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Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes

Microsystems & Nanoengineering 2021年第2期7卷 59-69页

作者： Zeyu Wang Haichen Wang Ryan Becker Joseph Rufo Shujie Yang Brian E.Mace Mengxi Wu Jun Zou daniel t.laskowitz tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC27708USA Department of Neurology Duke UniversityDurhamNC27708USA Department of Biomedical Engineering Duke UniversityDurhamNC27708USA Department of Geriatrics Duke UniversityDurhamNC27708USA Department of Electrical&Computer Engineering Texas A&M UniversityCollege StationTX77840USA

traumatic brain injury(tBI)is a global cause of morbidity and *** management and risk stratification of patients with tBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available,noninvasive diagnostic *** particular,a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild tBI(mtBI).Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue *** applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after *** isolation eliminated interference from other blood components,making it possible to detect exosomal biomarkers for tBI via flow *** cytometry analysis indicated that exosomal biomarkers for tBI increase in the first 24 h following head trauma,indicating the potential of using circulating exosomes for the rapid diagnosis of *** levels of tBI biomarkers were only detected in the samples separated via acoustofluidics;no changes were observed in the analysis of the raw plasma *** finding demonstrated the necessity of sample purification prior to exosomal biomarker *** acoustofluidic exosome separation can easily be integrated with downstream analysis methods,it shows great potential for improving early diagnosis and treatment decisions associated with tBI.

关键词： diagnosis separation injury

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拟apoE对小鼠蛛网膜下腔出血及脑血管痉挛的治疗作用

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第四军医大学学报 2007年第12期28卷 1071-1074页

作者：高俊玲高福禄 daniel t.laskowitz 河北医科大学组织学与胚胎学教研室承德医学院组织学与胚胎学教研室 Multidisciplinary Neuroprotection Laboratories Duke University Medical CenterDurhamNC27710

目的:探讨新合成的拟载脂蛋白E(apoE)对蛛网膜下腔出血(SAH)的治疗作用及机制.方法:55只C57BL6/JL小鼠随机分为:假手术组,SAH组,低剂量(SAH+apoE-1410,0.6mg/Kg)组和高剂量(SAH+apoE-1410,1.2mg/Kg)组.显微操作戳破右侧大脑中动脉(MCA)和大脑前动脉(ACA)分叉处造成SAH模型.术后30min开始经尾静脉给药,每12h一次,连用3d.每日检测小鼠的一般精神状态、神经功能评分、综合运动能力评分.术后第3日测量MCA直径.结果:术后SAH组小鼠精神萎靡,食欲下降,有的难进食水,体质量下降,死亡率为42.8%.高、低剂量组与SAH组比较,一般症状明显减轻,死亡率分别为14.2%和18.8%,与SAH组比较,显著降低(P0.05).综合运动能力评分在SAH组(58.8±25.7)明显低于假手术组(272.2±25.7,P<0.05);高剂量组(95.5±13.2),低剂量组(95.6±18.5)的综合运动能力分别明显高于单纯SAH组(58.8±20.9,P<0.05).结论:外源性拟apoE对SAH及脑血管痉挛有一定的治疗作用,其机制与降低神经系统对损伤的炎性反应有关,拟apoE有可能成为治疗SAH的新措施.

关键词：蛛网膜下腔出血拟apoE apoE基因脑血管痉孪

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神经重症患者感染诊治:美国临床神经医学手册(2017-2018)与中国专家共识(2017)的对比与解读

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中华神经医学杂志 2019年第1期18卷 2-11页

作者：葛歆瞳 daniel t.laskowitz 江荣才张建宁天津医科大学总医院神经外科、天津市神经病学研究所 300052 美国杜克大学医学中心神经内科、美国杜克大学医学院神经生物学系达勒姆27710

一、总论医院获得性感染(HAI)是医院内,尤其是重症监护病房(ICU)内患者的重要致死原因。神经重症监护病房(NICU)患者的感染多属于HAI,其发生与神经外科手术(如脑室外引流术)、机械通气、动脉导管的应用及类固醇/巴比妥类药物的使用密... 详细信息

一、总论医院获得性感染(HAI)是医院内,尤其是重症监护病房(ICU)内患者的重要致死原因。神经重症监护病房(NICU)患者的感染多属于HAI,其发生与神经外科手术(如脑室外引流术)、机械通气、动脉导管的应用及类固醇/巴比妥类药物的使用密切相关,其主要类型为中枢神经系统感染、手术切口感染、医院获得性肺炎(HAP)及呼吸机相关性肺炎(VAP),此外还包括尿路感染、导管相关性血流感染、消化道感染及压疮等。美国临床神经医学(HCN)手册指出,NICU中HAI的发病率为20%-30%,其是否发生及严重程度与NICU患者预后密切相关。在一项针对神经外科术后HAI患者的前瞻性观察队列研究中,NICU患者死亡率同HAI发病率显著相关,其相对危险度为2.04(95%置信区间:1.30-3.20,P<0.05)。此外,NICU感染患者的住院天数(中位数:54 d)显著高于未感染患者(中位数:11 d;P<0.05)。中国专家共识引用赵继宗院士牵头的研究指出,伴开放性颅骨骨折、头皮裂伤的脑外伤或头皮裂伤超过4 h的患者,手术部位感染发生率为10%-25%;清洁-污染手术(包括进入窦或乳突的手术、修补开放性颅骨骨折或无菌技术有明显缺陷的手术)感染发生率为6.8%-15.0%;清洁手术感染发生率为2.6%-5.0%。

关键词：神经重症监护感染美国临床神经医学手册中国专家共识

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Apolipoprotein E mimetic peptide CN-105 improves outcome in a murine model of SAH

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Stroke & Vascular Neurology 2018年第4期3卷 222-230页

作者： Ji Liu Guanen Zhou Bradley J Kolls Yanli tan Chuan Fang Haichen Wang daniel t.laskowitz Department of Neurology Huanhu HospitalTianjinChina Department of Neurology Duke University School of MedicineDurhamNorth CarolinaUSA Department of Pathology Basic Medical College of HeBei UniversityBaodingChina Department of Neurosurgery The Affiliated Hospital of HeBei UniversityBaodingChina Department of Neurobiology Duke University Medical CenterDurhamNorth CarolinaUSA Department of Anesthesiology Duke University School of MedicineDurhamNorth CarolinaUSA

Objective Subarachnoid haemorrhage(SAH)accounts for 3%of all strokes,and is associated with significant morbidity and *** is growing evidence implicating apolipoprotein E(apoE)in mediating adaptive anti-inflammatory and neuroprotective responses following ischaemic and traumatic brain *** the current study,we test the efficacy of a small apoE mimetic peptide,CN-105 in a murine model of *** Mice subjected to SAH received repeated intravenous injections of CN-105 every 12 hours for 3 days,with the first dose given 2 hours after *** functional outcomes were assessed by rotarod and neurological severity *** grade and cerebral vascular diameters were measured at 5 days *** microgliosis,neuronal degeneration and survival were analysed at 5 and 35 days post-SAH,*** CN-105 reduces histological evidence of inflammation,reduces vasospasm and neuronal injury and is associated with improved long-term behavioural outcomes in a murine model of *** Given its favourable pharmacokinetic profile,central nervous system penetration and demonstration of clinical safety,CN-105 represents an attractive therapeutic candidate for treatment of brain injury associated with SAH.

关键词： protective degeneration inflammation

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LDL-C levels,lipid-lowering treatment and recurrent stroke in minor ischaemic stroke or tIA

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Stroke & Vascular Neurology 2022年第4期7卷 276-284页

作者： Yuesong Pan Runqi Wangqin Hao Li Aoming Jin Jiejie Li Jinxi Lin Xia Meng Ying Xian daniel t.laskowitz Yongjun Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Department of Neurology Duke University Medical CenterDurhamNCUSA Department of Neurology UT Southwestern Medical CenterDallasTexasUSA Duke Clinical Research Institute DurhamNorth CarolinaUSA Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina Center for Excellence in Brain Science and Intelligence technology Chinese Academy of SciencesShanghaiChina

Background and purpose Dyslipidaemia is a major risk factor for ischaemic stroke and transient ischaemic attack(tIA).this study aimed to investigate the association between baseline low-density lipoprotein cholesterol(LDL-C)level,lipid-lowering treatment and short-term risk of new stroke in patients with a minor ischaemic stroke or *** We derived data from the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events *** with a minor stroke or tIA were categorised by LDL-C level at baseline(th or without lipid-lowering treatment after symptom *** primary outcome was a new ischaemic stroke at 3 *** association of baseline LDL-C level,lowering treatment and outcomes were *** Among 3027 patients,2154(71.2%)patients had an initial LDL-C≥2.6 mmol/L,of which 1267(41.9%)received lipid-lowering *** LDL-C level was associated with a higher risk of new ischaemic stroke at 3 months in patients without lipid-lowering treatment(***=1.35,95%CI:1.19 to 1.53),but not in those with lipid-lowering treatment(***=0.99,95%CI:0.82 to 1.19)(p for interaction=0.007).Patients with LDL-C≥2.6 mmol/L had a numerically higher risk of ischaemic stroke(11.8%vs 8.0%,***=1.37,95%CI:0.96 to 1.96)in those without lipid-lowering *** patients with LDL-C≥2.6 mmol/L,lipid-lowering treatment was associated with reduced risk of ischaemic stroke at 3 months(7.9%vs 11.8%;***=0.54,95%CI:0.39 to 0.75).Conclusions Elevated untreated baseline LDL-C level was associated with an increased short-term risk of ischaemic stroke among patients presenting with minor ischaemic stroke or *** was potential benefit of lipid-lowering treatment in minor stroke or tIA patients with LDL-C≥2.6 mmol/*** registration number NCt00979589.

关键词： ischaemic treatment Acute

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Emergency medical services use and its association with acute ischaemic stroke evaluation and treatment in Singapore

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Stroke & Vascular Neurology 2020年第2期5卷 121-127页

作者： Hanzhang Xu Ying Xian Fung Peng Woon Janet Prvu Bettger daniel t.laskowitz Yih Yng Ng Marcus Eng Hock Ong David Bruce Matchar Deidre Anne De Silva Department of Family Medicine and Community Health Duke University School of MedicineDurhamNorth CarolinaUnited States Duke University School of Nursing DurhamNorth CarolinaUnited States Duke Clinical Research Institute DurhamNorth CarolinaUnited States Department of Neurology Duke University School of MedicineDurhamNorth CarolinaUnited States Department of Neurology National Neuroscience Institute-Singapore General Hospital CampusSingapore Department of Orthopaedic Surgery Duke University School of MedicineDurhamNorth CarolinaUnited States Hometeam Government of Singapore Ministry of Home AffairsSingapore Department of Emergency Medicine Singapore General HospitalSingapore Program in Health Services and Systems Research Duke-NUS Graduate Medical SchoolSingapore Department of Medicine(General Internal Medicine) Duke University School of MedicineDurhamNorth CarolinaUnited States

Background Emergency medical services(EMS)is a critical link in the chain of stroke *** aimed to assess EMS use for stroke in Singapore,identify characteristics associated with EMS use and the association of EMS use with stroke evaluation and *** the Singapore Stroke Registry combines nationwide EMS and public hospital data for stroke cases in *** regressions with the generalised estimating equations were performed to examine the association between EMS use and timely stroke evaluation and *** Of 3555 acute ischaemic patients with symptom onset within 24 hours admitted to all five public hospitals between 2015 and 2016,68%arrived via *** who used EMS were older,were less likely to be female,had higher stroke severity by National Institute of Health Stroke Scale and had a higher prevalence of atrial fibrillation or peripheral arterial *** transported by EMS were more likely to receive rapid evaluation(door-to imaging time≤25 min 34.3%vs 11.1%,OR=2.74(95%CI 1.40 to 5.38))and were more likely to receive intravenous tissue plasminogen activator(tPA,22.8%vs 4.6%,OR=4.61(95%CI 3.52 to 6.03)).Among patients treated with tPA,patients who arrived via EMS were more likely to receive timely treatment than self-transported patients(door-to needle time≤60 min 52.6%vs 29.4%,OR=2.58(95%CI 1.35 to 4.92)).Conclusions EMS use is associated with timely stroke evaluation and treatment in *** EMS-Hospital stroke pathways and targeted public campaigns to advocate for appropriate EMS use have the potential to improve acute stroke care.

关键词： needle treatment likely

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Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system

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Asian Journal of Andrology 2018年第2期20卷 120-130页

作者： t Hugh Jones daniel M Kelly Robert Hague Centre for Diabetes and Endocrinology Barnsley Hospital NHS Foundation Trust Barnsley UK Academic Unit of Diabetes Endocrinology and Metabolism Department of Oncology and Metabolism University of Sheffield Medical School Sheffield UK Biomedical Research Centre Sheffield Hallam University Sheffield UK

testosterone deficiency is common in men with cardiovascular disease （CVD）, and randomized placebo-controlled trials （RCts） have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise （VO2m,x） and muscle strength in chronic heart failure （CHF）, shortening of the Q-t interval, and improvement of some cardiovascular risk factors. testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCts. testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade （L-calcium channel） and stimulates potassium channel opening by direct nongenomic mechanisms. testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. testosterone improves cardiac output, functional exercise capacity, VO2m=x and vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the

关键词： cardiovascular testosterone testosterone replacement

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Humans influence shrimp movement: a conservation behavior case study with "Shrimp Watching" ecotourism

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Current Zoology 2022年第2期68卷 169-176页

作者： Watcharapong HONGJAMRASSILP daniel t.BLUMStEIN Department of Ecology and Evolutionary Biology University of California Los AngelesLos AngelesCA 90095-1606USA

An increase in ecotourism adversely impacts many animals and contributes to biodiversity *** mitigate these impacts,we illustrate the application of a conservation behavior framework toward the development of a sustainable ecotourism management *** Ubon Ratchathani,thailand,thousands of tourists annually come to see a unique mass migration of shrimps on land(referred to as"shrimp parading").Preliminary work suggests that this tourism has negatively impacted the *** reduce tourism-related impacts we studied:1)the decisions shrimps make when parading and 2)how shrimps respond to different light intensities and *** created an artificial stream and tested the conditions that influence parading by experimentally varying the presence of light and systematically manipulating water velocity(10,60,and 100cm/s).Additionally,we conducted an in situ experiment to study how shrimps respond to tourists'lights under three intensities(50,400,and 9,000 lux)and five colors(white,blue,green,orange,and red).We found most shrimps prefer to leave the river when it is dark and there is low water *** responded the least to red (λmax=630 nm>and orange(λmax=625 nm)light at 50 *** findings were used to develop a management plan by creating three different tourist zones,which maximize tourist needs and minimize the anthropogenic impacts on the *** work could be used as an example of the application of conservation behavior framework in developing management plan for sustainable ecotourism for other invertebrate taxa.

关键词： anthropogenic light caridean shrimps collective behavior freshwater prawn migration nature-based tourism

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Anti-predator behavior along elevational and latitudinal gradients in dark-eyed juncos

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Current Zoology 2020年第3期66卷 239-245页

作者： Madelin ANDRADE daniel t.BLUMStEIN Department of Ecology and Evolutionary Biology University of California621 Young Drive SouthLos AngelesCA 90095-1606USA

Flight-initiation distance(FID),the distance between an individual and experimenter when it begins to flee,can be used to quantify *** other factors,prior studies have shown that latitude explains significant variation in avian FID:at lower latitudes,individuals and species have longer FIDs than those living at higher *** prior studies have focused on the effect of elevation on *** the similar patterns of seasonality,climate,and potentially predator density,that covary between latitude and elevation,birds at higher elevations might tolerate closer *** asked whether elevation or latitude would explain more variation in the FID of a common passerine bird species,dark-eyed juncos(Junco hyemalis).Juncos live in a variety of habitats along both latitudinal and elevational *** found that statistical models containing elevation as a variable explained more of the variation in FID than did models containing *** also found,unexpectedly,that birds at higher elevation fled at greater *** more predators were sighted per hour at higher elevations than at lower elevations,the frequency of predator sightings did not explain a significant amount of variation in *** result questions whether predator density is the main driver of risk perception along elevational ***,because elevation explains more variation in FID than latitude in at least one species,these findings have direct implications on how human impacts on birds are ***,those designing set-back zones to reduce human impact on birds may consider modifying them based on both latitude and elevation.

关键词： antipredator behavior FID latitude elevation dark-eyed junco Junco hyemalis

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Experimental studies on the erosion rate of different heat treated carbon steel economiser tubes of power boilers by fly ash particles

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International Journal of Minerals,Metallurgy and Materials 2009年第5期16卷 534-539页

作者： t.A.daniel Sagayaraj S.Suresh M.Chandrasekar Department of Mechanical Engineering National Institute of Technology Tiruchirappalli-620015Tamil NaduIndia

the experimental investigations on the effect of the fly ash particle size, velocity, impingement angle, and feed rate were done with an emphasis on the effect of erosion on annealed SA 210 GrA1 （A） and normalized SA 210 GrA1 （N） carbon steel economizer-tube materials. Erosion rates were evaluated with different impingement angles ranging from 15° to 90°, at four different velocities of 32.5, 35, 37.5, and 40 m/s, and at four different feed rates of fly ash particles of 2, 4, 6 and 8 g/min. the erodent used was fly ash particles, sizes ranging from 50-250 μm of irregular shapes. Erosion rate is found to be the maximum at the impingement angle of 30°. Erosion rates of the carbon steel tube in different heat treatment conditions, annealed and normalized, at a constant velocity of 32.5 m/s with different angles were studied. In all cases of feed rates, impingement angles, particle sizes, and velocities of fly ash particles, it has been found that the erosion rate of the annealed tube is less than that of the normalized tube. Empirical correlations for erosion rate relating the velocity, size, feed rate, and impingement angle of the particles and elongation property of the target materials were arrived. Morphologies of the eroded surface were examined by scanning electron microscope （SEM）.

关键词： erosion rate economiser tubes annealing normalizing

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