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Kuo-Feng Hua,1,2,* Hsien-Ta Hsu,3,4,* May-Shu Huang,5,6 Hsiao-Wen Chiu,1 Wei-Ting Wong,1 Chien-Hsiu Peng,1 Yu-Bei Lin,1 Ann Chen,7 Chien-Chun Wang,8,9 Chung-Hua Hsu,10,11 Chun-Hsien Wu,12 Wen-Yu Lin,1,12 Chen-Lung Ho,13 Lan-Hui Li14 1Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan; 2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; 3Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 4School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; 5Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 6Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan; 8Infectious Disease Division, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 9Kunming Prevention and Control Center, Taipei City Hospital, Taipei, Taiwan; 10Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 11Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 12Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 13Division of Wood Cellulose, Taiwan Forestry Research Institute, Taipei, Taiwan; 14Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Lan-Hui Li, Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, 100, Kunming Street, Wanhua District, Taipei City, 108203, Taiwan, Tel +886-2-23703739 # 1438, Fax +886-2-23885259, Email A1525@tpech.gov.twPurpose: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1β, presents a target for disease management. Neisseria gonorrhoeae causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in N. gonorrhoeae-infected macrophages.Methods: Honokiol’s impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular H2O2 and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-H2DCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC2(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of N. gonorrhoeae was examined through an in vitro colony-forming units assay.Results: Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1β, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in N. gonorrhoeae-infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of H2O2 and the phosphorylation of ERK1/2 in N. gonorrhoeae-infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the N. gonorrhoeae-mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by N. gonorrhoeae independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against N. gonorrhoeae.Conclusion: Honokiol inhibits the NLRP3 inflammasome in N. gonorrhoeae-infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.Keywords: Neisseria gonorrhoeae, honokiol, NLRP3 inflammasome, mitochondria, bactericiide

Shih-Lung Cheng,1,2 Ming-Lin Ho,3 Yun-Fa Lai,4 Hao-Chien Wang,5 Jeng-Yuan Hsu,6 Shih-Feng Liu,7,8 Ming-Shyang Huang,9 Cheng-Hung Lee,10 Ching-Hsiung Lin,3,11 Liang-Wen Hang,12,13 Yu-Chih Liu,14 Kuang-Yao Yang,15,16,* Jia-Horng Wang14,17,* 1Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taoyuan, Taiwan; 3Division of Chest Medicine, Kuang Tien General Hospital, Taichung, Taiwan; 4Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 6Division of Clinical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 7Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 9Department of Internal Medicine, E-DA Cancer Hospital and Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 10Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 11Division of Chest Medicine, Changhua Christian Hospital, Changhua, Taiwan; 12School of Nursing & Graduate Institute of Nursing, China Medical University, Taichung, Taiwan; 13Sleep Medicine Center, China Medical University Hospital, Taichung, Taiwan; 14Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 15Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 16Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 17Hyperbaric Oxygen Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Kuang-Yao Yang; Jia-Horng Wang Tel +886-2-28757455Fax +886-2-28757610Email kyyang@vghtpe.gov.tw; jiahorng.wang@gmail.comIntroduction: In the prospective, observational, 16-week REACT study conducted between October 21, 2008 and May 12, 2011, we compared the real-world effectiveness of anti-inflammatory reliever and maintenance therapy with budesonide/formoterol (Symbicort® Turbuhaler) and maintenance therapy with fixed-dose fluticasone/salmeterol (Seretide®) plus as-needed, short-acting β2 agonists (SABAs) in Taiwanese patients with inadequate asthma control.Methods: Asthma control was assessed using the five-item Asthma Control Questionnaire (ACQ-5) and standardized pulmonary function testing. Assessments were performed at baseline and at weeks 4– 5 and 12– 16. Overall, we enrolled 842 patients at 11 clinics, 723 of whom were included in analyses (budesonide/formoterol, 563.3± 1.3 μg/d, n=551; fluticasone/salmeterol, 1013.8± 1.4 μg/d, n=172).Results: At baseline, 72.5% and 27.5% of all patients had “partly” and “uncontrolled” asthma, respectively. Mean±SD ACQ-5 scores were 1.54± 1.06 and 1.46± 1.28 in the budesonide/formoterol and fluticasone/salmeterol groups, respectively. ACQ-5 scores significantly improved from baseline (ie, decreased) in both groups at weeks 4 and 16. ACQ-5 difference scores were significantly lower in the budesonide/formoterol group (− 0.91± 1.11) than the fluticasone/salmeterol group (− 0.69± 1.27) at the end of the study (p=0.027). Peak expiratory flow rate significantly improved from baseline in the budesonide/formoterol but not the fluticasone/salmeterol group at the end of the study. Severe exacerbation rates and medical resource utilization were comparable between the budesonide/formoterol and fluticasone/salmeterol groups.Conclusion: Collectively, results indicate the real-world effectiveness of budesonide/formoterol anti-inflammatory reliever and maintenance therapy is better than fixed-dose fluticasone/salmeterol plus as-needed SABA.Trial Registration: ClinicalTrials.gov registration number: NCT00784953.Keywords: budesonide/formoterol, fluticasone propionate/salmeterol, anti-inflammatory reliever and maintenance, real-world

Cheng SL, Ho ML, Lai YF, et al. Drug Des Devel Ther. 2020;14:5441–5450.The authors have advised there is an error in the formatting of the paper title on page 5441, the title “Budesonide/Formoterol Anti-Inflammatory Reliever and Maintenance or Fluticasone Propionate/Salmeterol Plus As-Needed, Short-Acting β2 Agonist: Real-World Effectiveness in pAtients without Optimally Controlled asThma (REACT) Study” should read “Budesonide/Formoterol Anti-Inflammatory Reliever and Maintenance or Fluticasone Propionate/Salmeterol Plus As-Needed, Short-Acting β2 Agonist: Real-world Effectiveness in pAtients without optimally Controlled asThma (REACT) Study”.The authors have also advised the affiliation list on page 5441 is incorrect. Read the original article

Background: Previous studies suggest the association between early-life weight gain and asthma. It remains unclear whether early-life weight gain is associated with atopic or non-atopic asthma. This study aimed to investigate whether early-life weight gain is associated with atopic or non-atopic asthma. Methods: Included in this study were 1343 singleton-birth children (761 boys, 57%) born between January 2010 and December 2011 participating in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort were evaluated by a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and interviewed by pediatricians between July 1, 2016 and May 31, 2018 at the mean age of 6.4 years. Weight gain z-scores during the first 6, 12, and 18 months of life were classified into 4 groups: slow (below −0.67), on track (−0.67 to 0.67), rapid (0.67 to 1.28), and extremely rapid (above 1.28). The main outcomes were atopic and non-atopic asthma. Asthma was defined as having physician-diagnosed asthma and the presence of wheeze or asthma exacerbations in the last 12 months. Atopy was determined by Phadiatop Infant. Results: The extremely rapid weight gain group of children during the first 6, 12, and 18 months of life was significantly associated with an increased risk of non-atopic asthma (adjusted odd ratio [AOR], 2.14, 95% confidence interval [CI], 1.01–4.53 for the first 6 months; AOR, 2.86, 95% CI, 1.34–6.14 for the first 12 months; AOR, 3.26, 95% CI 1.49–7.15 for the first 18 months) compared with the on track group. No significant association was found in atopic asthma. A sex-stratified analysis revealed the association of early-life weight gain with non-atopic asthma was statistically significant only in boys (AOR, 4.24, 95% CI, 1.44–12.50). Conclusion: Extremely rapid weight gain during the first 6–18 months of life was significantly associated with 2.1- to 3.3-fold increased risk of non-atopic asthma, with a more pronounced risk found in boys.

Purpose: Yttrium-90 (90Y) radioembolization with an escalated dose has been shown to improve clinical outcomes compared with standard dose radioembolization, but there are few data on the local control of primary liver tumors. We reported the clinical outcomes of patients with unresectable primary liver tumors treated with 90Y radioembolization with an escalated dose. Methods and Materials: Clinical data of patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and biphenotypic tumors (cHCC-CC) treated with radioembolization with an escalated dose (≥150 Gy) between 2013 and 2020 with >3 months follow-up were retrospectively reviewed. The primary endpoint was freedom from local progression. Clinical response was defined by Modified Response Evaluation Criteria in Solid Tumours and toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. Results: Fifty-three patients with HCC and 15 patients with CC/cHCC-CC were analyzed. The median dose delivered was 205 Gy (interquartile range, 183-253 Gy) and 198 Gy (interquartile range, 154-234 Gy) for patients with HCC and CC/cHCC-CC, respectively. The 1-year freedom from local progression rate was 54% (95% confidence interval [CI], 38%-78%) for patients with HCC and 66% (95% CI, 42%-100%) for patients with CC/cHCC-CC. For patients with HCC, United Network for Organ Sharing nodal stage 1 (P = .01), nonsolitary tumors (P = .02), pretreatment α-fetoprotein of >7.7 ng/mL (P = .006), and ≤268 Gy dose delivered (P = .003) were predictors for local progression on multivariate Cox analysis. No patients with HCC who received a dose >268 Gy had a local tumor progression. The 1-year overall survival for patients with HCC was 74% (95% CI, 61%-89%). After radioembolization, 5 (7%) patients had grade 3 ascites, and 4 (6%) patients had grade 3/4 hyperbilirubinemia. Conclusions: Treatment of unresectable primary liver tumors with 90Y radioembolization with an escalated dose was safe and well tolerated. Delivery of >268 Gy may improve local tumor control of HCC. Determination of the maximum tolerated dose needs to be performed in the context of future prospective dose-escalation trials to further evaluate the safety and efficacy of such an approach.

Objectives: In this study, we propose a deep learning-based approach to predict Intensity-modulated radiation therapy (IMRT) quality assurance (QA) gamma passing rates using delivery fluence informed by log files. Methods: A total of 112 IMRT plans for chest cancers were planned and measured by portal dosimetry equipped on TrueBeam linac. The convolutional neural network (CNN) based learning model was trained using delivery fluence as inputs and gamma passing rates (GPRs) of 4 different criteria (3%/3 mm, 2%/3 mm, 3%/2 mm, and 2%/2 mm) as outputs. Model performance for both validation and test sets was assessed using mean absolute error (MAE), mean squared error (MSE), root MSE (RMSE), Spearman rank correlation coefficients (Sr), and Determination coefficient ( R 2 ) between the measured and predicted GPR values. Results: In the test set, the MAE of the prediction model were 0.402, 0.511, 1.724, and 2.530, the MSE were 0.640, 0.986, 6.654, and 9.508, the RMSE were 0.800, 0.993, 2.580, and 3.083, the Sr were 0.643, 0.684, 0.821, and 0.824 ( P

Purpose: To propose an improved stem cell-based strategy for limbal stem cell deficiency (LSCD) treatment. Design: Experimental randomized or parallel-group animal study. Subjects: Fifty adult male New Zealand white rabbits. Methods: Human limbal stem/progenitor cells (LSCs) and limbal stromal stem/progenitor cells (LSSCs) were cultured in serum-free conditions and further differentiated into corneal epithelial cells and keratocytes, respectively. All cell types were characterized with lineage-specific markers. Gene expression analysis was performed to identify the potential function of LSSCs in corneal regeneration. Two LSCD models of rabbits for transplantations were used: transplantation performed at the time of limbal and corneal epithelial excision (LSCD model) and transplantation performed after clinical signs were induced in an LSCD model (pLSCD model). The pLSCD model better mimics the pathologic changes and symptoms of human LSCD. Rabbit models received LSC or LSC plus LSSC treatment. Corneal epithelial defects, neovascularization, and opacity were assessed every 3 weeks for 24 weeks. ZsGreen-labeled LSSCs were used for short-term tracking in vivo. Main Outcome Measures: Rates of corneal epithelial defect area, corneal neovascularization and opacity scores, graft survival rate, and immunofluorescence staining of specific markers. Results: Both LSC transplantation and LSC plus LSSC cotransplantation effectively repaired the corneal surface in the LSCD model. These 2 strategies showed no significant differences in terms of graft survival rate or epithelial repair. However, corneal opacity was observed in the LSC group (in 3 of 8 rabbits), but not in the LSC plus LSSC group. Notably, when treating LSCD rabbits with distinguishable stromal opacification and neovascularization, cotransplantation of LSCs and LSSCs exhibited significantly better therapeutic effects than transplantation of LSCs alone, with graft survival rates of 87.5% and 37.5%, respectively. The implanted LSSCs could differentiate into keratocytes during the wound-healing process. RNA sequencing analysis showed that the stromal cells produced not only a collagen-rich extracellular matrix to facilitate reconstruction of the lamellar structure, but also niche factors that accelerated epithelial cell growth and inhibited angiogenesis and inflammation. Conclusions: These findings highlight the support of stromal cells in niche homeostasis and tissue regeneration, providing LSC plus LSSC cotransplantation as a new treatment strategy for corneal blindness.

Patients with persistent sciatic artery are at high risk for development of limb ischemia, aneurysm formation, and embolism. In this report, we identify a nonclassified left leg persistent sciatic artery in a patient with chronic limb ischemia. Vascular reconstruction was carried out by common iliac-deep femoral artery bypass to restore adequate arterial flow. Our approach to placement of the distal anastomosis on the deep femoral artery instead of on the popliteal artery, which is used in routine practice, may potentially increase treatment efficacy and decrease surgical complications. At 2-year follow-up, the patient remained asymptomatic and in good health. Keywords: Persistent sciatic artery (PSA), Bypass, Patency

Background: Magnetic resonance (MR) black-blood thrombus imaging (BTI) is an accurate diagnostic technique for detecting deep vein thrombosis (DVT) but to date there have been no studies comparing the diagnostic performance and consistency of this technique at different field strengths. In this study, we evaluated and compared the diagnostic performance of BTI for detecting DVT at 1.5 T and 3.0 T field strengths. Methods: A total of 40 patients with DVT were enrolled in this study from November 2015 up to October 2018. All patients underwent BTI, a contrast-free T1-weighted MR imaging technique for detecting DVT, and contrast-enhanced MR venography (CE-MRV) at 1.5 T or 3.0 T field strengths. The MR data analyses used 1160 segments from the venous lumen of the 40 patients. The signal-to-noise ratio and contrast-to-noise ratio between thrombus and muscle/lumen were calculated to compare BTI at 1.5 T or 3.0 T to determine the image performance for thrombus detection at 1.5 T or 3.0 T. Two physicians blinded to the study evaluated all BTI images and calculated the overall sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV), accuracy, and diagnostic consistency at 1.5 T and 3.0 T. These images and values were compared to control CE-MRV images that had been obtained by 2 senior physicians and used as reference standards. In addition, the reliability and consistency of diagnoses between observers were also evaluated. Results: Two study-blind physicians reviewed all BTI images to diagnose thrombus and to determine SE, SP, PPV, NPV, and accuracy. There were no statistical differences in SE, SP, PPV, NPV, or accuracy between the 1.5 T and 3.0 T groups. Conclusions: Black-blood thrombus imaging has high SE, SP, and accuracy for DVT diagnosis both at 1.5 T and 3.0 T field strengths. This noninvasive diagnostic technique, which does not require the use of contrast agents, can be widely used in the clinical screening of DVT and follow-up after treatment.

Background: Ovarian cancer is the seventh most commonly diagnosed malignancy worldwide and has the highest mortality rate among all gynecological cancers. Chinese herbal medicine (CHM) is widely applied in Taiwan and has been used in integrated therapies to treat patients with cancer. Methods: Patients with ovarian cancer who were registered in the Taiwan Registry for Catastrophic Illness Patients Database between 1997 and 2012 were considered for this study. A 1:1 individual matching by age was implemented. A total of 101 CHM users and 101 non-CHM users were involved. A Cox proportional hazard regression model was applied to evaluate the hazard ratio of overall mortality. The Kaplan-Meier method and log-rank test were used to calculate the cumulative incidence of the overall survival rate. Association rule mining and network analysis were used to analyze CHM prescription patterns. Results: CHM users showed a significantly lower risk of overall mortality than nonusers (hazard ratio = 0.45, 95% confidence interval = 0.23-0.91; P = .0256; multivariate Cox proportional hazard model). The cumulative incidence of the overall survival probability was higher for CHM users than for non-CHM users (log-rank test, P = .0009). Association rule mining and network analysis suggested that the main CHM cluster was associated with the usage of Bu-Zhong-Yi-Qi-Tang, Chuan-Xiong, and Xi-Xin, followed by the use of Bai-Shao, Da-Huang, and Di-Huang. Conclusions: CHM, as an adjunctive therapy, may reduce the overall mortality in patients with ovarian cancer. A list of herbal medicines that could potentially be used in future studies and clinical trials has also been provided.

Background: There are no publicly available tools designed specifically to assist policy makers to make informed decisions about the optimal ages of breast cancer screening initiation for different populations of US women. Objective: To use three established simulation models to develop a web-based tool called Mammo OUTPuT. Methods: The simulation models use the 1970 US birth cohort and common parameters for incidence, digital screening performance, and treatment effects. Outcomes include breast cancers diagnosed, breast cancer deaths averted, breast cancer mortality reduction, false-positive mammograms, benign biopsies, and overdiagnosis. The Mammo OUTPuT tool displays these outcomes for combinations of age at screening initiation (every year from 40 to 49), annual versus biennial interval, lifetime versus 10-year horizon, and breast density, compared to waiting to start biennial screening at age 50 and continuing to 74. The tool was piloted by decision makers (n = 16) who completed surveys. Results: The tool demonstrates that benefits in the 40s increase linearly with earlier initiation age, without a specific threshold age. Likewise, the harms of screening increase monotonically with earlier ages of initiation in the 40s. The tool also shows users how the balance of benefits and harms varies with breast density. Surveys revealed that 100% of users (16/16) liked the appearance of the site; 94% (15/16) found the tool helpful; and 94% (15/16) would recommend the tool to a colleague. Conclusions: This tool synthesizes a representative subset of the most current CISNET (Cancer Intervention and Surveillance Modeling Network) simulation model outcomes to provide policy makers with quantitative data on the benefits and harms of screening women in the 40s. Ultimate decisions will depend on program goals, the population served, and informed judgments about the weight of benefits and harms.

Background: Protease-activated receptor-2 (PAR-2)-modulated tight junctions (TJs) have been suggested to be involved in the pathogenesis of chronic inflammatory diseases. However, immunopathogenesis remains to be investigated among patients with allergic rhinitis (AR). Objective: This study sought to investigate the role of PAR-2 in the modulation of epithelial barrier function and the expression of TJs in the nasal mucosa of AR patients. Methods: The expression of TJs and PAR-2 of the nasal mucosa in AR patients and control subjects by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. In vitro, Primary human nasal epithelial cells (pHNECs) of AR patients were stimulated by Der p1 to analyze the correlation between PAR-2 and TJs expression. Der p1-induced pHNECs were treated with the PAR-2 agonist SLIGRL-NH2 and antagonist FSLLRY-NH2. Fluorescein isothiocyanate–dextran 4 kDa detection was employed as an indicator of epithelial permeability. Results: Lower expression levels of TJs in the nasal epithelium of AR patients were observed in comparison with that in control subjects. The PAR-2 level was markedly increased following treatment with 1,000 ng/mL of Der p1 for 24 hours in a cellular model of AR. The expression of PAR-2 was increased in Der p1-induced pHNECs of AR patients and correlated inversely with zonula occlidens (ZO)-1 and claudin-1. Treatment with Der p1 further downregulated TJs expression and promoted an increased epithelial permeability in Der p1-induced pHNECs. Conclusions: PAR-2 could downregulate the expression of ZO-1 and claudin-1, which is involved in epithelial barrier dysfunction in AR. [ABSTRACT FROM AUTHOR]

Objectives: To describe the technique, efficacy, and safety of transvenous embolisation (TVE) of cavernous sinus arteriovenous fistulas (CSDAVFs) via the inferior petrosal sinus (IPS) with detachable coils and acrylic glue.Methods: Spontaneous unilateral CSDAVFs were confirmed by cerebral angiography in eight patients, with angiographic patency of the ipsilateral IPS in three and angiographic non-visualisation of the ipsilateral IPS in five. There were two patients with complete occlusion of the ipsilateral internal jugular vein (IJV). TVE with detachable coils and acrylic glue were performed through a femoral vein and an IPS approach.Results: TVE viaipsilateral IPS was successfully performed in all eight patients in our group. The number of detachable coils for each patient ranged from 2 to 8 (mean, 5.0). Angiography immediately after TVE showed complete occlusion of the CSCAVFs in seven patients and nearly complete occlusion in one. Complete recovery of clinical symptoms was achieved in all eight patients. No recurrence of clinical symptoms was observed at follow-up.Conclusions: Transvenous embolisation via an IPS approach is a highly efficient and safe treatment for CSDAVFs. Embolisation with a combination of coils and acrylic glue may help to achieve complete occlusion of fistulas with fewer coils. [ABSTRACT FROM AUTHOR]

Rationale: Asthma is often work-related and can be classified as atopic or nonatopic on the basis of its pathogenesis. Few studies have reported an association between exposure to occupational asthmogens and asthma with and without atopy. Objectives: We investigated, in adults with asthma, whether occupational exposure to asthmogens influenced the risk of having atopic or nonatopic asthma, and their level of lung function. Methods: We recruited 504 hospital-based adults with current asthma, 504 community-based control subjects, and 504 hospital-based control subjects in southern Taiwan. Asthma with atopy was defined as having asthma in combination with an increase in total IgE (>=100 U/ml) or a positive Phadiatop test (>=0.35 Pharmacia arbitrary unit/L) (Pharmacia ImmunoCAP; Pharmacia, Uppsala, Sweden). Occupational exposure to asthmogens was assessed with an asthma-specific job exposure matrix. Measurements and Main Results: We found a significant association between atopic asthma and exposure to high molecular weight asthmogens (adjusted odds ratio [AOR], 4.0; 95% confidence interval [CI], 1.8-8.9). Nonatopic asthma was significantly associated with exposure to low molecular weight asthmogens (AOR, 2.6; 95% CI, 1.6-4.3), including industrial cleaning agents and metal sensitizers. Agriculture was associated with both atopic and nonatopic asthma (AOR, 7.8; 95% CI, 2.8-21.8; and AOR, 4.1; 95% CI, 1.3-13.0, respectively). The ratio of FEV(1) to FVC in the high-risk group was significantly lower than in the no-risk group (P = 0.026) in currently employed patients with asthma. Conclusions: In adults with asthma, occupational exposure to high and low molecular weight asthmogens appears to produce differential risks for atopic and nonatopic asthma. [ABSTRACT FROM AUTHOR]

Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non-small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC(50) value was observed in TSL-1-treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dose-dependent manner. Thus, the TSL-1-induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: O(6)-methylguanine-DNA methyltransferase (MGMT) ameliorates mutagenic, carcinogenic, and cytotoxic adducts from O(6)-methylguanine in DNA through a direct reversal mechanism. Decreased expression of MGMT has been reported in a variety of human malignant tumors. The purpose of this study was to clarify the correlation of MGMT expression levels in oral squamous cell carcinoma (OSCC) with promoter hypermethylation and with betel quid chewing and cigarette smoking. STUDY DESIGN: MGMT protein expression in 63 cases of oral squamous cell carcinoma by immunohistochemistry was investigated. Methylation status of the MGMT was analyzed by methylation-specific PCR. Correlation with clinicopathologic parameters was then tested by statistical analysis. RESULTS: MGMT immunohistochemistry revealed nuclear staining in normal epithelium, whereas 47 (75%) of 63 OSCC tumors were devoid of MGMT expression and this was related to tumor cell differentiation. Furthermore, the association between loss of MGMT expression and promoter hypermethylation was significant. Lacking protein expression for MGMT in OSCC was also associated with the use of betel quid. CONCLUSIONS: The results suggest that the absence of MGMT expression, which would seem to be associated with promoter hypermethylation, is related to betel quid chewing and, thus, in turn, might be a significant event in oral carcinogenesis. [ABSTRACT FROM AUTHOR]