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Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis

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Translational Neurodegeneration 2022年第1期11卷 707-717页

作者： Akram Zamani Adam K.Walker Ben Rollo Katie L.Ayers Raysha Farah terence j.o’brien David K.Wright Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneVIC 3004Australia Queensland Brain Institute The University of QueenslandSt LuciaQLD 4072Australia The Murdoch Children’s Research Institute The Royal Children’s HospitalParkvilleVIC 3052Australia Department of Pediatrics The University of MelbourneParkvilleVIC 3052Australia Department of Medicine The Royal Melbourne HospitalThe University of MelbourneParkvilleVIC 3052Australia

Background: Multiple lines of evidence suggest possible impairment of the glymphatic system in amyotrophic lateral sclerosis (ALS). To investigate this, we used in vivo magnetic resonance imaging (MRI) to assess glymphatic func-tion early in the course of disease in a transgenic mouse with doxycycline (Dox)-controlled expression of cytoplasmic human TDP-43 (hTDP-43ΔNLS), mimicking the key pathology implicated in ALS. Methods: Adult TDP-43 transgenic and littermate monogenic control mice underwent longitudinal multimodal MRI one and three weeks after the cessation of Dox feed, together with weekly rotarod assessments of motor per-formance. Glymphatic function was assessed using dynamic contrast-enhanced MRI to track the clearance of an MR contrast agent injected into the cisterna magna. Results: Compared to their littermate controls, TDP-43 mice exhibited progressive neurodegeneration including that within the primary motor cortex, primary somatosensory cortex and corticospinal tract, significant weight loss includ-ing gastrocnemius atrophy, and shortened telomere length. Furthermore, in the presence of this ALS-like phenotype, these mice have significantly disrupted glymphatic function. Conclusions: Although the relationship between glymphatic clearance and ALS disease progression remains to be elucidated, these changes occurred very early in the disease course. This provides initial evidence to suggest that the glymphatic system might be a potential therapeutic target in the treatment of ALS.

关键词： Magnetic resonance imaging Diffusion-weighted imaging Neurodegeneration Cerebrospinal fluid Telomere

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Practical considerations of dietary therapies for epilepsy in adults

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Acta Epileptologica 2021年第1期3卷 101-107页

作者： Neha Kaul john-Paul Nicolo terence j.o’brien Patrick Kwan Department of Nutrition and Dietetics Alfred Hospital55 Commercial RoadMelbourneVIC 3004Australia Department of Allied Health(Clinical Nutrition) Royal Melbourne HospitalParkvilleAustralia Departments of Neurosciences and Neurology Alfred Hospital and Monash UniversityMelbourneAustralia Departments of Medicine and Neurology Royal Melbourne HospitalUniversity of MelbourneMelbourneAustralia Chongqing Key Laboratory of Neurology The First Affiliated HospitalChongqing Medical UniversityChongqingChina

Despite the increasing number of anti-seizure medications becoming available,the proportion of patients with drug-resistant epilepsy remains *** therapy for epilepsy is well-established practice in paediatric care,but relatively underutilised in ***,international recommendations have been published to guide the treatment of adults receiving dietary therapy for *** review focuses on the specific aspects of care unique to the management of adults receiving dietary therapy for epilepsy,including patient selection,diet composition,initiation,monitoring and cessation of dietary *** emphasise the need for a multidisciplinary team approach with appropriately trained neurologists and dietitians to provide holistic care while the patients are receiving dietary *** research should focus on the optimal diet composition and meeting the psychosocial needs of adults with epilepsy to maximise efficacy and adherence to dietary treatment.

关键词： Ketogenic diet Epilepsy Diet Drug-resistant epilepsy Nutrition

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Neurological heterotopic ossification:novel mechanisms,prognostic biomarkers and prophylactic therapies

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Bone Research 2020年第4期8卷 379-392页

作者： Ker Rui Wong Richelle Mychasiuk terence j.o’brien Sandy R.Shultz Stuart j.McDonald Rhys D.Brady Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneVICAustralia Department of Medicine Royal Melbourne HospitalThe University of MelbourneParkvilleVICAustralia Department of Physiology Anatomy and MicrobiologySchool of Life SciencesLa Trobe UniversityBundooraVICAustralia

Neurological heterotopic ossification(NHo)is a debilitating condition where bone forms in soft tissue,such as muscle surrounding the hip and knee,following an injury to the brain or spinal *** abnormal formation of bone can result in nerve impingement,pain,contractures and impaired *** are often diagnosed with NHo after the bone tissue has completely mineralised,leaving invasive surgical resection the only remaining treatment *** resection of NHo creates potential for added complications,particularly in patients with concomitant injury to the central nervous system(CNS).Although recent work has begun to shed light on the physiological mechanisms involved in NHo,there remains a significant knowledge gap related to the prognostic biomarkers and prophylactic treatments which are necessary to prevent NHo and optimise patient *** article reviews the current understanding pertaining to NHo epidemiology,pathobiology,biomarkers and treatment *** particular,we focus on how concomitant CNS injury may drive ectopic bone formation and discuss considerations for treating polytrauma patients with *** conclude that understanding of the pathogenesis of NHo is rapidly advancing,and as such,there is the strong potential for future research to unearth methods capable of identifying patients likely to develop NHo,and targeted treatments to prevent its manifestation.

关键词： such has likely

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丘脑局部注射药物的方法验证

丘脑局部注射药物的方法验证

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第十二次全国中西医结合儿科学术会议

作者：刘力戈 Rink-jan Lohmana Margaret Morris terence j.o’brien 首都医科大学附属北京友谊医院墨尔本大学药理系

1．简介药物、神经递质、细胞因子等在中枢神经系统不同的区域或神经细胞核中,根据受体的类型和数量的不同,可能发挥着完全不同的作用。在药理研究中,为了研究药物对中枢神经系统的影响, 常常采用把药物直接注射到实验动物脑室系统的方... 详细信息

1．简介药物、神经递质、细胞因子等在中枢神经系统不同的区域或神经细胞核中,根据受体的类型和数量的不同,可能发挥着完全不同的作用。在药理研究中,为了研究药物对中枢神经系统的影响, 常常采用把药物直接注射到实验动物脑室系统的方法。这种方法是以脑脊液作为循环载体,注射的药物先通过血脑屏障再作用于全脑和脊髓而发挥作用。然而,脑室注射无法区分注射药物对独立神

关键词：小儿癫痫药物治疗局部注射

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CircTUBD1: A Novel Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis

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journal of Clinical and Translational Hepatology 2022年第4期10卷 571-573页

作者： Catherine Yujia Gu terence Kin Wah Lee Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic UniversityHong KongChina State Key Laboratory of Chemical Biology and Drug Discovery The Hong Kong Polytechnic UniversityHong KongChina

Citation of this article:Gu CY,Lee ***1:A Nov-el Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis.j Clin Transl Hepatol 2022;10(4):***:10.14218/*** liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer mortality worldwide.1 Liver transplantation and surgical resection are two curative therapeutic options for liver cancer patients at the early ***,most patients are diagnosed at advanced stages.

关键词： Liver Therapeutic cancer

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Advancing pressure sensors performance through a flexible MXene embedded interlocking structure in a microlens array

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Nano Research 2023年第7期16卷 10493-10499页

作者： Tong Li Zhenzong Xu Ben Bin Xu Zhanhu Guo Yunhong jiang Xuehua Zhang Maryam Bayati terence Xiaoteng Liu Yan-Hua Liu School of optoelectronic Science and Engineering Key Lab of Advanced Optical Manufacturing Technologies of Jiangsu Province&Key Lab of Modern Optical Technologies of Education Ministry of ChinaSoochow UniversitySuzhou 215006China Department of Mechanical and Construction Engineering Faculty of Engineering and EnvironmentNorthumbria UniversityNewcastle upon TyneNE18STUK Hub for Biotechnology in the Built Environment Department of Applied SciencesNorthumbria University at NewcastleNE18STUK Department of Chemical and Materials Engineering University of AlbertaEdmontonAlberta T6G 1H9Canada

Piezoresistive composite elastomers have shown great potentials for wearable and flexible electronic applications due to their high sensitivity,excellent frequency response,and easy signal detection.A composition membrane sensor with an interlocked structure has been developed and demonstrated outstanding pressure sensitivity,fast response time,and low temperature drift *** with a flexible MXene-based flat sensor(Ti_(3)C_(2)),the interlocked sensor exhibits a significantly improved pressure sensitivity of two magnitudes higher(21.04 kPa^(-1)),a fast reaction speed of 31 ms,and an excellent cycle life of 5000 test *** viability of sensor in responding to various external stimuli with high deformation capacity has been confirmed by calculating the force distribution of a polydimethylsiloxane(PDMS)film model with a microlens structure using the solid mechanics module in *** conventional process,we utilized three-dimensional(3D)laser-direct writing lithography equipment to directly transform high-precision 3D data into a micro-nano structure morphology through variable exposure doses,which reduces the hot melting ***,the flexible pressure device is capable of detecting and distinguishing signals ranging from finger movements to human pulses,even for speech *** simple,convenient,and large-format lithographic method offers new opportunities for developing novel human-computer interaction devices.

关键词： three-dimensional(3D)lithography microlens array flexible electronics pizoresistive pressure sensors MXene

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Expert elicitations of smallholder agroforestry practices in Seychelles:A SWoT-AHP analysis

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区域可持续发展(英文) 2023年第3期4卷 282-295页

作者： Daniel EToNGo Uvicka BRISToL terence Epule EPULE Ajith BANDARA Sandra SINoN james Michel Blue Economy Research Institute University of SeychellesAnse Royale1348Seychelles Department of Environmental Sciences University of SeychellesAnse Royale1348Seychelles International Water Research Institute Mohammed VI University PolytechnicBen Guerir43150Morocco Agrifood research and development unit University of Quebec in Abitibi-Témiscamingue(UQAT)QuebecJ0Z 3B0Canada Department of Computing and Information Systems University of SeychellesAnse Royal1348Seychelles Department of Agriculture Ministry of AgricultureClimate Change and Environment(MACCE)Victoria445Seychelles

Agroforestry can leverage the co-benefits of climate change adaptation and mitigation while conserving biodiversity and restoring degraded and deforested *** preference of relevant stakeholders regarding agroforestry practices enhances sustainable land management through strategic decision-making in Seychelles and other island states.A suitable approach for assessing stakeholders'preferences of agroforestry is the implementation of the strengths,weaknesses,opportunities,and threats(SWoT)approach in combination with the analytic hierarchy process(AHP)*** entry point of this study is an extensive literature review process,during which 28 SWoT factors were *** SWoT factors were deliberated on during a half-day workshop with agricultural experts who agreed on 20 SWoT factors that reflect the local realities of the Seychelles through a consensus *** the SWoT-AHP approach,focus group discussions were conducted to examine the perceptions of researchers and extension workers about the adoption of agroforestry in *** results indicated that the positive aspects of smallholder agroforestry outweigh the negative *** example,increased agricultural production,control runoff and soil erosion receive the highest scores among the strength factors perceived by researchers and extension workers,*** willingness of international organizations to fund agroforestry-related projects and the existence of native tree species on farmlands have the highest scores among the opportunity *** lack of education,information,and communication between the government and farmers,and the small land size and crop competition have the highest scores among the weakness ***,change in government policies on land use has the highest score among the threat factors by researchers,whereas the most significant threat is climate change and variability for the extension *** provision for a 30-year land lease agreement in

关键词： Smallholder farmers Agroforestry Climate resilience Extension worker Strengths weaknesses opportunities and threats(SWoT) Analytic hierarchy process(AHP) Seychelles

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The wow factor as a determinant of funding for disorders of the skin

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journal of Medical Colleges of PLA(China) 2015年第2期30卷 61-68页

作者： terence j.Ryan Green Templeton College oxford University Oxford OX 26 HG UK

As people live beyond 100 years, there is an extended period of impaired quality of life for the increasing numbers of individuals with skin disorders. There is also a growing work force of fit elderly individuals who are able to provide low technology skin care and who can teach self-help if well instructed. The International Society of Dermatology's sub-committee Skin Care for All: Community Dermatology seeks to bring together those who care for skin diseases and those who manage wounds, burns, lymphoedema and neglected tropical diseases affecting the skin for the purpose of skin care. Their focus is the repair of four functions: barrier, thermoregulation, sensory perception and communication. The curriculum includes low cost self-help and the restoration of absent skin. The care expectation is one of technical proficiency integrated with kindness and altruism. The concept is attracting wide attention but needs to develop compelling and persuasive arguments("wow factors") regarding why it should be funded. There is probably no greater wow factor than tracing the path of a severely injured patient from the battlefield through the course of immediate first aid by paramedics to the surgeon in the frontline tent who can almost guarantee survival. Seeing these disfigured persons winning trophies at the olympic Games has garnered the admiration of millions of viewers.

关键词： Skin disorders Wound healing Skin care

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Generalized polyspike train:an EEG biomarker of drug-resistant idiopathic generalized epilepsy

Generalized polyspike train:an EEG biomarker of drug-resista...

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第六届CAAE脑电图与神经电生理大会

作者： Yanping Sun Udaya Seneviratne Piero Perucca Zhibin Chen Kee Meng Tan terence j.o' brien Wendyl D' Souza Patrick Kwan The Affiliated Hospital of Qingdao University The Royal Melbourne Hospital The University of Melbourne St.Vincent's Hospital Melbourne The University of Melbourne The School of Clinical Sciences at Monash Health Monash University The Alfred Hospital The Central Clinical School Monash University

objective:To identifyclinical and EEG biomarkers of drug resistance in adults With idiopathic generalized epilepsy(IGE).Methods:We conducted a case-control study consisting of a discovery cohort and a replication cohort independently assessed at two different *** each centre patients with IGE phenotype and generalized spike-wave discharges on EEG were classified as drug-resistant or *** changes were classified

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Thermal convection in ice sheets: New data, new tests

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Natural Science 2012年第7期4卷 409-418页

作者： terence j. Hughes Emeritus of Earth Sciences and Climate Change University of Maine 404 North Sixth Street Fort Pierre South Dakota 57532 USA

Thermal convection in the Antarctic Ice Sheet was proposed in 1970. Demonstrating its existence proved to be elusive. In 2009, tributaries to ice streams were postulated as the surface expression of underlying thermal convection rolls aligned in directions of advective ice flow. Two definitive tests of this hypothesis are now possible, using highly accurate ice elevations and velocities provided by the European, japanese, and Canadian Space Agencies that allow icestream tributaries and their velocities to be mapped. These tests are 1) measuring lowering of tributary surfaces to see if lowering is due only to advective ice thinning, or also requires lowering en masse in the broad descending part of convective flow, and 2) measuring transverse surface ice velocities to see if ice entering tributaries from the sides increases while crossing lateral shear zones, as would be required if this flow is augmented by convective flow ascending in the narrow side shear zones and diverted into tributaries by advective ice flow. If (1) and (2) are applied to tributaries converging on Byrd Glacier, the same measurements can be conducted when tributaries pack together to become “flow stripes” down Byrd Glacier and onto the Ross Ice Shelf to see if (2) is reduced when lateral advection stops. This could determine if thermal convection remains active or shuts down as ice thins. Thermal convection in the Antarctic Ice Sheet would raise three questions. Can it cause the ice sheet to self-destruct as convective flow turns on and off? Does it render invalid climate records extracted at depth from ice cores? Can the ice sheet be studied as a miniature mantle analogous in some respects to Earth’s mantle?

关键词： Thermal Convection Antarctic Ice Sheet Climate Change Rising Sea Level

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