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Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon:cross-sectional study

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Infectious Diseases of Poverty 2017年第1期6卷 1205-1214页

作者： Tobias O.Apinjoh Regina N.Mugri Olivo Miotto Hanesh F.Chi Rolland B.Tata Judith K.Anchang-Kimbi Eleanor M.Fon Delphine A.Tangoh Robert V.Nyingchu Christopher Jacob Roberto Amato Abdoulaye Djimde Dominic Kwiatkowski Eric A.Achidi alfred Amambua-Ngwa Department of Biochemistry and Molecular Biology University of BueaBueaCameroon Department of Microbiology and Parasitology University of BueaBueaCameroon Mahidol-Oxford research Unit Faculty of Tropical MedicineMahidol UniversityBangkokThailand Department of Zoology and Animal Physiology University of BueaBueaCameroon Department of medical Laboratory Science University of BueaBueaCameroon Wellcome Trust Sanger institute HinxtonCambridge CB101SAUK Malaria research and Training Centre BamakoMali MRC Unit FajaraThe Gambia

Background:Drug resistance is one of the greatest challenges of malaria control programmes,with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy(ACT)partner drugs critical to elimination *** of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern ***:Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through crosssectional surveys from May 2013 to March 2014 along the slope of mount *** falciparum malaria parasitaemic blood,screened by light microscopy,was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq ***:A total of 259 participants were enrolled in this study from three different *** some alleles associated with drug resistance in pfdhfr,pfmdr1 and pfcrt were highly prevalent,less than 3%of all samples carried mutations in the pfkelch13 gene,none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast *** most prevalent haplotypes were triple mutants PfdhfrI51R59N108I164(99%),pfcrt-C72V73I74E75T76(47.3%),and single mutants PfdhpsS_(436)G_(437)K_(540)A_(581)A_(613)(69%)and Pfmdr1 N_(86)F)(184)D_(1246)(53.2%).Conclusions:The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon.

关键词： Molecular markers Drug resistance Plasmodium falciparum

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Pros and Cons in Therapeutic Evaluation of Paraoxonase 1 in Nerve Agent Toxicity

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Journal of Life Sciences 2013年第9期7卷 935-940页

作者： Manojkumar Valiyaveettil Yonas Alamneh Bhupendra P. Doctor alfred M. Sciuto Madhusoodana P.Nambiar Blast-Induced Neurotrauma Branch Center for Military Psychiatry and Neuroscience Walter Reed Army Institute of ResearchSilver Spring MD 20910 USA Analytical Toxicology Division US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground MD21010 USA

PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.

关键词： Paraoxonase 1 catalytic bioscavenger chemical warfare nerve agents pharmacokinetics protective efficacy

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Associations between Bodyweight and Clinical Outcome in Patients Post-Fontan Procedure: A Systematic Review

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Congenital Heart Disease 2022年第6期17卷 617-639页

作者： Emma Payne Thomas Wilson Marjan Haghighi Zoe McCallum Yves d’Udekem Julian Ayer The University of Sydney SydneyAustralia The University of Melbourne MelbourneAustralia The Royal Children’s Hospital MelbourneAustralia The Royal Prince alfred Hospital SydneyAustralia The Children’s National Hospital WashingtonUSA

Background: Patients born with a single ventricle circulation commonly experience growth failure in early life,which is associated with adverse outcomes in infancy. However, associations between bodyweight or weight trajectoryand clinical outcome post-Fontan procedure are yet to be determined. Methods: On the 1st of July 2021, asystematic review was performed in MEDLINE, EMBASE, the Cochrane Library, and Scopus of studies of patientswith clinical outcome data post-Fontan procedure and association with bodyweight. Quality of studies was evaluatedby Newcastle–Ottawa scale for cohort studies and Joanna Briggs institute tool for cross-sectional ***: Of 527 studies that underwent title and abstract screening, 15 were selected for final review. An increasedrisk of adverse post-Fontan outcomes was found for low weight patients, consistent with findings in *** there is some evidence to suggest increased mortality in overweight adult patients, studies are conflictingas to whether overweight status is associated with increased heart failure. Increased BMI is associated with diminishedexercise capacity and deceased physiological functioning. Negative weight trajectory is associated withadverse outcomes in the peri-Fontan period, whereas a positive weight trajectory is associated with increased Fontanfailure in adulthood. Abnormal BMI (high or low) is associated with increased heart failure and poorer performancein quality-of-life scores. Conclusions: Bodyweight is a modifiable risk factor for poor clinical outcomein patients with a single ventricle circulation. Recognizing associations between bodyweight and Fontan pathophysiologymay help to define patient-centered exercise and diet interventions that minimize patient morbidityand mortality.

关键词： Fontan bodyweight congenital heart disease single ventricle

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阿司匹林诱发哮喘的流行情况:系统性综述及临床意义

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英国医学杂志中文版 2004年第4期7卷 213-216页

作者： Christine Jenkins John Costello Linda Hodge 满晓燕黄克武 Woolcock institute of medical research Royal Prince Alfred Hospital Camperdown NSW 2050 Australia head asthma group King's College Hospital London SE5 9RSclinical director of medicine Asthma Centre Royal Prince Alfred Hospitaldietitian

目的对阿司匹林诱发哮喘流行情况及相关综合征进行再评估。资料来源以下数据库:Biosis,SciSearch(1990-2002年3月),Embase(1974-2002年3月),Medline(1966-2002年3月),Toxline,Derwent DrugFile(1964-2002年3月),学术会议论文索引,国际药学摘要,药学在线(1978-2002年3月)。选择标准研究类型,患者人群,评价结果的方法。综述仅限于非处方止痛剂的呼吸道反应。结果与文献记载的阿司匹林诱发哮喘的发生率(成人3％,95％可信区间2％-4％,儿童2％,1％-3％)相比,口服激发试验的阳性率(成人21％,14％-29％,儿童5％,0-4％)最高。大多数阿司匹林诱发哮喘患者对非处方非甾体抗炎药(NSAIDs)存在着交叉过敏:布洛芬,98％;萘普生,100％;双氯芬酸,93％。而只有7％的人对扑热息痛交叉过敏。结论成人阿司匹林诱发哮喘的患病率比过去提出的要高。因此,当临床需要应用阿司匹林或某种非甾体抗炎药(NSAIDs)而不能肯定其安全性时,应做口服激发试验。

关键词：阿司匹林哮喘药物不良反应过敏反应

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Pooled Plasmid Sequencing Reveals the Relationship Between Mobile Genetic Elements and Antimicrobial Resistance Genes in Clinically Isolated Klebsiella pneumoniae

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Genomics, Proteomics & Bioinformatics 2020年第5期18卷 539-548页

作者： Yan Jiang Yanfei Wang Xiaoting Hua Yue Qu Anton Y.Peleg Yunsong Yu Department of Infectious Diseases Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province Hangzhou 310016China Biomedicine Discovery institute Department of MicrobiologyFaculty of MedicineNursing and Health SciencesMonash UniversityMelbourne 3800Australia Department of Infectious Diseases The Alfred Hospital and Central Clinical SchoolMonash UniversityMelbourne 3004Australia

Plasmids remain important microbial components mediating the horizontal gene transfer(HGT)and dissemination of antimicrobial *** systematically explore the relationship between mobile genetic elements(MGEs)and antimicrobial resistance genes(ARGs),a novel strategy using single-molecule real-time(SMRT)sequencing was *** approach was applied to pooled conjugative plasmids from clinically isolated multidrug-resistant(MDR)Klebsiella pneumoniae from a tertiary referral hospital over a 9-month *** conjugative plasmid pool was obtained from transconjugants that acquired antimicrobial resistance after plasmid conjugation with 53 clinical *** plasmid pool was then subjected to SMRT sequencing,and 82 assembled plasmid fragments were *** total,124 ARGs(responsible for resistance to b-lactam,fluoroquinolone,and aminoglycoside,among others)and 317 MGEs[including transposons(Tns),insertion sequences(ISs),and integrons]were derived from these *** of these ARGs were linked to MGEs,allowing for the establishment of a relationship network between MGEs and/or ARGs that can be used to describe the dissemination of resistance by mobile *** elements involved in resistance transposition were identified,including IS26,Tn3,IS903 B,ISEcp1,and *** the most predominant IS in the network,a typical IS26-mediated multi-copy composite transposition event was illustrated by tracing its flanking 8-bp target site duplications(TSDs).The landscape of the pooled plasmid sequences highlights the diversity and complexity of the relationship between MGEs and ARGs,underpinning the clinical value of dominant HGT profiles.

关键词： Horizontal transfer profile Transconjugant Single-molecule real time sequencing Insertion sequence Plasmid

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Kynurenine is an endothelium-derived relaxing factor produced during inflammation

Kynurenine is an endothelium-derived relaxing factor produce...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Gavin McKenzie Paul K Witting Johannes-Peter Stasch Michael Hahn Dechaboon Changsirivathanathamrong Helen J Ball Shane R Thomas Vimal Kapoor David S Celermajer Andrew L Mellor John F Keaney,Jr Nicholas H Hunt Roland Stocker School of medical Sciences University of New South WalesNSW 2052Australia School of medical Sciences(Pathology)and Bosch institute Faculty of MedicineUniversity of SydneyNSW 2006Australia Cardiovascular research Bayer HealthCare WuppertalGermany Medicinal Chemistry Bayer HealthCareWuppertalGermany Centre for Vascular research School of Medical Sciences(Pathology)and Bosch InstituteFaculty of MedicineUniversity of SydneyNSW 2006Australia Centre for Vascular research University of New South WalesNSW 2052Australia School of Medicine and Pharmacology University of Western AustraliaPerth WA 6009Australia Royal Prince alfred Hospital University of SydneyNSW 2006Australia Immunotherapy Center Medical College of GeorgiaAugusta GA 30912U.S.A

＜正＞Control of blood vessel tone is central to vascular *** we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase（Ido） expressed in endothelial cells contributes to arterial vessel relaxation and the control of blood *** of mice with malarial parasites（Plasmodium berghei） or induction of endotoxemia in mice led to endothelial expression of Ido,decreased plasma tryptophan concentration, increased kynurenine concentration and *** inhibition of Ido increased blood pressure in systemically inflamed mice but not in mice deficient in Ido or interferon-γ,which is required for Ido *** tryptophan and kynurenine dilated preconstricted porcine coronary arteries;the dilating effect of tryptophan required the presence of active Ido and an intact endothelium,whereas the effect of kynurenine was endothelium *** arterial relaxation induced by kynurenine was mediated by activation of the adenylate and soluble guanylate cyclase *** administration decreased blood pressure in a dose-dependent manner in spontaneously hypertensive *** results identify tryptophan metabolism by Ido as a new pathway contributing to the regulation of vascular tone.

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Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase Ⅱ randomised placebo-controlled double-blind multicentre trial

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Stroke & Vascular Neurology 2022年第2期7卷 158-165页

作者： Nawaf Yassi Henry Zhao Leonid Churilov Bruce C V Campbell Teddy Wu Henry Ma Andrew Cheung Timothy Kleinig Helen Brown Philip Choi Jiann-Shing Jeng Annemarei Ranta Hao-Kuang Wang Geoffrey C Cloud Rohan Grimley Darshan Shah Neil Spratt Der-Yang Cho Karim Mahawish Lauren Sanders John Worthington Ben Clissold Atte Meretoja Vignan Yogendrakumar Mai Duy Ton Duc Phuc Dang Nguyen Thai My Phuong Huy-Thang Nguyen Chung Y Hsu Gagan Sharma Peter J Mitchell Bernard Yan Mark W Parsons Christopher Levi Geoffrey A Donnan Stephen M Davis Department of Medicine and Neurology Melbourne Brain Centre at The Royal Melbourne HospitalThe University of MelbourneParkvilleVictoriaAustralia Population Health and Immunity Division Walter and Eliza Hall Institute of Medical ResearchParkvilleVictoriaAustralia Ambulance Victoria MelbourneVictoriaAustralia Melbourne medical School The University of MelbourneMelbourneVictoriaAustralia Stroke Division The Florey Institute of Neuroscience and Mental HealthParkvilleVictoriaAustralia Department of Neurology Christchurch HospitalChristchurchNew Zealand Department of Neurology Monash Medical CentreMonash UniversityClaytonVictoriaAustralia Department of Interventional Neuroradiology Liverpool HospitalLiverpoolNew South WalesAustralia Department of Neurology Royal Adelaide HospitalAdelaideSouth AustraliaAustralia Department of Neurology Princess Alexandra HospitalWoolloongabbaQueenslandAustralia Department of Neurology Box Hill HospitalEastern HealthBox HillVictoriaAustralia Stroke Centre and Department of Neurology National Taiwan University HospitalTaipeiTaiwan Department of Medicine Dunedin School of MedicineUniversity of OtagoWellingtonNew Zealand Department of Neurosurgery E-Da HospitalYanchaoKaohsiungTaiwan Department of Neurology Alfred HospitalMelbourneVictoriaAustralia Department of Clinical Neuroscience Monash University Central Clinical SchoolMelbourneVictoriaAustralia Department of Medicine Sunshine Coast University HospitalNambourQueenslandAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia Department of Neurology John Hunter HospitalThe University of NewcastleNewcastleNew South WalesAustralia Department of Neurosurgery China Medical University HospitalTaichungTaiwan Department of Internal Medicine Palmerston North HospitalPalmerston NorthNew Zealand Department of Neurology St Vincent's HospitalFitzroyVictoriaAustralia Department of Neurology Royal Prince Alfred HospitalCamperdownNew South WalesAustra

Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of *** acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma *** and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical *** In patients with spontaneous ICH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with *** size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of *** adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 *** Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching *** efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up CT *** We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with ICH within 2 hours from onset,based in participating mobile stroke units and emergency departments.

关键词： placebo centre absolute

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Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford

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World Journal of Gastroenterology 2020年第30期26卷 4428-4441页

作者： Samba Siva Reddy Pulusu Ashish Srinivasan Krupa Krishnaprasad Daniel Cheng Jakob Begun CharlotteKeung Daniel Van Langenberg Lena Thin Tamara Mogilevski Peter De Cruz Graham Radford-Smith Emma Flanagan Sally Bell Soleiman Kashkooli Miles Sparrow Simon Ghaly Peter Bampton Elise Sawyer Susan Connor Quart-ul-ain Rizvi Jane M Andrews Gillian Mahy Paola Chivers Simon Travis Ian Craig Lawrance Centre for Inflammatory Bowel Diseases St John of God HospitalSubiaco 6008Western AustraliaAustralia Translational Gastroenterology Unit NIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Inflammatory Bowel Disease research Group Queensland institute of Medical ResearchHerston 4006QueenslandAustralia Department of Gastroenterology Mater HospitalBrisbane 4101QueenslandAustralia Department of Gastroenterology Mater HospitalSouth Brisbane 4101QueenslandAustralia of Gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of Gastroenterology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalFitzroy 3065VictoriaAustralia Department of Gastroenterology Northern HealthEpping 3076VictoriaAustralia Department of Gastroenterology The Alfred HospitalMelbourne 3004VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalDarlinghurst 2010New South WalesAustralia Department of Gastroenterology Flinders Medical CentreBedford Park 5042South AustraliaAustralia Department of Gastroenterology Liverpool HospitalSydney 2170New South WalesAustralia Department of Gastroenterology Royal Adelaide Hospital&University of AdelaideAdelaide 5000South AustraliaAustralia Department of Gastroenterology Townsville HospitalDouglas 4814QueenslandAustralia institute for Health research University of Notre DameFremantle 6160Western AustraliaAustralia School of Medicine and Pharmacology University of Western AustraliaCrawley 6009Western AustraliaAustralia

BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)*** To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving *** A retrospective review of Australian and Oxford,United Kingdom data for UC *** response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were *** regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing *** outcomes were *** Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were *** clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo ***-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%P<0.001,6 mo 73%vs 46%P<0.001,12 mo 66%vs 51%P=0.03).More Australian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 *** VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

关键词： Vedolizumab Ulcerative colitis Outcomes

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Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation

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World Journal of Gastroenterology 2014年第36期20卷 13088-13104页

作者： Devanshi Seth Alastair Duly Paul C Kuo Geoffrey W McCaughan Paul S Haber Drug Health Services Royal Prince Alfred Hospital Camperdown NSW 2050 Australia Garvan institute Darlinghurst NSW 2010 Australia Central Clinical School of Medicine the University of Sydney Sydney NSW 2050 Australia Department of Surgery Loyola University Medica Centre Maywood IL 60153 United States AW Morrow Gastroenterology and Liver Centre RPAH Camperdown NSW 2050 Australia

AIM: To investigate over-expression of Osteopontin (OPN) pathway expression and mechanisms of action in human alcoholic liver disease (ALD), in vivo and in vitro acute alcohol models.

关键词： Hepatic stellate cells Liver cirrhosis Plasmin Steatosis Fibrogenesis Transforming growth factor β Osteopontin isoform

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The model of cytokine release syndrome in CAR T-cell treatment for B-cell non-Hodgkin lymphoma

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1295-1303页

作者： Jianshu Wei Yang Liu Chunmeng Wang Yajing Zhang Chuan Tong Guanghai Dai Wei Wang John E.J.Rasko J.Joseph Melenhorst Wenbin Qian Aibin Liang Weidong Han Department of Bio-therapeutic the First Medical CenterChinese PLA General Hospital100853 BeijingChina Department of Oncology the first Medical CenterChinese PLA General Hospital100853 BeijingChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China Collaborative Innovation Center for Biotherapy Chengdu 610041China Department of Cell and Molecular Therapies Royal Prince Alfred HospitalSydneyNSW 2006Australia Gene and Stem Cell Therapy Program Centenary InstituteUniversity of SydneySydneyNSW 2006Australia Central Clinical School Faculty of Medicine and HealthThe University of SydneyCamperdownNSW 2050Australia Department of Pathology and Laboratory Medicine Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104-515USA Department of Hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310009China Department of Hematology Shanghai Tongji HospitalTongji University School of MedicineShanghai 200065China State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases100853 BeijingChina

Chimeric antigen receptor T(CAR T)cell therapy has demonstrated efficacy in the treatment of haematologic ***,the accompanying adverse events,the most common of which is cytokine release syndrome(CRS),substantially limit its wide *** to its unique physiological characteristics,CRS in CAR T-cell treatment for B-cell non-Hodgkin lymphoma(BNHL)may exhibit some special *** existing guidelines had greatly promoted the recognition and management of CRS,many recommendations are not fully applicable to ***,it is imperative to identify responses that are specific to CRS observed following CAR T treatment for *** on underlying biological processes and known pathophysiological mechanisms,we tentatively propose a new model to illustrate the occurrence and evolution of CAR T-cell-therapy-related CRS in *** this model,tumour burden and bone marrow suppression are considered determinants of *** phenomena after CAR T-cell infusion(such as local inflammatory response)are further *** proposed model will help us better understand the basic biology of CRS and recognize and manage it more rationally.

关键词： cytokine lymphoma treatment

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