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Patient Characteristics, Safety, and Tolerability With Telaprevir Treatment for HCV in the Clinic:a Retrospective, Multicenter Study

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journal of Clinical and Translational Hepatology 2014年第2期2卷 65-73页

作者： Steven L. Flamm Paul j. Pockros leif Bengtsson Mark Friedman Northwestern University Feinberg School of Medicine Chicago Illinois USA Scripps Clinic and Scripps Translational Science Institute La Jolla California USA Vertex Pharmaceuticals Incorporated Boston Massachusetts USA

Background and Aims: There is a paucity of information regarding similarities and differences between patients from the phase 3 studies of telaprevir and those receiving telaprevir in clinical practice. Methods: This retrospective chart review evaluated baseline characteristics and follow-up safety and tolerability data for patients with hepatitis C virus (HCV) infection treated with telaprevir and peginterferon alfa and ribavirin (PR) in clinical practice. Results: In total, 338 charts from patients at four academic and three community US treatment centers who received telaprevir and PR and had at least 12 weeks of follow-up data were included;62%were from academic centers and 38% were from community centers. Of the 338 patients, 269 completed 12 weeks of telaprevir and PR;32 discontinued due to adverse events. Mean age was 55 years;patients were predominantly white (79.3%) males (58.9%) with genotype 1a HCV infection (61.8%);35.5%were reported to have cirrhosis at baseline;and 55.3%previously received PR. Hypertension and depres-sion were the most common comorbidities. Patient charac-teristics outside the per-protocol minimum criteria used in the phase 3 studies of telaprevir were, e.g., hemoglobin, 9.2%;albumin, 5.3%;platelets, 11.5%;and neutrophil count, 5.6%. Adverse events occurred in 329/338 (97.3%) patients, with anemia, fatigue, nausea, and rash being the most common. Of 38 hospitalizations, 26 were deemed related to telaprevir and PR. Three patients died due to pneumonia, septic shock, and hepatorenal syndrome (n=1 each). Conclusions: These findings complement those reported from rigorous, randomized controlled studies with telaprevir-based treatment and provide a general assess-ment of similarities and/or differences between patients from the phase 3 studies of telaprevir and those treated with telaprevir in clinical practice.

关键词： Hepatitis C virus Combination drug therapy Protease inhibitors Liver diseases

Eosinophil associated genes in the inflammatory bowel disease 4 region:Correlation to inflammatory bowel disease revealed

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World journal of Gastroenterology 2012年第44期18卷 6409-6419页

作者： Kristin Blom jenny Rubin jonas Halfvarson leif Trkvist Anders Rnnblom Per Sangfelt Mikael Lrdal Ulla-Britt jnsson Urban Sjqvist Lena Douhan Hkansson Per Venge Marie Carlson Department of Medical Sciences Clinical ChemistryUppsala University HospitalSE-75185 UppsalaSweden Division of Gastroenterology Department of Intestinal Medicinerebro University HospitalSE-70185 rebroSweden School of Health and Medical Sciences rebro UniversitySE-70185 rebroSweden IBD Clinical research group Karolinska University HospitalSE-17177 StockholmSweden Department for Clinical Science Intervention and TechnologyKarolinska University HospitalSE-17177 StockholmSweden Department of Medical Sciences Gastroenterology Research GroupUppsala UniversitySE-75185 UppsalaSweden Department of Medicine Karolinska InstitutetSE-17177 StockholmSweden

AIM： To study the association between inflammatory bowel disease （IBD） and genetic variations in eosinophil protein X （EPX） and eosinophil cationic protein （ECP）. METHODS： DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn＇s disease （CD）, 592 with ulcerative colitis （UC） and 300 healthy subjects. The EPX405 （G 〉 C, rs2013109）, ECP434 （G 〉 C, rs2073342） and ECP562 （G 〉 C, rs2233860） gene polymorphisms were analysed, by the 5＇-nuclease allelic discrimination assay. For de- termination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylam- monium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent as- say. The intracellular content of ECP was analysed with the UniCAP system as described by the manufacturer. Statistical tests for calculations of results were χ2 test, Fisher＇s exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P 〈 0.05 were considered statistically ***： The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years （n = 57） was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject＇s genotype frequencies of ECP434 （GG = 57%, GC = 38%, CC = 5%; P = 0.010） and ECP562 （GG = 68%, GC = 29%,CC = 3%; P = 0.009）. The genotype frequencies for females, with an age of dis- ease onset of ≥ 45 years with CD （n = 62）, was for the ECP434 and ECP562 genotypes GG = 37%, GC =52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 （P = 0.010） and ECP562 （P = 0.013）. The intracellular protein concen- tration of EPX and ECP was calculated in μg/10^6 eosi- nophils and then correlated to the EPX 405 genotypes

关键词： Eosinophil derived neurotoxin RNase 2 RNase 3 Single nucleotide polymorphism Inflamma-tion bowel disease Crohn's disease Ulcerative colitis

Mucosal-associated invariant T cells and oral microbiome in persistent apical periodontitis

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International journal of Oral Science 2019年第2期11卷 131-142页

作者： Haleh Davanian Rogier Aaron Gaiser Mikael Silfverberg Luisa W. Hugerth Michal j. Sobkowiak Liyan Lu Katie Healy johan K. Sandberg Peggy Nasman jorgen Karlsson leif jansson Lars Engstrand Margaret Sallberg Chen Department of Dental Medicine Karolinska InstitutetHuddingeSweden Department of Microbiology Tumor and Cell Biology and Science for Life LaboratoryKarolinska InstitutetStockholmSweden Clinical Genomics Facility Science for Life LaboratorySolnaSweden Department of Medicine Karolinska InstitutetHuddingeSweden Clinic of Endodontics and Periodontology Eastman Institute StockholmStockholmSweden

Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic ***-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal *** was recently shown that MAIT cells are present in the oral mucosal tissue,but the involvement of MAIT cells in AP is ***,comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-jα33,Vα7.2- jα20,Vα7.2-jα12,Cα and tumour necrosis factor (TNF),interferon (IFN)-γ and interleukin (IL)-17A transcripts,resembling a MAIT cell ***,in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4^+ *** gingival tissues,the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial *** merged in an integrated view,the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-jα33,Cα,and IL-17A transcript expressions in AP,implying that MAIT cells could play a role in the local defence at the oral tissue *** conclusion,we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take *** findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.

关键词： apical periodontitis(AP) Mucosal-associated invariant T(MAIT) AP

Enzymatic Method for Rapid Determination of Oxalic Acid in Bleaching Filtrates from the Pulp and Paper Industry

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journal of Donghua University(English Edition) 2005年第5期22卷 64-68页

作者：洪枫 Sj(O|¨)DE Anders NILVEBRANT Nils-Olof j(O|¨)NSSON leif j Institute of Biological Sciences and Biotechnology Donghua University Shanghai 200051 Division for ChemistryKarlstad UniversitySE-65188 KarlstadSweden Division for Chemistry Karlstad University SE-65188 KarlstadSweden STFI-Pack forsk ABSwedish Pulp and Paper Research InstituteSE-11486 StockholmSweden STFI-Pack forsk AB Swedish Pulp and Paper Research Institute SE-11486 StockholmSweden Division for Chemistry Karlstad University SE-65188 KarlstadSweden

Bleaching with oxygen-containing agents and recirculation of process streams in the pulp and paper industry has increased the accumulation of oxalic acid and danger for precipitation of calcium oxalate encrusts, scaling. Analysis and control of oxalic acid in bleaching filtrates is therefore becoming increasingly important in the pulp and paper industry. Chromatographic methods, such as IC and HPLC, are generally more time-consuming but are valuable as standard methods for determination of oxalic acid. However, the instrumentation needed is expensive and stationary. In this study, an enzymatic method based on oxalate oxidase and peroxidase was developed to determine oxalic acid in authentic bleaching filtrates using a spectrophotometer. The results showed that bleaching filtrates contain some compounds interfering with the enzymatic method. Pretreatment of the samples with activated charcoal was a successful approach for decreasing problems with interference. By using dilution followed by charcoal treatment, the results obtained from five bleaching filtrates with the colorimetric method correlated very well with those obtained using IC. This study offers a selective, fast and mobile analysis method to determine oxalic acid in bleaching fiRrates from the pulp and paper industry, The convenient enzyme-based method improves the possibilities for control of critical oxalic acid concentrations in closed-loop bleaching streams.

关键词： oxalic acid oxalate oxidase colorimetric method bleaching filtrates activated charcoal the pulp and paper industry

Distribution of Mercury in a Gadoid Fish Species, Tusk （Brosme brosme）, and Its Implication for Food Safety

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journal of Food Science and Engineering 2012年第11期2卷 603-615页

作者： Kristine Kvangarsnes Sylvia Frantzen Kare julshamn leif j. Saethret Kjell Nedreaas Amund Maage National Institute of Nutrition and Seafood Research P.O. Box Bergen 5817 Norway Department of Chemistry University of Bergen Alleg Bergen 5007 Norway Institute of Marine Research Postboks 1870 Nordnes Bergen 5007 Bergen

The tusk （Brosme brosme） is a popular gadoid fish for human consumption, which also is susceptible to mercury accumulation. However, few data of mercury levels in tusk exist, and it is difficult to compare tusk fished from assumed contaminated areas with background levels. The aim of this study was to increase the information of mercury levels observed in tusk from the Northeast Atlantic Ocean. Samples of tusk were collected from seven different localities in open ocean areas, nine along the Norwegian coastal current （NCC）, and from two fjord stations. Determinations of mercury in muscle and liver were carried out using inductive coupled plasma mass spectrometry （ICPMS） after microwave-assisted wet digestion. The highest concentrations of mercury in muscle were found in tusk captured from the fjords Hardangerfjord and Sorfjord, and had mean concentrations of mercury at 1.5 and 1.7 mg kg＂~ wet weight （ww）, respectively, where all of the tusk exceeded EU＇s upper limit of 0.5 mg kg1 ww. The lowest concentrations of mercury were observed in tusk captured from the open ocean areas, and the concentrations ranged from 0.08 to 0.30 mg kg-1 ww. Mercury concentrations of tusk captured along the NCC ranged from 0.21 to 0.49 mg kg-1 ww. Mercury concentrations increased with the weight of the tusk, and variance analysis （ANOVA） of weight normalized mercury concentrations showed that there were significant differences in mercury concentrations between tusk collected from the open ocean, NCC and fjords, which indicates that differences in mercury concentration between different areas arecaused by other factors.

关键词： Tusk mercury food safety U-864 ICPMS.

Worsening Clinical Outcome with Increasing Number of So-Called Off-Label or Unapproved Indications for Use of Drug Eluting Stents

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World journal of Cardiovascular Diseases 2016年第7期6卷 224-234页

作者： Anders M. Galløe Ulrik Abildgaard Henning Kelbæk Niels Bligaard jørgen L. jeppesen leif Thuesen Peter R. Hansen Department of Cardiology Zealand University Hospital Roskilde Denmark Department of Cardiology Copenhagen University Hospital Gentofte Denmark Department of Cardiology Copenhagen University Hospital Bispebjerg Denmark Department of Medicine Copenhagen University Hospital Glostrup Denmark Department of Cardiology Aalborg University Hospital Aalborg Denmark

Objective: We explored the impact of increasing number of off-label patient and lesion character-istics on 5-year clinical outcome following implantation of first generation drug eluting stents. Furthermore we tried to assess if stent performance might be improved if the off-label character-istics present were taken into account to guide the stent brand selection. Design: A total of 2888 coronary lesions treated with first generation drug eluting stents were classified for eventual presence of 18 different off-label characteristics and correlated to the 5-year clinical outcome by multiple stepwise Cox regression analysis. Results: The composite of cardiac death, myocardial infarction and target vessel revascularization (major adverse cardiac event, MACE) was 16.7% in cases with zero off-label characteristics and showed a stepwise increased rate up to 32.7% in cases with 5 off-label characteristics. The MACE rate for the sirolimus eluting stent appears to be 10% lower than the paclitaxel stent group and it may be further reduced by 10% - 18% if the off-label characteristics present in each case were taken into account to guide the stent brand selection. Conclusion: With increasing number of concomitantly appearing off-label characteristics there is a stepwise increase in MACE rate. The MACE rate may be reduced if the off-label characteristics were used to guide the stent brand selection.

关键词： Drug Eluting Stents

受多氯联苯污染的jrnsjn湖治理前后野生鲈鱼的生理与形态学研究

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人类环境杂志 1998年第5期27卷 418-424页

作者： Lars Frlin leif Norrgren 聂晶磊 Department Swedish

jarnsjon湖位于瑞典南部的埃姆河支流,过去受到造纸厂含多氯联苯(PCB)污水的污染。本文应用生理学和形态学方法研究了被PCB污染的底泥清除前与清除后鲈鱼(Perca fluviatilis)的健康状况。在整治前,以形态学为特征,通过鳃和肝损伤的生物... 详细信息

jarnsjon湖位于瑞典南部的埃姆河支流,过去受到造纸厂含多氯联苯(PCB)污水的污染。本文应用生理学和形态学方法研究了被PCB污染的底泥清除前与清除后鲈鱼(Perca fluviatilis)的健康状况。在整治前,以形态学为特征,通过鳃和肝损伤的生物化学和生理学效应研究了PCB污染的jarnsjon湖中鲈鱼。发现了一个预料之外的非响应性系统——鲈鱼肝的EROD-CYPlA系统。这个结果似乎表明,仅有PCB的污染并不能解释这个观察结果。在清除PCB活动2年以后,鲈鱼又健康地生活在jarnsjon湖中。但是,一些来自埃姆河下游地区的雌性鲈鱼表现出严重的性腺不正常。这个结果可能表明,jarnsjon湖中的这些鲈鱼除整治理活动之外,还受到其它因素的影响。

关键词：多氯联苯野生钙鱼生理形态学湖泊污染污染治理比较分析

Fungal diversity notes 709–839: taxonomic and phylogenetic contributions to fungal taxa with an emphasis on fungi on Rosaceae

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Fungal Diversity 2018年第2期89卷 1-236页

作者： Dhanushka N.Wanasinghe Chayanard Phukhamsakda Kevin D.Hyde Rajesh jeewon Hyang Burm Lee E.B.Gareth jones Saowaluck Tibpromma Danushka S.Tennakoon Asha j.Dissanayake Subashini C.jayasiri Yusufjon Gafforov Erio Camporesi Timur SBulgakov Anusha HEkanayake Rekhani Hansika Perera Milan CSamarakoon Ishani DGoonasekara Ausana Mapook Wen-jing Li Indunil CSenanayake junfu Li Chada Norphanphoun Mingkwan Doilom Ali H Bahkali jianchu Xu Peter EMortimer leif Tibell Sanja Tibell Samantha C.Karunarathna Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of ScienceKunming 650201YunnanPeople’s Republic of China Center of Excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand World Agroforestry Centre East and Central AsiaKunming 650201YunnanPeople’s Republic of China Mushroom Research Foundation 128 M.3 Ban Pa Deng T.Pa PaeA.Mae TaengChiang Mai 50150Thailand Department of Health Sciences Faculty of ScienceUniversity of MauritiusReduitMauritius Environmental Microbiology Lab Division of Food TechnologyBiotechnology&AgrochemistryCollege of Agriculture and Life SciencesChonnam National UniversityYongbong-Dong 300Buk-GuGwangju 61186Korea Nantgaredig 33 B St.Edwards Road Southsea HantsHampshire PO53DHUK Institute of Plant and Environment Protection Beijing Academy of Agriculture and Forestry SciencesBeijing 100097People’s Republic of China Laboratory of Mycology Institute of BotanyAcademy of Sciences of the Republic of Uzbekistan32 Durmon Yuli StreetTashkentUzbekistan 100125 A.M.B.Gruppo Micologico Forlivese"Antonio Cicognani"Via Roma 18Forlı`Italy A.M.B Circolo Micologico"Giovanni Carini"C.P.314 BresciaItaly Societa`per gli Studi Naturalistici della Romagna C.P.144 BagnacavalloRAItaly Russian Research Institute of Floriculture and Subtropical Crops 2/28 Yana Fabritsiusa StreetSochiKrasnodar RegionRussia 354002 Department of Biology Faculty of ScienceChiang Mai UniversityChiang Mai 50200Thailand Engineering Research Center of Southwest BioPharmaceutical Resources Ministry of EducationGuizhou UniversityGuiyang 550025GuizhouPeople’s Republic of China Department of Botany and Microbiology College of ScienceKing Saud UniversityP.O.Box:2455Riyadh 1145Saudi Arabia Department of Plant Medicine National Chiayi University300 Syuefu RoadChiayi City 60004Taiwan Department of Ecology University of KasselHeinrich-PlettStrasse4034132 KasselGermany Department of Organismal Biology Uppsala Univer

This paper is the seventh in the Fungal Diversity Notes series,where 131 taxa accommodated in 28 families are mainly described from Rosa(Rosaceae)and a few other *** fungal taxa are described in the present study,including 17 new genera,93 new species,four combinations,a sexual record for a species and new host records for 16 ***,Cycasicola,Dactylidina,Embarria,Hawksworthiana,Italica,Melanocucurbitaria,Melanodiplodia,Monoseptella,Uzbekistanica,Neoconiothyrium,Neopaucispora,Pararoussoella,Paraxylaria,Marjia,Sporormurispora and Xenomassariosphaeria are introduced as new ascomycete *** also introduce the new species Absidia jindoensis,Alternaria doliconidium,***,Angustimassarina rosarum,Astragalicola vasilyevae,Backusella locustae,Bartalinia rosicola,Bhatiellae rosae,Broomella rosae,Castanediella camelliae,Coelodictyosporium rosarum,Comoclathris rosae,***,Comoclathris rosigena,Coniochaeta baysunika,***,Cycasicola goaensis,Dactylidina shoemakeri,Dematiopleospora donetzica,***,***,Diaporthe rosae,***,Endoconidioma rosaehissaricae,Epicoccum rosae,Hawksworthiana clematidicola,***,Italica achilleae,Keissleriella phragmiticola,***,***,***,Lophiostoma rosae,Marjia tianschanica,***,Melanocucurbitaria uzbekistanica,Melanodiplodia tianschanica,Monoseptella rosae,Mucor fluvius,Muriformistrickeria rosae,Murilentithecium rosae,Neoascochyta rosicola,Neoconiothyrium rosae,Neopaucispora rosaecae,Neosetophoma rosarum,***,***,Neostagonospora artemisiae,Ophiobolus artemisiicola,Paraconiothyrium rosae,Paraphaeosphaeria rosae,***,Pararoussoella rosarum,Parathyridaria rosae,Paraxylaria rosacearum,Penicillium acidum,***,Phragmocamarosporium rosae,Pleospora rosae,***-caninae,Poaceicola agrostina,***,***,Populocrescentia ammophilae,***,Pseudocamarosporium pteleae,***-minoris,Pseudocercospora rosae,Pseudopithomyces rosae,Pseudost

关键词： Ascomycota Dothideomycetes Eurotiomycetes Italy Lecanoromycetes Mucoromycetes Phylogeny Rosa Rosaceae Russia Sordariomycetes Taxonomy UK Uzbekistan

血管紧张素转换酶抑制剂与非心脏手术后呼吸系统并发症或死亡率无关

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麻醉与镇痛 2013年第5期9卷 31-42页

作者： Alparslan Turan, MD jing You, MS Ayako Shiba, MD Andrea Kurz, MD leif Saager, MD Daniel I. Sessler, MD 张李娜(译) 桂波(译) 钱燕宁(校) Department of Outcomes Research Department of QuantitativeHealth Sciences Cleveland Clinic Cleveland Ohio 不详

背景通常血管紧张素转换酶抑制剂（***，ACEIs）的使用可致诸如咳嗽、血管神经性水肿、支气管痉挛等上呼吸道并发症；此外，术前ACEIs的使用与并发症发病率或死亡率增加有关。因此本研究我们的主要目标是评估成人非心脏手术患者围术期... 详细信息

背景通常血管紧张素转换酶抑制剂（***，ACEIs）的使用可致诸如咳嗽、血管神经性水肿、支气管痉挛等上呼吸道并发症；此外，术前ACEIs的使用与并发症发病率或死亡率增加有关。因此本研究我们的主要目标是评估成人非心脏手术患者围术期呼吸并发症发病率与ACEI治疗之间的关系，次要目标是评估术前使用ACEI和30天内死亡率之间的关系，以及住院期间接受全身麻醉的成人非心脏手术患者的并发症发病率和死亡率这一综合预后。方法我们评估了2005年至2009年之间在克利夫兰医学中心行非心脏手术的79228例患者[9905例（13％）ACEI使用者，66620例（87％）非ACEI使用者]。成功地将9028例ACEI使用者（占9905例患者的91％）和9028例对照者进行倾向配对。将配对的术中ACEI使用者和非ACEI使用者在术中和术后呼吸系统的总发病率、个别并发症、30天死亡率和住院期间的并发症综合发病率和死亡率进行比较。结果ACEI的术中[OR：1．09（97．5％CI：0．91，1．31），ACEI使用者相对于非ACEI使用者；P=0．28]或者术后[OR：0．97（97．5％CI：0．81，1．16），ACEI使用者相对于非ACEI使用者；P=0．69]使用与呼吸系统并发症综合发病率之间的关系无统计学意义。在倾向配对子集内，ACEI的使用与30天死亡率[OR：0．93（95％CI：0．73，1．19），ACEI组对非ACEI组；P=0．56]或住院期间并发症综合发生率和死亡率[OR：1．06（95％CI：0．97，1．15），ACEI组对非ACEI组；P=0．22]都没有关系。我们还观察到ACEI使用组和非ACEI使用组在术中多时段呈现的血流动力学特点、血管升压药的应用和胶体及晶体液的输入量等结果是相似的（标准差〈0．03）。结论我们没有发现ACEIs的使用与术中或术后上呼吸道并发症之间有任何联系。而且ACEIs的使用与住院期间并发症发病率及30天内死亡率也没有关系。

关键词：血管紧张素转换酶抑制剂呼吸系统并发症非心脏手术后死亡率非心脏手术患者呼吸道并发症 ACEI 总发病率