gate oxide. Moreover, our few-layer MoS2 FETs exhibited the highest mobility value ever reported for any MoS2 FETs with a SiO2 gate oxide. It is presumed that the high mobility behavior of our film could be attributed to low charged impurities of our film and dielectric screening effect by an interfacial MoOxSiy layer. The combined preparation route of RF sputtering and post-deposition annealing process opens up the novel possibility of mass and batch production of MoS2 film.

Mitochondrial dysfunction is one of the major contributors to neurodegenerative disorders including Parkinson disease. The mitochondrial permeability transition pore is a protein complex located on the mitochondrial membrane. Under cellular stress, the pore opens, increasing the release of pro-apoptotic proteins, and ultimately resulting in cell death. MicroRNA-7 (miR-7) is a small non-coding RNA that has been found to exhibit a protective role in the cellular models of Parkinson disease. In the present study, miR-7 was predicted to regulate the function of mitochondria, according to gene ontology analysis of proteins that are down-regulated by miR-7. Indeed, miR-7 overexpression inhibited mitochondrial fragmentation, mitochondrial depolarization, cytochrome c release, reactive oxygen species generation, and release of mitochondrial calcium in response to 1-methyl-4-phenylpyridinium (MPP(+)) in human neuroblastoma SH-SY5Y cells. In addition, several of these findings were confirmed in mouse primary neurons. Among the mitochondrial proteins identified by gene ontology analysis, the expression of voltage-dependent anion channel 1 (VDAC1), a constituent of the mitochondrial permeability transition pore, was down-regulated by miR-7 through targeting 3'-untranslated region of VDAC1 mRNA. Similar to miR-7 overexpression, knockdown of VDAC1 also led to a decrease in intracellular reactive oxygen species generation and subsequent cellular protection against MPP(+). Notably, overexpression of VDAC1 without the 3'-UTR significantly abolished the protective effects of miR-7 against MPP(+)-induced cytotoxicity and mitochondrial dysfunction, suggesting that the protective effect of miR-7 is partly exerted through promoting mitochondrial function by targeting VDAC1 expression. These findings point to a novel mechanism by which miR-7 accomplishes neuroprotection by improving mitochondrial health., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Drug-induced anaphylaxis is a big pitfall in patients receiving antineoplastic chemotherapy. We report a case of lung cancer patient who experienced two near-fatal anaphylactic reactions that resulted from paclitaxel and multivitamin, seperately. Recurrent severe reactions to different agents led to further investigation to which material the patient was hypersensitive. The skin prick test revealed sensitization to cremophor, which is a commonly used emulsifying agent. This case emphasizes the importance of correctly identifying the culprit drug of anaphylaxis to avoid potentially fatal reaction.

In this paper a novel filtering scheme combined with a lighting method is proposed for defect detection in steel surfaces. A steel surface has non-uniform brightness and various shaped defects, which cause difficulties in defect detection. To solve this problem we propose a sub-optimal filtering that is combined with a switching-lighting method. First, dual-light switching lighting (DLSL) is explained, which decreases the effect of non-uniformity of surface brightness and improves the detection accuracy. By using the DLSL method, defects are represented as alternated black and white patterns regardless of the size, shape, or orientation of defects. Therefore, defects can be detected by finding alternated black and white patterns. Second, we propose a scheme for detecting defects in steel-surface images acquired using the DLSL method. The presence of scales strongly affects the optical properties of the surface. Moreover, the textures of steel-plate images vary greatly because of the temperature and grade of steel. Therefore, conventional filter-design methods are not effective for different image textures. A sub-optimal scheme based on an optimized general-finite impulse-response filter is also proposed. Finally, experimental results conducted on steel-surface images from an actual steel-production line show the effectiveness of the proposed algorithm.

Purpose: Toxocariasis is the most common cause of peripheral blood eosinophilia in Korea and produces eosinophilic infiltration in various organs, including the lung. However, the prevalence of toxocariasis in the general population is rarely reported., Methods: We investigated the seroprevalence of Toxocara larval antibody among asymptomatic people who attended Samsung Medical Center for a health checkup, including low-dose chest computed tomography (CT) between March 2012 and December 2013. A total of 633 people (400 men and 233 women) were prospectively recruited., Results: The Toxocara-seropositive rate was 51.2% using the current cutoff value based on Toxocara enzyme-linked immunosorbent assay (ELISA) (67.0% for men and 24.0% for women). In the multivariate-adjusted model, age (odds ratio [OR], 1.08; 95% confidence intervals [CI], 1.04-1.11), male sex (OR, 3.47; 95% CI, 2.26-5.33), rural residence (OR, 1.55; 95% CI, 1.05-2.30), and history of raw liver intake (OR, 8.52; 95% CI, 3.61-20.11) were significantly associated with Toxocara seropositivity. When subjects were divided into 3 groups using cutoff values base on weak positive and strong positive control optical densities (ODs), the ORs for peripheral blood eosinophilia and serum hyperIgEaemia were 0.31 (95% CI, 0.02-2.89) in the weakpositive group and 36.64 (95% CI, 11.73-111.42) in the strong positive group compared to the seronegative group. Similarly, ORs for the solid nodule with surrounding halo were 2.54 (95% CI, 0.60-10.84) in the weak positive group and 15.08 (95 CI 4.09-55.56) in the strong positive group compared to the seronegative group., Conclusions: The study indicated that the Toxocara-seropositive rate obtained by using the current cutoff value based on ELISA was high in the asymptomatic population in Korea. The results of this study suggest that active toxocariasis may be more frequently seen in the Toxocara-strong positive group than in the Toxocara-weak positive group.

This study was performed to compare the 2 different portable devices measuring fractional exhaled nitric oxide (FeNO) and to see the correlation between FeNO and induced sputum eosinophil count (ISE). Forty consecutive subjects clinically suspected to have asthma underwent FeNO measurement by NIOX-MINO® and NObreath® concurrently. All also had induced sputum analysis, methacholine provocation test or bronchodilator response test, and spin prick test. Agreement between the 2 devices was evaluated. The correlation between FeNO and ISE was assessed, as well as the cut-off level of FeNO to identify ISE ≥3%. The intraclass correlation coefficient (ICC) between FeNO levels measured by NIOX-MINO® (FeNO(NIOX-MINO)) and NObreath® (FeNO(NObreath)) was 0.972 with 95% confidence interval of 0.948-0.985. The 95% limits of agreement were -28.9 to 19.9 ppb. The correlation coefficient between ISE and FeNO(NIOX-MINO) was 0.733 (P<0.001), and 0.751 between ISE and FeNO(NObreath) (P<0.001). The ROC curve found that the FeNO(NIOXMINO) of 37.5 ppb and the FeNO(NObreath) of 36.5 ppb identified ISE ≥3% with 90% sensitivity and 81% specificity. Age, sex, body mass index, smoking history, atopy, and the presence of asthma did not affect the FeNO level and its correlation with ISE. The NIOX-MINO ® and NObreath® agree with each other to a high degree. Both devices showed close correlation with ISE with similar cut-off value in identifying ISE ≥3%.

Parkinson disease is associated with decreased activity of the mitochondrial electron transport chain. This defect can be recapitulated in vitro by challenging dopaminergic cells with 1-methyl-4-phenylpyridinium (MPP(+)), a neurotoxin that inhibits complex I of electron transport chain. Consequently, oxidative phosphorylation is blocked, and cells become dependent on glycolysis for ATP production. Therefore, increasing the rate of glycolysis might help cells to produce more ATP to meet their energy demands. In the present study, we show that microRNA-7, a non-coding RNA that protects dopaminergic neuronal cells against MPP(+)-induced cell death, promotes glycolysis in dopaminergic SH-SY5Y and differentiated human neural progenitor ReNcell VM cells, as evidenced by increased ATP production, glucose consumption, and lactic acid production. Through a series of experiments, we demonstrate that targeted repression of RelA by microRNA-7, as well as subsequent increase in the neuronal glucose transporter 3 (Glut3), underlies this glycolysis-promoting effect. Consistently, silencing Glut3 expression diminishes the protective effect of microRNA-7 against MPP(+). Further, microRNA-7 fails to prevent MPP(+)-induced cell death when SH-SY5Y cells are cultured in a low glucose medium, as well as when differentiated ReNcell VM cells or primary mouse neurons are treated with the hexokinase inhibitor, 2-deoxy-d-glucose, indicating that a functional glycolytic pathway is required for this protective effect. In conclusion, microRNA-7, by down-regulating RelA, augments Glut3 expression, promotes glycolysis, and subsequently prevents MPP(+)-induced cell death. This protective effect of microRNA-7 could be exploited to correct the defects in oxidative phosphorylation in Parkinson disease., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Mounting evidence suggests that microRNA (miR) dysregulation contributes to neurodegenerative disorders including Parkinson's disease (PD). MiR-34b and miR-34c have been previously shown to be down-regulated in the brains of patients with PD. Here, we demonstrate that miR-34b and miR-34c repress the expression of α-synuclein (α-syn), a key protein in PD pathogenesis. Inhibition of miR-34b and miR-34c expression in human dopaminergic SH-SY5Y cells increased α-syn levels and stimulated aggregate formation. Additionally, a single nucleotide polymorphism (SNP) in the 3'-UTR of α-syn was found to lower the miR-34b-mediated repression of the protein. Our results suggest that down-regulation of miR-34b and miR-34c in the brain, as well as an SNP in the 3'-UTR of α-syn can increase α-syn expression, possibly contributing to PD pathogenesis., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Secretory clusterin (sCLU), an anti-apoptotic protein, is overexpressed in many tumors and enhances tumorigenesis and chemo-resistance. However, the regulation mechanism controlling the sCLU maturation process or activity remains undetermined. In this study, we found PACAP as a negative regulator of CLU. Overexpression of the PACAP gene in cervical cancer cell lines lacking PACAP expression significantly inhibited cell growth and induced apoptosis. We further demonstrated that interaction of PACAP with CLU significantly downregulated CLU expression and secretion, inhibited the Akt-Raf-ERK pathway, and suppressed the growth of human tumor xenografts in nude mice. This novel inhibitory function of PACAP may be applicable for developing novel molecular therapies for tumors with increased sCLU expression., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Mitochondrial complex I impairment in PD is modeled in vitro by the susceptibility of dopaminergic neurons to the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+). In the present study, we demonstrate that microRNA-7 (miR-7), which is expressed in tyrosine hydroxylase-positive nigral neurons in mice and humans, protects cells from MPP+-induced toxicity in dopaminergic SH-SY5Y cells, differentiated human neural progenitor ReNcell VM cells, and primary mouse neurons. RelA, a component of nuclear factor-κB (NF-κB), was identified to be downregulated by miR-7 using quantitative proteomic analysis. Through a series of validation experiments, it was confirmed that RelA mRNA is a target of miR-7 and is required for cell death following MPP+ exposure. Further, RelA mediates MPP+-induced suppression of NF-κB activity, which is essential for MPP+-induced cell death. Accordingly, the protective effect of miR-7 is exerted through relieving NF-κB suppression by reducing RelA expression. These findings provide a novel mechanism by which NF-κB suppression, rather than activation, underlies the cell death mechanism following MPP+ toxicity, have implications for the pathogenesis of PD, and suggest miR-7 as a therapeutic target for this disease., (Copyright © 2014 the authors 0270-6474/14/3412725-13$15.00/0.)

Presently, product inspection based on vision systems is an important part of the steel-manufacturing industry. In this work, we focus on the detection of seam cracks in the edge region of steel plates. Seam cracks are generated in the vertical direction, and their width range is 0.2-0.6 mm. Moreover, the gray values of seam cracks are only 20-30 gray levels lower than those of the neighboring surface. Owing to these characteristics, we propose a new algorithm for detecting seam cracks using a Gabor filter combination method. To enhance the performance, we extracted features of seam cracks and employed a support vector machine classifier. The experimental results show that the proposed algorithm is suitable for detecting seam cracks.

Purpose: Long-acting β2 agonists (LABA) may mask ongoing bronchial inflammation, leaving asthmatic patients at greater risk of severe complications. The aim of this study was to compare the effect of combination therapy using low-dose inhaled corticosteroids (ICS) plus LABA on airway inflammation in asthma to the effect of medium-dose ICS alone., Methods: Twenty-four patients with asthma not controlled by low-dose (400 µg per day) budesonide alone were enrolled in this prospective crossover study. Patients were randomized into 2 treatment phases: one receiving medium-dose (800 µg per day) budesonide (ICS phase), and the other receiving a combination therapy of low-dose budesonide/formoterol (360 µg/9 µg per day) delivered by a single inhaler (LABA phase). Each treatment phase lasted for 6 week, after which patients were crossed over. Asthma symptoms, lung function, and airway inflammation were compared between the 2 phases., Results: Twenty-three patients completed the study; adequate sputum samples were collected from 17 patients. Asthma symptoms and lung function remained similar between the 2 phases. However, the mean sputum eosinophil percentage was higher in the LABA phase than in the ICS phase (5.07±3.82% vs. 1.02±1.70%; P<0.01). Sputum eosinophilia (≥3%) was more frequently observed in the LABA phase than in the ICS phase (six vs. two)., Conclusion: Addition of LABA may mask airway eosinophilic inflammation in asthmatic patients whose symptoms are not controlled with low-dose ICS.

Although idiopathic hypereosinophilic syndrome(IHES) commonly involves the lung, it is rarely associated with acute respiratory distress syndrome (ARDS). Here we describe a case of IHES presented in conjunction with ARDS. A 37-year-old male visited the emergency department at Samsung Medical Center, Seoul, Korea, with a chief complaint of dyspnea. Blood tests showed profound peripheral eosinophilia and thrombocytopenia. Patchy areas of consolidation with ground-glass opacity were noticed in both lower lung zones on chest radiography. Rapid progression of dyspnea and hypoxia despite supplement of oxygen necessitated the use of mechanical ventilation. Eosinophilic airway inflammation was subsequently confirmed by bronchoalveolar lavage, leading to a diagnosis of IHES. High-dose corticosteroids were administered, resulting in a dramatic clinical response.

Acupuncture (AP) has been used worldwide to relieve pain. However, the mechanism of action of AP is poorly understood. Here, we found that AP relieved neuropathic pain (NP) by inhibiting Jun-N-terminal kinase (JNK) activation in astrocytes after spinal cord injury (SCI). After contusion injury which induces the below-level (L4-L5) NP, Shuigou (GV26) and Yanglingquan (GB34) acupoints were applied. At 31 d after injury, both mechanical allodynia and thermal hyperalgesia were significantly alleviated by AP applied at GV26 and GB34. Immunocytochemistry revealed that JNK activation was mainly observed in astrocytes after injury. AP inhibited JNK activation in astrocytes at L4-L5 level of spinal cord. The level of p-c-Jun known, a downstream molecule of JNK, was also decreased by AP. In addition, SCI-induced GFAP expression, a marker for astrocytes, was decreased by AP as compared to control groups. Especially, the number of hypertrophic, activated astrocytes in laminae I-II of dorsal horn at L4-5 was markedly decreased by AP treatment when compared with vehicle and simulated AP-treated groups. When animals treated with SP600125, a specific JNK inhibitor, after SCI, both mechanical allodynia and thermal hyperalgesia were significantly attenuated by the inhibitor, suggesting that JNK activation is likely involved in SCI-induced NP. Also, the expression of chemokines which is known to be mediated through JNK pathway was significantly decreased by AP and SP600125 treatment. Therefore, our results indicate that analgesic effect of AP is mediated in part by inhibiting JNK activation in astrocytes after SCI.

Research has identified distinct neuronal circuits within the basolateral amygdala (BLA) that differentially mediate fear expression versus inhibition; however, molecular markers of these populations remain unknown. Here we examine whether optogenetic activation of a cellular subpopulation, which may correlate with the physiologically identified extinction neurons in the BLA, would differentially support fear conditioning versus fear inhibition/extinction. We first molecularly characterized Thy1-channelrhodopsin-2 (Thy1-ChR2-EYFP)-expressing neurons as a subpopulation of glutamatergic pyramidal neurons within the BLA. Optogenetic stimulation of these neurons inhibited a subpopulation of medial central amygdala neurons and shunted excitation from the lateral amygdala. Brief activation of these neurons during fear training disrupted later fear memory in male mice. Optogenetic activation during unreinforced stimulus exposure enhanced extinction retention, but had no effect on fear expression, locomotion, or open-field behavior. Together, these data suggest that the Thy1-expressing subpopulation of BLA pyramidal neurons provide an important molecular and pharmacological target for inhibiting fear and enhancing extinction and for furthering our understanding of the molecular mechanisms of fear processing.

The medial prefrontal cortex (mPFC) is known to regulate executive decisions and the expression of emotional memories. More specifically, the prelimbic cortex (PL) of the mPFC is implicated in driving emotional responses via downstream targets including the nucleus accumbens and amygdala, but mechanisms are yet to be fully understood. Therefore, we investigated whether prelimbic cortical brain-derived neurotrophic factor (BDNF) signaling through the high-affinity tyrosine kinase receptor B (TrkB) receptor may serve as a molecular mechanism underlying emotional memory encoding. Here, we utilized viral-mediated inducible bdnf deletion within the PL, as well as TrkB(F616A) mutant mice, wherein TrkB receptor point mutation results in its being highly sensitive to inhibition by small PP1-derivative molecules, serving as a specific TrkB inhibitor. The site-specific TrkB antagonism and viral-mediated bdnf deletion within the PL resulted in deficits in both cocaine-dependent associative learning and fear expression. Deficiencies were rescued by the novel TrkB agonist 7,8-dihydroxyflavone, indicating that PL BDNF expression and downstream signaling through the TrkB receptor are required for memory formation in both appetitive and aversive domains.

Thromboembolism is one of the most critical complications of hypereosinophilic syndrome (HES). We report here a case of multi-organ infarctions related to HES. A 23-year-old woman was referred to our hospital with hemoptysis. Not only pulmonary, but also renal and splenic infarctions were detected on computed tomography images. Blood tests showed profound peripheral eosinophilia. She was diagnosed with HES with disseminated intravascular coagulation (DIC). We initiated infusion of corticosteroids, which effectively suppressed peripheral eosinophilia. However, consumptive coagulopathy did not improve and intracerebral hemorrhage related to thrombosis then developed. Addition of interferon-alpha resulted in the correction of the DIC associated with HES.

The aim of this study is to ascertain the relationship between ingestion of raw cow liver and Toxocara canis infection. A total of 150 apparently healthy adults were divided into 2 groups; 1 group consisted of 86 adults with positive results of Toxocara ELISA, and the other group of 64 adults with negative results. One researcher collected the history of ingestion of raw cow liver within 1 year and recent history of keeping dogs. Among 86 seropositive adults for T. canis, 68 (79.1%) had a recent history of ingestion of raw cow liver. Multivariate statistical analysis showed that a recent ingestion of raw cow liver and keeping dogs were related to an increased risk of toxocariasis (odds ratios, 4.4 and 3.7; and 95% confidence intervals, 1.9-10.2 and 1.2-11.6, respectively). A recent history of ingestion of raw cow liver and keeping dogs was significantly associated with toxocariasis.

The unnatural isotope fluorine-18 ((18)F) is used as a positron emitter in molecular imaging. Currently, many potentially useful (18)F-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of (18)F requires rapid syntheses for which [(18)F]fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional [(18)F]fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic (18)F-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging.

Presently, product inspection for quality control is becoming an important part in the steel manufacturing industry. In this paper, we propose a vision-based method for detection of pinholes in the surface of scarfed slabs. The pinhole is a very tiny defect that is 1-5 mm in diameter. Because the brightness in the surface of a scarfed slab is not uniform and the size of a pinhole is small, it is difficult to detect pinholes. To overcome the above-mentioned difficulties, we propose a new defect detection algorithm using a Gabor filter and morphological features. The Gabor filter was used to extract defective candidates. The morphological features are used to identify the pinholes among the defective candidates. Finally, the experimental results show that the proposed algorithm is effective to detect pinholes in the surface of the scarfed slab.

Individuals often eat calorically dense, highly palatable "comfort" foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect. Together, these results suggest that the palatable/rewarding properties of sucrose are necessary and sufficient for stress dampening. In support of this finding, another type of natural reward (sexual activity) similarly reduces stress responses. Ibotenate lesions of the basolateral amygdala (BLA) prevent stress dampening by sucrose, suggesting that neural activity in the BLA is necessary for the effect. Moreover, sucrose intake increases mRNA and protein expression in the BLA for numerous genes linked with functional and/or structural plasticity. Lastly, stress dampening by sucrose is persistent, which is consistent with long-term changes in neural activity after synaptic remodeling. Thus, natural rewards, such as palatable foods, provide a general means of stress reduction, likely via structural and/or functional plasticity in the BLA. These findings provide a clearer understanding of the motivation for consuming palatable foods during times of stress and influence therapeutic strategies for the prevention and/or treatment of obesity and other stress-related disorders.

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils, was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation, which is dependent on both Th1 and Th17 cell responses.

Gummy stem blight is a major foliar disease of muskmelon (Cucumis melo L.). In this study, morphological characteristics and rDNA internal transcribed spacer (ITS) sequences were analyzed to identify the causal organism of this disease. Morphological examination of the Jeonbuk isolate revealed that the percentage of monoseptal conidia ranged from 0% to 10%, and the average length × width of the conidia was 70 (± 0.96) × 32.0 (± 0.15) µm on potato dextrose agar. The BLAST analysis showed nucleotide gaps of 1/494, 2/492, and 1/478 with identities of 485/492 (98%), 492/494 (99%), 491/494 (99%), and 476/478 (99%). The similarity in sequence identity between the rDNA ITS region of the Jeonbuk isolate and other Didymella bryoniae from BLAST searches of GenBank was 100% and was 95.0% within the group. Nucleotide sequences of the rDNA ITS region from pure culture ranged from 98.2% to 99.8%. Phylogenetic analysis with related species of D. bryoniae revealed that D. bryoniae is a monophyletic group distinguishable from other Didymella spp., including Ascochyta pinodes, Mycosphaerella pinodes, M. zeae-maydis, D. pinodes, D. applanata, D. exigua, D. rabiei, D. lentis, D. fabae, and D. vitalbina. Phylogenetic analysis, based on rDNA ITS sequence, clearly distinguished D. bryoniae and Didymella spp. from the 10 other species studied. This study identified the Jeonbuk isolate to be D. bryoniae.

Purpose: Drug rash with eosinophilia and systemic symptoms (DRESS) and the Stevens-Johnson syndrome (SJS) are both severe drug reactions. Their pathogenesis and clinical features differ. This study compared the causes and clinical features of SJS and DRESS., Methods: We enrolled 31 patients who were diagnosed with DRESS (number=11) and SJS (number=20). We retrospectively compared the clinical and laboratory data of patients with the two disorders., Results: In both syndromes, the most common prodromal symptoms were itching, fever, and malaise. The liver was commonly involved in DRESS. The mucosal membrane of the oral cavity and eyes was often affected in SJS. The most common causative agents in both diseases were antibiotics (DRESS 4/11 (37%), SJS 8/20 (40%)), followed by anticonvulsants (DRESS 3/11 (27%), SJS 7/20 (35%)). In addition, dapsone, allopurinol, clopidogrel, sulfasalazine and non-steroidal anti-inflammatory drugs (NSAIDs) were sporadic causes., Conclusions: The most common causes of DRESS and SJS were antibiotics, followed by anticonvulsants, NSAIDs and sulfonamides. The increase in the use of antibiotics in Korea might explain this finding.

In the medial prefrontal cortex, the prelimbic area is emerging as a major modulator of fear behavior, but the mechanisms remain unclear. Using a selective neocortical knockout mouse, virally mediated prelimbic cortical-specific gene deletion, and pharmacological rescue with a TrkB agonist, we examined the role of a primary candidate mechanism, BDNF, in conditioned fear. We found consistently robust deficits in consolidation of cued fear but no effects on acquisition, expression of unlearned fear, sensorimotor function, and spatial learning. This deficit in learned fear in the BDNF knockout mice was rescued with systemic administration of a TrkB receptor agonist, 7,8-dihydroxyflavone. These data indicate that prelimbic BDNF is critical for consolidation of learned fear memories, but it is not required for innate fear or extinction of fear. Moreover, use of site-specific, inducible BDNF deletions shows a powerful mechanism that may further our understanding of the pathophysiology of fear-related disorders.

Atopic myelitis is defined as myelitis with atopic diasthesis but the cause is still unknown. Toxocariasis is one of the common causes of hyperIgEaemia that may lead to neurologic manifestations. The purpose of this study was to evaluate the sero-prevalence of Toxocara specific IgG Ab among the atopic myelitis patients. We evaluated the medical records of 37 patients with atopic myelitis whose conditions were diagnosed between March 2001 and August 2007. Among them, the 33 sera were analyzed for specific serum IgG Ab to Toxocara excretory-secretory antigens (TES). All of 37 patients had hyperIgEaemia. Specific IgE to D. pteronyssinus and D. farinae was detected in 22 (64.7%) and 34 (100%) patients, respectively, of the 34 patients. Thirty-one of 33 patients (93.9%) were found to be positive by TES IgG enzyme-linked immunosorbent assay (ELISA). Based on the image findings of eosinophilic infiltrations in the lung and liver, 8 patients had positive results. These results inferred that the prevalence of toxocariasis was high in patients with atopic myelitis. Our results suggest that toxocariasis might be an important cause of atopic myelitis and Toxocara ELISA is essential for evaluating the causes of atopic myelitis.