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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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An interferometric ex vivo study of corneal biomechanics under physiologically representative loading,highlighting the role of the limbus in pressure compensation

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Eye and Vision 2020年第5期7卷 412-422页

作者： Abby Wilson john Jones john RTyrer john marshall Wolfson School of Mechanical Manufacturing and Electrical EngineeringLoughborough UniversityLoughboroughUK Laser Optical Engineering Ltd. DerbyshireUK Institute of Ophthalmology UCLLondonUK

Background:The mechanical properties of the cornea are complex and regionally *** paper uses an original method to investigate the biomechanics of the cornea in response to hydrostatic loading over the typical physiological range of intra-ocular pressure(IOP)fluctuations thereby increasing understanding of clinically relevant corneal biomechanical properties and their contributions to the refractive properties of the ***:Displacement speckle pattern interferometry(DSPI)was used to measure the total surface displacement of 40 porcine and 6 human corneal-scleral specimens in response to pressure variations up to 1 mmHg from a baseline of 16.5 *** specimens were mounted in a modified artificial anterior chamber(AAC)and loaded *** of high strain in response to loading were identified by comparing the displacements across different ***:The nature of the response of the corneal surface to loading demonstrated high regional topographic *** properties were shown to be asymmetrical,and deformation of the limbal and pre-limbal regions dominated these responses respectively with over 90%(N-T)and 60%(S-I)of the total maximum displacement occurring in these regions indicating *** contrast,the curvature of the central cornea remained relatively unchanged merely translating in ***:The limbal and pre-limbal regions of the cornea appear to be fundamental to the absorption of small pressure fluctuations facilitating the curvature of the central cornea to remain relatively *** differential mechanical properties of this region could have important implications for the application of corneal surgery and corneal crosslinking,warranting further investigation.

关键词： Cornea Biomechanics Interferometry Limbus Topography

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Sub-dissociative dose ketamine administration for managing pain in the emergency department

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World Journal of Emergency Medicine 2018年第4期9卷 249-255页

作者： Sergey Motov Jefferson Drapkin Antonios Likourezos Joshua Doros Ralph Monfort john marshall Department of Emergency Medicine Maimonides Medical Center

BACKGROUND： We describe our experience of utilizing sub-dissociative dose ketamine （SDK） in managing a variety of acute and chronic painful conditions in the emergency department （ED）. METHODS： A descriptive study was conducted in our ED over a period of seven years （2010-2016） by retrospectively reviewing charts of patients aged 18 and older presenting to the ED with painful complaints and receiving SDK analgesia. Primary data analyses included type of SDK administration （intravenous push [IVP], short-infusion [SI] or continuous infusion [CI]）, dosing, rates of analgesic utilization before and after SDK administration, and adverse effects. RESULTS： Three hundred sixty-two patients were enrolled in the study. Mean ketamine doses given by IVP, St and CI were 26.3 rag, 23.4 rag, and 11.3 rag. The mean duration of CI was 135.87 minutes. The percentage of patients not requiring post-SDK analgesia increased by 16%, 18%, and 37% in IVP, SI and CI groups. Adverse effects were recorded for 13% of patients. CONCLUSION： SDK administered by IVP, SI, and CI in the ED for a variety of painful conditions is a feasible analgesic modality in the ED that is associated with a decrease in overall requirements of post-ketamine analgesia and opioid sparing.

关键词： Ketamine Analgesia Emergency department Sub-dissociative Infusion

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Post-infectious irritable bowel syndrome

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World Journal of Gastroenterology 2009年第29期15卷 3591-3596页

作者： Marroon Thabane john K marshall Division of Gastro-enterology McMaster University Medical Centre Hamilton Ontario L8N 3Z5 Canada Farncombe Family Digestive Health Research Institute McMaster University Hamilton Ontario L8N 3Z5 Canada Department of Clinical Epidemiology and Biostatistics McMaster University Hamilton Ontario L8N 3Z5 Canada

Post-infectious irritable bowel syndrome (PI-IBS) is a common disorder wherein symptoms of IBS begin after an episode of acute gastroenteritis. Published studies have reported incidence of PI-IBS to range between 5% and 32%. The mechanisms underlying the development of PI-IBS are not fully understood, but are believed to include persistent sub-clinical inflammation, changes in intestinal permeability and alteration of gut flora. Individual studies have suggested that risk factors for PI-IBS include patients' demographics, psychological disorders and the severity of enteric illness. However, PI-IBS remains a diagnosis of exclusion with no specific disease markers and, to date, no definitive therapy exists. The prognosis of PIIBS appears favorable with spontaneous and gradual resolution of symptoms in most patients.

关键词： Irritable bowel syndrome Functionacolonic disease Gastroenteritis Functional bowedisorder

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PROWESS-Shock:activated protein C in septic shock

PROWESS-Shock:activated protein C in septic shock

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国际全身性感染论坛-2011北京

作者： john marshall St Michaels Hospital TorontoOntarioCanada

＜正＞The history of the development of effective adjuvant treatments for sepsis has been a frustrating one. Numerous interventions have shown promise in early phase clinical research,only to fail to show a sufficiently robust mortality benefit in phase III trials to achieve regulatory *** exception to this sorry narrative was the PROWESS study of recombinant

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Recent mechanisms of laser therapy:Refractive,new vascularization ascularization and Glaucoma

Recent mechanisms of laser therapy:Refractive,new vasculariz...

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中华医学会第十二届全国眼科学术大会

作者： john marshall KCL Department of Ophthalmdogy The Rayne InstituteSt．Thomas’ Hospital

The number of surgical lasers used in world has grown remarkably in the past few *** with this proliferation is the increasing requirement for understanding of both the diversity of applications of surgi- cal lasers a...

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World Journal of Gastrointestinal Oncology 2013年第11期5卷 198-203页

作者： Osama E Rahma Mauricio Burotto Luisa Matos Do Canto Alexandre A Germanos Bassem R Haddad john L marshall Medical Oncology Branch National Cancer Institute the Lombardi Comprehensive Cancer Center Georgetown University Medical Center Whitman College the Ruesch Center for the Cure of GI Cancers Georgetown University Medical Center

We are reporting the longest disease-free interval ever published for colorectal cancer, using gene profiling to confirm the linkage of the primary and metastasis. This rare case reports on a patient with late recurrence of colorectal cancer in the lung 19 years after its initial diagnosis. We used high-resolution array CGH(aCGH) to analyze the genetic aberrations of both the primary rectal and the recurrent metastatic lung lesions. Interestingly, we found striking similarities between the two lesions, despite the 19 years disease-free *** addition, most of the genes that were previously reported to be associated with a high recurrence score showed copy number gains by aCGH in one or both lesions. Our findings suggest that aCGH may be a helpful tool in analyzing the origin of metastatic lesions and reflect the need for a better understanding of the characteristics of the rectal tumors with a late recurrence potential.

关键词： Colorectal cancer Genetic aberrations Delayed Recurrence High-resolution array CGH

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多脏器功能衰竭计分:危重病器官功能衰竭严重程度与后果的相关关系

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中国危重病急救医学 1989年第1期1卷 56-57,53页

作者： john marshall 周杰

第5届世界危重病急救医学学术交流会,于1989年9月3日至8日在日本东京都召开。大会共交流学术论文1200余篇。反映了四年来世界各国危重病急救医学的成果及进展。本刊结合各期重点,将有关资料以摘要形式介绍给广大读者,供参考。本期刊登... 详细信息

第5届世界危重病急救医学学术交流会,于1989年9月3日至8日在日本东京都召开。大会共交流学术论文1200余篇。反映了四年来世界各国危重病急救医学的成果及进展。本刊结合各期重点,将有关资料以摘要形式介绍给广大读者,供参考。本期刊登有关感染性多系统脏器功能衰竭文摘17篇,统一由天津市急救医学研究所崔乃杰主任医师审校。

关键词：危重病急救摘要形式学术论文学术交流急救医学感染性日至日本东京都心血管系统危重病人

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Management of Severe Pancreatitis

Management of Severe Pancreatitis

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中国重症医学的创新与发展——第二届中国医师协会重症医学医师分会暨第九届中国病理生理学会危重病医学专业委员会2010年危重病医学全国会议

作者： john C.marshall MD FRCSC

The ICU management of patients with severe necrotizing pancreatitis has changed over the last 10 to 20 years. Prior to this time,the mortality associated with necrotizing pancreatitis was prohibitive,currently upwards of 75 to 85%of patients survive and return to a normal premorbid quality of *** success has been accomplished by adherence to a few basic principles.

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Basic Biology for the Clinician

Basic Biology for the Clinician

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中国重症医学的创新与发展——第二届中国医师协会重症医学医师分会暨第九届中国病理生理学会危重病医学专业委员会2010年危重病医学全国会议

作者： john C.marshall MD FRCSC

Sepsis is an enormously complex biologic process that involves the integrated interaction of microbial products with literally thousands of differing host - based *** the past four decades,an enormous amount has been learned about how this process occurs at the level of the cell;this information will inform the development and use of new *** the details are complicated,and still emerging,some basic principles are now appar- ent.

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