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The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke:a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches

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Neural Regeneration Research 2021年第4期16卷 605-613页

作者： Magdalini Tsintou Kyriakos Dalamagkas tara lMoore Yogesh Rathi Marek Kubicki Douglas lRosene Nikos Makris Departments of Psychiatry and Neurology Services Center for Neural Systems InvestigationsCenter for Morphometric AnalysisAthinoula A.Martinos Center for Biomedical ImagingMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Department of Psychiatry Psychiatry Neuroimaging LaboratoryBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA University College of london Division of Surgery&Interventional Science Center for Nanotechnology&Regenerative MedicineUniversity College LondonLondonUK Department of Physical Medicine and Rehabilitation The University of Texas Health Science Center at HoustonHoustonTXUSA The Institute for Rehabilitation and Research Memorial Hermann Research Center The Institute for Rehabilitation and Research Memorial Hermann HospitalHoustonTXUSA Department of Anatomy&Neurobiology Boston University School of MedicineBostonMAUSA

Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)*** is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNS therapeutics *** the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury *** vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell *** the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative *** review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable *** rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the *** sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration ***,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of m

关键词： cortical injury exosomes extracellular vesicles hydrogels neural tissue engineering neural tissue repair neuroregeneration non-human primates stroke

Test-Retest Reliability of Functional Magnetic Resonance Imaging Activation for a Vergence Eye Movement Task

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Neuroscience Bulletin 2020年第5期36卷 506-518页

作者： Cristian Morales Suril Gohel Xiaobo li Mitchell Scheiman Bharat B.Biswal Elio M.Santos Chang Yaramothu tara l.Alvarez Biomedical Engineering New Jersey Institute of TechnologyNewarkNJ 07102USA Pennsylvania College of Optometry Salus UniversityPhiladelphiaPA 19027USA Department of Health Informatics Rutgers University School of Health ProfessionsNewarkNJ 07107USA

Vergence eye movements are the inward and outward rotation of the eyes responsible for binocular *** studies have mapped and investigated the neural substrates of vergence,it is not well understood whether vergence eye movements evoke the blood oxygen level-dependent signal reliably in separate experimental *** test-retest reliability of stimulus-induced vergence eye movement tasks during a functional magnetic resonance imaging(fMRI)experiment is important for future randomized clinical trials(RCTs).In this study,we established region of interest(ROI)masks for the vergence neural ***-seven binocularly normal young adults participated in two functional imaging sessions measured on different days on the same 3 T Siemens *** fMRI experiments used a block design of sustained visual fixation and rest blocks interleaved between task blocks that stimulated eight or four vergence eye *** test-retest reliability of task-activation was assessed using the intraclass correlation coefficient(ICC),and that of spatial extent was assessed using the Dice *** activation during the vergence eye movement task of eight movements compared to rest was repeatable within the primary visual cortex(ICC=0.8),parietal eye fields(ICC=0.6),supplementary eye field(ICC=0.5),frontal eye fields(ICC=0.5),and oculomotor vermis(ICC=0.6).The results demonstrate significant test-retest reliability in the ROIs of the vergence neural substrates for functional activation magnitude and spatial extent using the stimulus protocol of a task block stimulating eight vergence eye movements compared to sustained *** ROIs can be used in future longitudinal RCTs to study patient populations with vergence dysfunctions.

关键词： Vergence eye movement Test-retest reliability Functional MRI Vergence region of interest masks

Ten misconceptions regarding decision-making in critical care

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World Journal of Critical Care Medicine 2024年第2期13卷 72-82页

作者： tara Ramaswamy Jamie l Sparling Marvin G Chang Edward A Bittner Department of Anesthesiology Perioperative and Pain MedicineStanford University School of MedicineStanfordCA 94305United States Department of Anesthesia Critical Care and Pain MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States

Diagnostic errors are prevalent in critical care practice and are associated with patient harm and costs for providers and the healthcare *** complexity,illness severity,and the urgency in initiating proper treatment all contribute to decision-making ***-related factors such as fatigue,cognitive overload,and inexperience further interfere with effective *** science has provided insight into the clinical decision-making process that can be used to reduce *** evidence-based review discusses ten common misconceptions regarding critical care *** understanding how practitioners make clinical decisions and examining how errors occur,strategies may be developed and implemented to decrease errors in Decision-making and improve patient outcomes.

关键词： Clinical reasoning Cognitive bias Critical care Debiasing strategies decision making Diagnostic reasoning Diagnostic error Heuristics Medical knowledge Patient safety

Complications from Plaque versus Proton Beam Therapy for Choroidal Melanoma: A Qualitative Systematic Review

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Journal of Cancer Therapy 2016年第3期7卷 169-185页

作者： Victoria l. Tseng Anne l. Coleman Zuo-Feng Zhang tara A. McCannel Stein Eye Institute David Geffen School of Medicine at UCLA Los Angeles CA USA Department of Epidemiology UCLA Fielding School of Public Health Los Angeles CA USA

Plaque brachytherapy has been a mainstay of treatment for choroidal melanoma to achieve intraocular tumor control. The most common radioisotopes used for treating smaller sized tumors are Iodine-125 in North America and Ruthenium-106 in Europe. Proton beam radiotherapy is available at a few centers and may also be used to achieve local tumor control. Both plaque and proton beam therapy are known to be associated with a range of complications that may affect visual outcome and quality of life. These include radiation retinopathy, optic neuropathy, neovascular glaucoma and local treatment failure, requiring enucleation. While differences in the rates of these complications have not been well established in the literature for patients treated with plaque versus proton beam therapy for choroidal melanoma, certain geographic regions prefer one treatment modality over the other. The purpose of this qualitative systematic review was to compare and contrast reported complications that developed with plaque and proton beam therapy for the treatment of choroidal melanoma in studies published over a ten-year period. Reported rates suggest that patients with proton beam therapy had potentially higher rates of complications, including vision loss, enucleation, and neovascular glaucoma compared to those with plaque therapy. The rates of optic neuropathy, radiation retinopathy, and cataract formation were widely variable for the two treatment modalities and rates of metastasis and metastasis-free survival appeared similar with both treatments. The most common reported predictors of ocular complications following both types of therapy were tumor distance from the optic nerve, tumor thickness, and radiation dose, suggesting that inherent tumor characteristics play a role in visual prognosis.

关键词： Choroidal Melanoma Uveal Melanoma Plaque Therapy Brachytherapy Proton Therapy Treatment Complications Metastasis Enucleation

Yellow fever virus outbreak in Brazil under current and future climate

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Infectious Disease Modelling 2021年第1期6卷 664-677页

作者： tara Sadeghieh Jan M.Sargeant Amy l.Greer Olaf Berke Guillaume Dueymes Philippe Gachon Nicholas H.Ogden Victoria Ng Population Medicine University of GuelphGuelphOntarioCanada Centre for Public Health and Zoonoses Ontario Veterinary CollegeUniversity of GuelphGuelphOntarioCanada Public Health Risk Sciences Division National Microbiology LaboratoryPublic Health Agency of CanadaGuelphOntarioSt.HyacintheQuebecCanada ESCER(Etude et Simulation du Climata l’Echelle Regionale)Centre Universite du Quebec a MontrealQuebecCanada

Introduction:Yellow fever(YF)is primarily transmitted by Haemagogus species of *** climate change,mosquitoes and the pathogens that they carry are expected to develop faster,potentially impacting the case count and duration of YF *** aim of this study was to determine how YF virus outbreaks in Brazil may change under future climate,using ensemble simulations from regional climate models under RCP4.5 and RCP8.5 scenarios for three time periods:2011-2040(short-term),2041-2070(mid-term),and 2071-2100(long-term).Methods:A compartmental model was developed to fit the 2017/18 YF outbreak data in Brazil using least squares *** explore the impact of climate change,temperature-sensitive mosquito parameters were set to change over projected time periods using polynomial equations fitted to their relationship with temperature according to the average temperature for years 2011-2040,2041-2070,and 2071-2100 for climate change scenarios using RCP4.5 and RCP8.5,where RCP4.5/RCP8.5 corresponds to intermediate/high radiative forcing values and to moderate/higher warming trends.A sensitivity analysis was conducted to determine how the temperature-sensitive parameters impacted model results,and to determine how vaccination could play a role in reducing YF in ***:Yellow fever case projections for Brazil from the models varied when climate change scenarios were applied,including the peak clinical case incidence,cumulative clinical case incidence,time to peak incidence,and the outbreak ***,a decrease in YF cases and outbreak duration was *** the observed incidence in 2017/18 to the projected incidence in 2070-2100,for RCP4.5,the cumulative case incidence decreased from 184 to 161,and the outbreak duration decreased from 21 to 20 *** RCP8.5,the peak case incidence decreased from 184 to 147,and the outbreak duration decreased from 21 to 17 *** observed decrease was primarily due to temperature increasing

关键词： Yellow fever Mosquito-borne disease Climate change Infectious disease model Temperature

An Ultra-High Performance liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Vancomycin Requiring Only 2 μl of Rabbit Serum

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American Journal of Analytical Chemistry 2017年第9期8卷 553-563页

作者： Veronika Schmitt Andras Szeitz tara l.Klassen Urs O.Hafeli Faculty of Pharmaceutical Sciences The University of British ColumbiaVancouverCanada

A highly sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPlC-MS/MS) method was developed for the quantification of vancomycin (VAN) in low volumes of rabbit serum. For each analysis, 2 μl rabbit serum was precipitated with methanol that contained the internal standard teicoplanin (TEI). The supernatant was transferred into a 384 well-plate, diluted with water, covered with a pierceable silicone mat and 5 μl was analyzed in positive ionization mode. The UHPlC-MS/MS consisted of an Agilent 1290 Infinity UHPlC system connected to an AB Sciex QTrap®5500 hybrid linear ion-trap triple quadrupole mass spectrometer equipped with a Turbo Spray source. Chromatographic separation was achieved using a Waters Acquity UPlC BEH C18 (1.7 μm, 2.1 mm × 100 mm) column, a VanGuard (1.7 μm, 2.1 × 5 mm) guard column and a mobile phase of water and methanol both containing 5 mM ammonium acetate with 0.1% formic acid. VAN was quantified with multiple reaction monitoring using the transitions of m/z 725.5/144.2, and TEI was monitored at m/z 940.6/316.4. The accuracy, precision, linearity, range and lower limit of quantification (llOQ) were determined. The accuracy was ≤9.93% and the precision was ≤10.6%. The range was established as 0.1 to 40 μg·ml-1. The llOQ was 0.1 μg·ml-1 VAN requiring 2 μl of sample with an accuracy of -20.2% and precision of 8.39%. The method was applied successfully to determine the VAN concentrations in rabbit serum after the i.v. administration of VAN via implanted ear catheters.

关键词： Ultra-High Performance liquid Chromatography-Tandem Mass Spectrometry Vancomycin Rabbit Serum Pharmacokinetics

The Relationship of the Sapstreak Fungus, <i>Ceratocystis virescens</i>, to Sugar Maple Dieback and Decay in Northern Michigan

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American Journal of Plant Sciences 2013年第2期4卷 436-443页

作者： tara l. Bal Dana l. Richter Andrew J. Storer Martin F. Jurgensen School of Forest Resources and Environmental Science Michigan Technological University Houghton USA

Unusually high levels of dieback have recently been reported in sugar maple, Acer saccharum Marsh., in Upper Michigan, and a network of plots was established to determine the extent and factors associated with the dieback. A possible contributor to this dieback is sapstreak disease caused by Ceratocystis virescens (Davidson) Moreau. Unhealthy trees with considerable crown dieback were evaluated across the western Upper Peninsula, MI to determine the prevalence of the sapstreak fungus using a minimally destructive sampling technique. Approximately 8% of 90 trees sampled were sapstreak positive and approximately 10% of trees were positive at one site that had recently been harvested. While the high levels of maple dieback present in these forests appear not to be directly caused by widespread sapstreak disease, the occurrence of sapstreak may be significantly impacting trees at some locations. However, even when present on a low number of trees, the biointeraction of sapstreak and decay rates from other fungi could be important for future tree mortality and value to the forest industry. Therefore, the effect of two sapstreak fungal isolates on the amount of decay caused by two common maple white rot fungi, Trametes versicolor (l.:Fr.) Pilat. And Irpex lacteus (Fr.:Fr.) Fr. was tested in the laboratory. Sugar maple wood blocks were precolonized by two native isolates of C. virescens followed by inoculation and incubation with decay fungi. Mean percent weight loss of blocks by white rot decay fungi ranged from 39% to 55%, but decay rates were not significantly affected by the presence of the sapstreak fungus.

关键词： Sapstreak Disease Acer sacharrum Decay Rates Crown Dieback

Co-chaperoning of chlorophyll and carotenoid biosynthesis by ORANGE family proteins in plants

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Molecular Plant 2023年第6期16卷 1048-1065页

作者： Tianhu Sun Peng Wang Sombir Rao Xuesong Zhou Emalee Wrightstone Shan lu Hui Yuan Yong Yang tara Fish Theodore Thannhauser Jiping liu Michael Mazourek Bernhard Grimm li li Robert W.Holley Center for Agriculture and Health USDA-ARSCornell UniversityIthacaNY 14853USA Plant Breeding and Genetics Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853UA Department of Plant Physiology Institute of BiologyHumboldt-Universitat zu Berlin10115 BerlinGermany School of Biological Sciences The University of Hong KongPokfulam RoadHong Kong 999077China State Key laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjng 210023China

Chlorophylls and carotenoids are essential photosynthetic *** spatiotemporally coordinate the needs of chlorophylls and carotenoids for optimal photosynthesis and fitness in response to diverse environmental and developmental ***,how the biosynthesis pathways of these two pigments are coordinated,particularly at posttranslational level to allow rapid control,remains largely ***,we report that the highly conserved ORANGE(OR)family proteins coordinate both pathways via posttranslationally mediating the first committed enzyme in each *** demonstrate that OR family proteins physically interact with magnesium chelatase subunit I(CHlI)in chlorophyll biosynthesis pathway in addition to phytoene synthase(PSY)in carotenoid biosynthesis pathway and concurrently stabilize CHlI and PSY *** show that loss of OR genes hinders both chlorophyll and carotenoid biosynthesis,limits light-harvesting complex assembly,and impairs thylakoid grana stacking in *** of OR safeguards photosynthetic pigment biosynthesis and enhances thermotolerance in both Arabidopsis and tomato *** findings establish a novel mechanism by which plants coordinate chlorophyll and carotenoid biosynthesis and provide a potential genetic target to generate climate-resilient crops.

关键词： photosynthetic pigments chlorophylls carotenoids OR family proteins CHll PSY thermotolerance

liver-specific deletion of mechanistic target of rapamycin does not protect against acetaminophen-induced liver injury in mice

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liver Research 2021年第2期5卷 79-87页

作者： Hua Sun Hong-Min Ni Jennifer M.McCracken Jephte Y Akakpo Sam Fulte tara McKeen Hartmut Jaeschke Hua Wang Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsThe University of Kansas Medical CenterKansas CityKSUSA Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina

Background:Acetaminophen(APAP)overdose can cause liver injury and liver failure,which is one of the most common causes of drug-induced liver injury in the United *** activation of autophagy by inhibiting mechanistic target of rapamycin(mTOR)protects against APAP-induced liver injury likely via autophagic removal of APAP-adducts and damaged *** the present study,we aimed to investigate the role of genetic ablation of mTOR pathways in mouse liver in APAP-induced liver injury and liver repair/***:Albumin-Cre(Alb-Cre)mice,mTOR^(f/f) and Raptor^(f/f) mice(C57Bl/6J background)were crossbred to produce liver-specific mTOR knockout(l-mTOR KO,Alb Cret/-,mTOR^(f/f))and liver-specific Raptor KO(l-Raptor,Alb Cret/-,Raptor^(f/f))***-Cre littermates were used as wild-type(WT)*** mice were treated with APAP for various time points for up to 48 *** injury,cell proliferation,autophagy and mTOR activation were ***:We found that genetic deletion of neither Raptor,an important adaptor protein in mTOR complex 1,nor mTOR,in the mouse liver significantly protected against APAP-induced liver injury despite increased hepatic autophagic *** deletion of Raptor or mTOR in mouse livers did not affect APAP metabolism and APAP-induced c-Jun N-terminal kinase(JNK)activation,but slightly improved mouse survival likely due to increased hepatocyte ***:Our results indicate that genetic ablation of mTOR in mouse livers does not protect against APAP-induced liver injury but may slightly improve liver regeneration and mouse survival after APAP overdose.

关键词： Acetaminophen(APAP) Autophagy Hepatotoxicity liver injury liver regeneration Mechanistic target of rapamycin(mTOR) Regulatory associated protein of mTOR complex(Raptor)