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

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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

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

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

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

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

A test of the species confidence hypothesis in dusky damselfish

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Current Zoology 2024年第1期70卷 79-86页

作者： Elle Overs Sydney Stump Isabel Severino daniel t.Blumstein Department of Ecology and Evolutionary Biology University of CaliforniaLos AngelesCA 90095-1606USA

Visual cues are important in both interspecific and intraspecific *** species confidence hypothesis proposes that animals are more attracted to conspecific colors and repelled by colors,not on their *** on terrestrial lizards and birds have tested the species confidence hypothesis and shown that conspecific colors elicit reduced antipredator *** date,the species confidence hypothesis has not been tested in the marine environment,specifically on coral reefs where color communication is of vital *** addressed this knowledge gap by measuring flight initiation distance(the distance an individual moves away from an approaching threat)in dusky damselfish(Stegastes nigricans)in response to an approaching disc of 1 of 4 different color treatments:conspecific,blue,yellow,and *** the species confidence hypothesis explained variation in damselfish flight initiation distance,then we expected individuals to tolerate closer approaches when approached by a conspecific *** addition,we calculated the color difference between each stimulus and its corresponding back-ground as a potential alternative explanation for flight *** tolerated the closest approach from the conspecific color stimulus;there were no significant differences between other colors and there was no support for the alternative color difference *** with similar terrestrial studies,these results are relevant to ecotourists'choice of swimsuit and wetsuit colors because color choice may modify naturalantipredatorbehavior.

关键词： antipredator behavior flight initiation distance risk assessment species confidence hypothesis Stegastes nigricans

Beyond the code:the role of histone methylation in cancer resistance and therapy

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Signal transduction and targeted therapy 2024年第7期9卷 2837-2839页

作者： daniel Noerenberg Frederik Damm Charité–Universitätsmedizin Berlin corporate member of Freie Universität BerlinHumboldt Universität zu Berlinand Berlin Institute of HealthDepartment of HematologyOncologyand Cancer ImmunologyBerlinGermany German Cancer Consortium(Deutsches Konsortium für translationale Krebsforschung DKTK)Partner SiteBerlinGermany

In a recently published paper in Nature,Yamagishi et *** a comprehensive exploration on the mechanistic basis and subsequent emergence of resistance of targeting histone H3 lysine trimethylation(H3K27me3)using the EZH... 详细信息

关键词： EZH2 resistance

Elevation transition of aquatic insects closely matches a thermal feature in the Yungas of Northwestern Argentina

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Journal of Mountain Science 2024年第2期21卷 433-448页

作者： Alexandra BUItRAGO-GUACANAME Carlos MOLINERI Andrés LIRA-NORIEGA daniel Andrés DOS SANtOS Neotropical Biodiversity Institute(CONICEt-UNt) UNT-DomesHorco Molle S/N4107 TucumánArgentina CONACYt Research Fellow Network of Advanced Molecular StudiesInstitute of Ecology A.COld Road to Coatepec 351El HayaCP 91073XalapaVeracruzMexico Biostatistics Chair Faculty of Natural Sciences and IMLNational University of TucumánSan Miguel de TucumánMiguel Lillo 2054000 TucumánArgentina

temperature is a key factor that shapes the distribution of *** knowledge about how species respond to temperature is relevant to devise strategies for addressing the impacts of climate *** insects are particularly vulnerable to climate change,yet there is still much to learn about their ecology and *** the Yungas ecoregion of Northwestern Argentina,cold-and warm-adapted species of the orders Ephemeroptera,Plecoptera,and trichoptera(EPt)are segregated by *** modeled the ecological niche of South American EPt species in this region using available data and projected their potential distribution in geographic *** were grouped based on their ecogeographic similarity,and we analyzed their replacement pattern along elevation gradients,focusing on the ecotone where opposing thermal preferences *** this interface,we identified critical points where the combined incidence of cold and warm assemblages maximizes,indicating a significant transition *** found that the Montane Cloud Forest holds the interface,with a particularly greater suitability at its lower *** main axis of the interface runs in a N-S direction and falls between 14°C-16°C mean annual *** probability of a particular location within a basin being classified as part of the interface increases as Kira’s warmth index approaches a score around *** the interface is critical for defining the thermal limits of species distribution and designing biomonitoring *** in the location of thermal constants related to mountainous ecotones may cause vertical displacement of aquatic insects and vegetation *** have recognized significant temperature thresholds that serve as indicators of suitability for the *** global warming is anticipated to shift these indicators,we suggest using them to monitor the imprints of climate change on mountain ecosystems.

关键词： Austral Yungas Ecological Niche Model Ephemeroptera Kira’s warmth index Plecoptera trichoptera

the Silk roads: phylogeography of Central Asian dice snakes (Serpentes: Natricidae) shaped by rivers in deserts and mountain valleys

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Current Zoology 2024年第2期70卷 150-162页

作者： daniel Jablonski Konrad Mebert Rafaqat Masroor Evgeniy Simonov Oleg Kukushkin timur Abduraupov Sylvia Hofmann Department of Zoology Comenius University in BratislavaBratislavaSlovakia Global Biology BirrSwitzerland Pakistan Museum of Natural History ShakarparianIslamabadPakistan Severtsov Institute of Ecology and Evolution Russian Academy of SciencesMoscowRussia t.I.Vyazemski Karadag Scientific Station-Nature Reserve—Branch of A.0.Kovalevsky Institute of Biology of the Southern Seas TheodosiaCrimea Zoological Institute of the RAS Saint PetersbourgRussia Institute of Zoology Academy of Sciences of the Republic of UzbekistanYunusabadTashkentUzbekistan Museum Koenig Bonn LIBLeibniz Institute for the Analysis of Biodiversity ChangeBonnGermany UFZ-Helmholtz Centre for Environmental Research Department of Conservation BiologyPermoserstrasse 1504318 LeipzigGermany

Influenced by rapid changes in climate and landscape features since the Miocene,widely distributed species provide suitable models to study the environmental impact on their evolution and current genetic *** dice snake Natrix tessellata,widely distributed in the Western Palearctic is one such *** aimed to resolve a detailed phylogeography of *** with a focus on the Central Asian clade with 4 and the Anatolia clade with 3 mitochondrial lineages,trace their origin,and correlate the environmental changes that affected their distribution through *** expected time of divergence of both clades began at 3.7 Mya in the Pliocene,reaching lineage differentiation approximately 1 million years *** genetic diversity in both clades is rich,suggesting different ancestral areas,glacial refugia,demographic changes,and colonization *** Caspian lineage is the most widespread lineage in Central Asia,distributed around the Caspian Sea and reaching the foothills of the Hindu Kush Mountains in Afghanistan,and Eastern European lowlands in the *** distribution is limited by deserts,moun-tains,and cold steppe ***,Kazakhstan and Uzbekistan lineages followed the Amu Darya and the Syr Darya water systems in Central Asia,with ranges delimited by the large Kyzylkum and Karakum *** the western side,there are several lineages within the Anatolia clade that converged in the central part of the peninsula with 2 being endemic to Western *** distribution of both main clades was affected by expansion from their Pleistocene glacial refugia around the Caspian Sea and in the valleys of Central Asia as well as by environmental changes,mostly through aridification.

关键词： biogeography colonization Eurasia genetic diversity mitochondrial DNA Paratethys refugia water snakes.