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Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

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Neural Regeneration Research 2024年第2期19卷 355-359页

作者： courtney J.Rouse Victoria N.Jensen Coy D.Heldermon Lacerta Therapeutics AlachuaFLUSA University of Florida College of Medicine GainesvilleFLUSA

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for *** results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological *** treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢ***-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential *** group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy ***,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

关键词： adeno-associated virus central nervous system gene therapy heparan sulfate immune response mucopolysaccharidoses type IIIB N-acetyl-alpha-glucosaminidase newborn screening

The use of Montgomery salivary bypass tubes and pharyngocutaneous fistula following salvage laryngectomy

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 43-48页

作者： courtney B.Shires Mackenzie Latour Merry Sebelik Karuna Dewan West Cancer Center GermantownTennesseeUSA Department of Otolaryngology-Head and Neck Surgery Louisiana State University Health ShreveportShreveportLouisianaUSA Department of Otolaryngology-Head and Neck Surgery Emory UniversityAtlantaGeorgiaUSA

Objectives:Pharyngocutaneous fistula(PCF)is the most common complication to follow total laryngectomy(TL)and is associated with increases in length of hospital stay and with a need for revision surgery or readmission,as well as with delays in return to oral *** who require salvageTL(STL)or primary(chemo)radiation therapy are at higher risk for developing *** to the quality‐of‐life burden of PCF on patients,limiting this occurrence is ***:We conducted a retrospective cohort study of patients undergoing STL with placement of Montgomery salivary bypass tube(MSBT)^(TM)for at least 2 weeks duration between 2013 and 2017 at a single *** patients all underwent free flap *** primary outcome of interest was development of *** outcomes included demographics,previous treatment,base of tongue(BOT)involvement,extent of defect,concurrent neck dissection(ND),and margin ***χ^(2) analysis was used to evaluate factors associated with ***:Forty‐four patients underwent STL with Montgomery tube placement and free flap *** developed PCF(18.2%).The average age was 61.6 years;36 patients were male(81.8%),whereas eight patients were female(18.2%).There was no association between PCF and previous chemoradiation versus radiation(15.8%vs.33.3%,P<0.30),BOT involvement versus not(11.1 vs.22.2%,P<0.38),circumferential versus partial defect(18.8%vs.17.9%,P<0.94),ND versus none(10%vs.25%,P<0.20),or margin ***:PCF complicated 18.2%of STL cases at our institution and was not associated with differences in primary treatment modality,presence of concomitant ND,extent of pharyngeal defect,BOT involvement,or positive frozen or permanent surgical margin.

关键词： free flap reconstruction Montgomery pharyngocutaneous fistula salivary bypass tube salvage total laryngectomy total laryngectomy

秸秆-磷石膏联用对赤泥的腐殖质组分和微生物群落的影响

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Journal of Central South University 2024年第2期31卷 460-476页

作者：吴昊朱轩郅唐崇俭黄诗蔚孙伟江钧朱锋杨兴旺 RONAN courtney 薛生国 School of Metallurgy and Environment Central South UniversityChangsha 410083China School of Minerals Processing and Bioengineering Central South UniversityChangsha 410083China Department of Life Sciences Schrodinger BuildingUniversity of LimerickLimerick V94 T9PXIreland

腐殖化过程是赤泥土壤化及堆场生态修复的重要环节。本研究采用腐殖质分级和高通量测序技术,探究了秸秆和磷石膏联用对赤泥腐殖质组分和微生物群落的影响。结果表明,秸秆-磷石膏联用显著增加赤泥胡敏酸和富里酸含量,提高微生物群落多样... 详细信息

腐殖化过程是赤泥土壤化及堆场生态修复的重要环节。本研究采用腐殖质分级和高通量测序技术,探究了秸秆和磷石膏联用对赤泥腐殖质组分和微生物群落的影响。结果表明,秸秆-磷石膏联用显著增加赤泥胡敏酸和富里酸含量,提高微生物群落多样性和丰富度,促进赤泥腐殖化过程。施用秸秆后,赤泥中葡萄糖苷酶、纤维素水解酶、多酚氧化酶和过氧化物酶分别升高7.15~8.76倍、5.64~7.12倍、2.69~4.57倍和2.59~4.24倍,显著增加Devosiaceae、Rhizobiaceae、Flavobacteriaceae、Caulobacteraceae和Cellvibrionaceae等具有纤维素降解和固氮功能微生物类群相对丰度,提高微生物群落稳定性。研究结果为外源生物质促进腐殖质累积、驱动赤泥成土进程提供科学依据。

关键词：赤泥秸秆腐殖质组分微生物群落赤泥土壤化

Spontaneous Tumor Lysis Syndrome Secondary to Iatrogenic Acute Kidney Injury: A Case Report

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Case Reports in Clinical Medicine 2024年第5期13卷 155-161页

作者： Joseph Capito Mitchell Hoyson Amie M. Ashcraft Hassan Suleiman courtney S. Pilkerton Department of Family Medicine West Virginia University Morgantown WV USA Department of Clinical Family Medicine University of Rochester Medical Center Rochester NY USA Departments of Critical Care Medicine & Nephrology Mount Sinai New York City NY USA

Spontaneous Tumor Lysis Syndrome (STLS) is a rare oncologic condition caused by the breakdown of neoplastic tissue in the absence of traditional anti-tumor therapy. It is postulated that cancers with rapidly dividing cells lead to increased cell turnover which exceeds the kidneys’ ability to adequately filtrate by-products of cellular breakdown (i.e., phosphate, potassium, anduric acid), leading to end organ damage. It has been reported in the past that kidney failure is a sequelae of Tumor Lysis Syndrome (TLS), but there have been no reports that demonstrate acute kidney injury (AKI) preceding TLS. The case presented here demonstrates TLS in a patient with no formal cancer diagnosis, who had received no chemotherapy or radiation that was precipitated by an iatrogenic AKI with chlorthalidone and ibuprofen. This unusual pattern of AKI preceding STLS may provide insight into the pathophysiology of the condition and could possibly lead to greater understanding of this phenomenon.

关键词： Spontaneous Tumor Lysis Acute Kidney Injury Lymphoma Chlorthalidone NSAID

Histone Deacetylase Genes in Arabidopsis Development

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Journal of Integrative Plant Biology 2008年第7期50卷 875-885页

作者： courtney Hollende Department of Cell Biology and Molecular Genetics University of Maryland College ParkMaryland 20742USA

Histone acetylation and deacetylation are directly connected with transcriptional activation and silencing in eukaryotes. Gene families for enzymes that accomplish these histone modifications show surprising complexity in domain organization, tissue-specific expression, and function. This review is focused on the family of histone deacetylases （HDACs） that remove the acetyl group from core histone tails, resulting in a ＂closed＂ chromatin and transcriptional repression. In Arabidopsis, 18 HDAC genes are divided into three different types - RPD3-1ike, HD-tuin and sirtuin - with two or more members in each type. The structural feature of each HDAC class, the expression profile of each HDAC gene during development and functional insights of important family members are summarized here. It is clear that HDACs are an important class of global transcriptional regulators that play crucial roles in plant development, defense, and adaptation.

关键词： chromatin epigenetic regulation gene silencing histone deacetylase plant development

Role of MGST1 in reactive intermediate-induced injury

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World Journal of Gastroenterology 2011年第20期17卷 2552-2557页

作者： courtney S Schaffert Department of Biochemistry and Molecular Biology University of Nebraska Medical Center

Microsomal glutathione transferase (MGST1, EC 2.***.1.18) is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic electrophile intermediates and lipophilic hydroperoxides through its glutathione dependent transferase and peroxidase activities. It is expressed in high amounts in the liver, located both in the endoplasmic reticulum and the inner and outer mitochondrial membranes. This enzyme is activated by oxidative stress. Binding of GSH and modification of cysteine 49 (the oxidative stress sensor) has been shown to increase activation and induce conformational changes in the enzyme. These changes have either been shown to enhance the protective effect ascribed to this enzyme or have been shown to contribute to cell death through mitochondrial permeability transition pore formation. The purpose of this review is to elucidate how one enzyme found in two places in the cell subjected to the same conditions of oxidative stress could both help protect against and contribute to reactive oxygen species-induced liver injury.

关键词： Microsomal glutathione transferase 1 Oxidative stress Mitochondrial permeability transition Glutathione Liver injury

The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A2A receptor activation

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Cellular & Molecular Immunology 2015年第1期12卷 107-112页

作者： courtney M Lappas Department of Biology Lebanon Valley College Annville PA USA

Cytokinins are plant hormones that play an integral role in multiple aspects of plant growth and development. The biological functions of cytokinins in mammalian systems are, however, largely uncharacterized. The naturally occurring cytokinin zeatin riboside has recently been demonstrated to activate the mammalian adenosine A2A receptor, which is broadly expressed by various cell types including immune system cells, with the activation of the A2AR playing a role in the regulation of cells involved in both innate and adaptive immunity. We show for the first time that zeatin riboside modulates mammalian immune system activity via an A2AR-dependent mechanism. Specifically, zeatin riboside treatment induces the production of cyclic adenosine monophosphate （cAMP） by T lymphocytes and inhibits the production by CD3^＋CD4^＋ T cells of interferon （IFN）-γ, IL-2, tumor-necrosis factor （TNF）-α, IL-4 and IL-13, and the production by CD3^＋CD8^＋ T cells of IFN-γ, IL-2 and TNF-α. Additionally, the upregulation of CD25, CD69 and CD40L by activated T lymphocytes is modulated by zeatin riboside. Zeatin riboside treatment also potently inhibits thioglycollate-induced peritoneal leukocytosis. The immunomodulatory activities of zeatin riboside are blocked by co-treatment with the selective A2AR antagonist ZM241385. These data suggest that zeatin riboside possesses therapeutic potential as a mammalian immunomodulatory agent.

关键词： adenosine A2A receptors T lymphocytes zeatin riboside

Hydrocephalus Secondary to Intraventricular Myxopapillary Ependymoma: Case Report

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World Journal of Neuroscience 2024年第3期14卷 85-91页

作者： Juan Carlos Ayala-Alvarez Onyekachi Emmanuel Anyagwa Fátima Gabriela Macías-Ortiz Oluwatoyin Adalia Dairo courtney Storm Truebody Reza Badrnejad Aishwarya Bhuta Shashwat Sandeep Phade Srushti Kishor Jamdar Mostafa Yassin Vismaja Vijayan Neurology Department Hospital Civil Fray Antonio Alcalde Guadalajara Jalisco Mxico School of Medicine New Vision University Tbilisi Georgia

Ependymomas are a somewhat diverse category of glial tumors that often develop from the lining of the brain’s ventricles, or the spinal cord’s central canal. They make up 5% of all neuroepithelial tumors, 10% of paediatric brain tumors, and up to 33% of brain tumors in children under the age of three. Hydrocephalus is one of the complications, and it can be identified as progressive macrocephaly or increasing head circumference crossing percentiles, nausea, vomiting, poor appetite, irritability, and regression of developmental milestones.

关键词： Hydrocephalus Myxopapillary Ependymoma (MPE) Paediatrics Neurosurgery Glioma Intracranial Hypertension

Mainstreaming Early Warning Systems in Development and Planning Processes: Multilevel Implementation of Sendai Framework in Indus and Sahel

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International Journal of Disaster Risk Science 2015年第2期6卷 189-199页

作者： Asim Zia courtney Hammond Wagner Department of Community Development and Applied Economics University of Vermont Department of Computer Science University of Vermont Rubenstein School of the Environment and Natural Resources University of Vermont

The third UN World Congress on Disaster Risk Reduction, held in Sendai, Japan in March 2015, agreed on a new framework to guide disaster risk reduction policy and practice for the next 15 years. The Sendai Framework for Disaster Risk Reduction 2015–2030(SFDRR) leaves important implementation issues unspecified and potentially creates both problems and opportunities for complex,multilevel governance systems in coping with hazards and disastrous events. Early warning systems(EWS), if built into the mainstream of planning for development and disaster relief and recovery, could present a significant opportunity to realize many SFDRR goals. We explore the complexities of using hydrometeorological EWS to prepare for drought and flood disasters in the densely populated communities of Pakistan’s Indus River Basin in contrast to the African Sahel’s less densely settled grasslands. Multilevel governance systems are often dominated by a topdown, technocentric, centralized management bias and have great difficulty responding to the needs of peripheral and vulnerable populations. People-centered, bottom-up approaches that incorporate disaggregated communities with local knowledge into a balanced, multilevel disaster risk management and governance structure have adramatically better chance of realizing the SFDRR goals for disaster risk reduction.

关键词： Early warning systems Infrastructure development Land-use planning Policy implementation Risk governance Sendai Framework Science-policy interface