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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK department of Neurology Oslo University HospitalOsloNorway Research and development Norwegian Air Ambulance FoundationOsloNorway department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5d,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(Sd),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWd)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWd 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREAdY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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3-dimensional Kinematic Comparison of Arm Movements between an Individual with NGLY1 deficiency and a Neurotypical Individual

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Case Reports in Clinical Medicine 2024年第4期13卷 122-146页

作者： Charles S. Layne christopher A. Malaya Brock Futrell dacia Martinez diaz Christian Alfaro Hannah E. Gustafson Subhalakshmi Chandrasekaran Rhea M. Phatak Bernhard Suter department of Health and Human Performance University of Houston Houston TX USA Center for Neuromotor and Biomechanics Research University of Houston Houston TX USA Center for Neuro Engineering and Cognitive Science University of Houston Houston TX USA department of Computer Science and Engineering Texas A&M University College Station TX USA Blue Bird Circle Rett Center Texas Children&#8217s Hospital Houston TX USA Baylor College of Medicine Houston TX USA

NGLY1 deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3d initiation area as a percentage of the complete movement. The stati

关键词： NGLY1 deficiency developmental disorders Kinematics 3 dimensional Analyses

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Cardiac remodeling as a consequence of atrial fibrillation： An anatomical study of perfusion-fixed human heart specimens

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Journal of Geriatric Cardiology 2011年第3期8卷 141-146页

作者： christopher d Rolfes Stephen A Howard Ryan P Golf Paul A Iaizzo department of Biomedical Engineering University of Minnesota Minneapolis MAr 55455 USA department of Surgery University of Minnesota Minneapolis MN55455 USA department of Integrative Biology and Physiology University of Minnesota Minneapolis MN 55455 USA

Background Atrial fibrillation （AF） causes a continuum of atrial anatomical remodeling. Methods Using a library of perfusion-fixed human hearts, specimens with AF were compared to controls. during this preliminary assessment study, direct measurements were taken of atrial volume, pulmonary vein （PV） circumference, and left atrial （LA） wall thicknesses. Results Hearts with AF typically had larger atrial volumes, as well as a much larger variation in volume compared to controls （range of 59.6-227.1 mL in AF hearts compared to 65.1-115.9 mL in controls）. For all hearts, right PVs were larger than left PVs （mean： 171.4 ± 84.6 mm^2 for right and 1182 ± 50.1 mm^2 for left, P 〈 0.005）. LA wall thicknesses ranged from 0.7 mm to 3.1 mm for both AF and control hearts. Conclusions Hearts with AF had a large range of sizes which is consistent with the progression of atrial remodeling during AF. The large range of thicknesses will influence the amount of energy needed to create transmural lesions during ablation procedures.

关键词： left atrial dimensions volumes pulmonary vein ostia atrial fibrillation

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SARS-CoV-2 RBd and Its Variants Can Induce Platelet Activation and Clearance:Implications for Antibody Therapy and Vaccinations against COVId-19

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Research 2024年第3期2023卷 1-15页

作者： Xiaoying Ma Jady Liang Guangheng Zhu Preeti Bhoria Aron A.Shoara daniel T.MacKeigan christopher J.Khoury Sladjana Slavkovicl Lisha Lin danielle Karakas Ziyan Chen Viktor Prifti Zhenze Liu Chuanbin Shen Yuchong Li Cheng Zhang Jiayu dou Zack Rousseau Jiamin Zhang Tiffany Ni Xi Lei Pingguo Chen Xiaoyu Wu Hamed Shaykhalishahi Samira Mubareka Kim AConnelly Haibo Zhang Ori Rotstein Heyu Ni department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada department of Laboratory Medicine Keenan Research Centre for Biomedical Science of St.Michael’s HospitalTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada department of Physiology University of TorontoTorontoONCanada CCOA Therapeutics Inc. TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada The State Key Laboratory of Respiratory disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina department of Laboratory Medicine The Second Affliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina Advanced Pharmaceutics&drug delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoONCanada department of Medical Microbiology and Infectious disease Sunnybrook Health Science CentreToronto ONCanada department of Medicine University of TorontoTorontoONCanada division of Cardiology.St.Michael's Hospital TorontoONCanada department of Anesthesiology and Pain Medicine and division of Critical Care Medicine University of TorontoTorontoONCanada interdepartmental division of Critical Care Medicine University of TorontoTorontoONCanada department of Surgery University of Toronto TorontoONCanada.

The COVId-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health *** cases of COVId-19 and the rare cases of COVId-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately *** infection and vaccination utilize the spike protein receptor-binding domain(RBd)of *** found that intravenous injection of recombinant RBd caused significant platelet clearance in *** investigation revealed the RBd could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the delta and Kappa *** RBd–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−***,RBd binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGd(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBd polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBd-induced platelet activation,aggregation,and clearance in vivo,and SARS-CoV-2 infection and replication in Vero E6 *** data show that the RBd can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVId-19 and *** newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVId-19.

关键词： Antibody diagnosis vaccine

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Structure and activity of thermophilic methanogenic microbial communities exposed to quaternary ammonium sanitizer

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Journal of Environmental Sciences 2017年第6期29卷 164-168页

作者： Jesus d.Fernandez-Bayo Juliano Toniato Blake A.Simmons christopher W.Simmons department of Food Science and Technology University of CaliforniaDauisCA 95616USA department of Biological and Agricultural Engineering Uniuersity of CaliforniaDauisCA 95616USA Joint BioEnergy Institute EmeryvilleCA 94608USA Biological and Engineering Sciences Center Sandia National LaboratoriesLiuermoreCA 94551USA Energy Efficiency Center University of CaliforniaDauisCA 95616USA

Food processing facilities often use antimicrobial quaternary ammonium compound （QAC） sanitizers to maintain cleanliness. These QACs can end up in wastewaters used as feedstock for anaerobic digestion. The aim of this study was to measure the effect of QAC contamination on biogas production and structure of microbial communities in thermo- philic digester sludge. Methane production and biogas quality data were analyzed in batch anaerobic digesters containing QAC at 0, 15, 50, 100 and 150 mg/L. Increasing sanitizer concentration in the bioreactors negatively impacted methane production rate and biogas quality. Microbial community composition data was obtained through 16S rRNA gene sequencing from the QAG-contaminated sludges. Sequencing data showed no significant restructuring of the bacterial communities. However, significant restructuring was observed within the archaeal communities as QAC concentration increased. Further studies to confirm these effects on a larger scale and with a longer retention time are necessary.

关键词： Anaerobic digestionAntimicrobialsBiofuelsMicrobial ecologyWaste management

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Heterozygous carriers of galactocerebrosidase mutations that cause Krabbe disease have impaired microglial function and defective repair of myelin damage

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Neural Regeneration Research 2018年第3期13卷 393-401页

作者： Nicole J.Scott-Hewitt christopher J.Folts Mark d.Noble department of Biomedical Genetics University of Rochester School of Medicine and Dentistry

This review addresses two puzzling findings related to mutations in galactocerebrosidase （GALC） that cause Krabbe disease （Kd）, a severe lysosomal storage disorder characterized by extensive myelin damage in children with mutations in both GALC alleles. First, heterozygous carriers of Kd-causing mutations, which include the biological parents of children with Kd, exhibit increased risk for developing other diseases. Second, variants in the GALC locus increase the risk of developing multiple sclerosis （MS）, another disease characterized by extensive myelin damage. What explains these correlations？ In studies on cuprizone-induced myelin damage in heterozygous （GALC＋/–） mice carrying one copy of a mutation that causes Kd-like disease, the extent of damage was similar in GALC＋/– and wild-type （WT） mice. In contrast, GALC＋/- mice had striking defects in repair of cuprizone-induced damage. We further found unexpected microglial defects in myelin debris clearance and in the ability to up-regulate the Trem2 microglial protein critical for debris uptake. These defects were rescued by exposure to a lysosomal re-acidifying drug discovered in our studies on Kd, and which provides multiple clinically relevant benefits in the twitcher （GALC＋/–） mouse model of Kd. Thus, heterozygous GALC mutations cause effects on biological function that may help to understand the increased disease risk in heterozygous carriers of such mutations and to understand why GALC variations increase the risk of MS. Our findings indicate that while some genetic risk factors may contribute to complex diseases by increasing the risk of tissue damage, others may do so by compromising tissue repair.

关键词： vulnerability locus multiple sclerosis Krabbe disease galactocerebrosidase microglia myelin repair lysosomal storage disorders heterozygous carriers Trem2 demyelination

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distal triceps injuries(including snapping triceps):A systematic review of the literature

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世界骨科杂志：英文版 2017年第6期8卷 507-513页

作者： Kimberley Shuttlewood James Beazley christopher d Smith Royal devon and Exeter Hospital

AIM To review current literature on types of distal triceps injuryand determine diagnosis and appropriate *** We performed a systematic review in PubM ed, Cochrane and EMBASE using the terms distal triceps tears and snapping triceps on the 10 th January 2017. We excluded all animal, review, foreign language and repeat papers. We reviewed all papers for relevance and of the papers left we were able to establish the types of distal triceps injury, how these injuries are diagnosed and investigated and the types of management of these injuries including surgical. The results are then presented in a review paper *** Three hundred and seventy-nine papers were identified of which 65 were relevant to distal triceps injuries. After exclusion we had 47 appropriate papers. The papers highlighted 2 main distal triceps injuries: distal triceps tears and snapping triceps. Triceps tear are more common in males than females occurring in the 4th-5th decade of life and often due to a direct trauma but are also strongly associated with weightlifting and American football. The tears are diagnosed by history and clinically with a palpable gap. diagnosis can be confirmed with the use of ultrasound(US) and magnetic resonance imaging. Treatment depends on type of tear. Partial tears can be treated conservatively with bracing and physio whereas acute tears need repair either open or arthroscopic using suture anchor or bone tunnel techniques with similar success. Chronic tears often need augmenting with tendon allograft or autograft. Snapping triceps are also seen more in men than women but at a mean age of 32 years. They are characterized by a snapping sensation mostly medially and can be associated with ulna nerve subluxation and ulna nerve symptoms. US is the diagnostic modality of choice due to its dynamic nature and to differentiate between snapping triceps tendon or ulna nerve. Treatment is conservative initially with activity avoidance and if that fails surgi

关键词： Triceps distal Tear Rupture Snapping Partial thickness Biomechanical Anatomy

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Ultra-small Cu nanoparticles embedded in N-doped carbon arrays for electrocatalytic CO2 reduction reaction in dimethylformamide

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Nano Research 2018年第7期11卷 3678-3690页

作者： Xiaolong Zhang Ying Zhang Fengwang Li christopher d. Easton Alan M. Bond Jie Zhang School of Chemistry Monash University Clayton 3800 VIC Australia ARC Centre of Excellence for Electromaterials Science Monash University Clayton 3800 VIC Australia CSIRO Manufacturing BayviewAvenue Clayton 3168 VIC Australia

The development of heterogeneous catalysts with a well-defined micro structure to promote their activity and stability for electrocatalyfic CO2 reduction has been shown to be a promising strategy. In this work, Cu nanoparticles （- 4 nm in diameter） embedded in N-doped carbon （Cu@NC） arrays were fabricated by thermal decomposition of copper tetracyanoquinodimethane （CuTCNQ） under N2. Compared to polycrystalline copper electrodes, the Cu@NC arrays provide a significantly improved number of catalytically active sites. This resulted in a 0.7 V positive shift in onset potential, producing a catalytic current density an order magnitude larger at a potential of -2.7 V vs. Fc/Fc＋（Fc = ferrocene） in dimethylformamide （dMF）. By controlling the water content in the dMF solvent, the CO2 reduction product distribution can be tuned. Under optimal conditions （0.5 vol.% water）, 64% HCOO^-, 20% CO, and 13% H2 were obtained. The Cu@NC arrays exhibited excellent catalytic stability with only a 0.5% decrease in the steady-state catalytic current during 6 h of electrolysis. The three-dimensional （3d） array structure of the Cu@NC was demonstrated to be effective for improving the catalytic activity of copper based catalysts while maintaining long-term catalytic stability.

关键词： copper tetracyanoquinodimethane (CuTCNQ) copper carbon arrays CO2 reduction electrocatalysis

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Suicide transport blockade of motor neuron survival generates a focal graded injury and functional deficit

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Neural Regeneration Research 2021年第7期16卷 1281-1287页

作者： Allison S.Liang Joanna E.Pagano christopher A.Chrzan Randall d.McKinnon department of Neurosurgery Rutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA Member The Cancer Institute of New JerseyNew BrunswickNJUSA

We describe a pre-clinical spinal cord motor neuron injury model that is minimal invasive, reproducible, focal and easily applied to small *** axonal transport of a pro-apoptotic phosphatidylinosotol 3'-kinase inhibitor, wortmannin, via the sciatic nerve results in loss of ipsilateral lumbar motor neurons proportional to the level of drug *** neuron loss was detected by choline acetyltransferase(ChAT) immunostaining and with a transgenic thy1-eGFP *** short half-life of wortmannin generates minimal wound spread, and wortmannin does not affect axon transport, as determined by co-injection of a pseudorabies virus *** quantitative transcript analysis, we found that ChAT transcripts significantly decreased at 14 days post-delivery of 1 μg wortmannin, relative to sham controls, and remained low after 90 *** effects were observed with 200 ng and 100 ng *** also generated a transient and significant increase in astrocyte Gfap transcripts after 14 days with a return to control levels at 90 *** mice had hind limb spasticity and a forced motor function defect that was quantified using a water exit *** rapidly exit a shallow water tray, and wortmannin treated animals were up to 12-fold slower, a phenotype that persisted for at least 3 *** the focal delivery of wortmannin to motor neurons generates a reproducible and scalable injury that can facilitate quantitative studies on neural regeneration and *** efficacy of sciatic nerve suicide transport can also explain neurotoxin-mediated selective loss of motor neurons in diseases such as amyotrophic lateral *** procedures were performed at Rutgers under established Institutional Animal Care and Use protocols(eIACUC_TR201800022, approved on March 20, 2018).

关键词： amyotrophic lateral sclerosis injury motor function motor neuron PI3'kinase sciatic nerve suicide transport wortmannin

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diabetes is associated with increased risk of hepatocellular carcinoma in non-alcoholic steatohepatitis with cirrhosis-implications for surveillance and future pharmacotherapy

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Hepatobiliary Surgery and Nutrition 2020年第2期9卷 230-234页

作者： Michael P.Johnston Janisha Patel christopher d.Byrne department of Hepatology University Hospital Southampton NHS Foundation TrustSouthamptonUK Human development and Health Faculty of MedicineUniversity of SouthamptonSouthamptonUK National Institute for Health Research Southampton Biomedical Research Centre University of Southampton and University Hospital Southampton NHS Foundation TrustSouthamptonUK

Hepatocellular carcinoma(HCC)is the most common liver-related complication seen in patients with non-alcoholic fatty liver disease(NAFLd)and non-alcoholic steatohepatitis(NASH)(1).NASH is strongly associated with type 2 diabetes mellitus(T2dM)but it has also been apparent for a number of years that T2dM is associated with an increased risk of HCC independent of the presence of NASH(2).A 2006 meta-analysis of retrospective cohort studies and case-control studies demonstrated an association between T2dM and an increased risk of HCC(3).International guidelines advocate surveillance for HCC in patients with NASH who have progressed to cirrhosis(4).An important clinical question is whether T2dM confers an increased risk of HCC once patients with NASH have progressed to *** a recent study by Yang and colleagues(5),the authors reported strong evidence that T2dM is an independent risk factor for HCC in patients with NASH-related *** and colleagues performed a retrospective analysis of a prospectively registered research dataset of patients with NASH-related cirrhosis.

关键词： T2dM cirrhosis patients

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