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Amyloidβ-based therapy for Alzheimer’s disease:challenges,successes and future

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3374-3399页

作者： Yun Zhang Huaqiu Chen Ran Li keenan Sterling Weihong Song National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina The Second Affiliated Hospital and Yuying Children’s Hospital Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceWenzhou Medical UniversityWenzhouZhejiangChina Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouverBC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiangChina

Amyloidβprotein(Aβ)is the main component of neuritic plaques in Alzheimer’s disease(AD),and its accumulation has been considered as the molecular driver of Alzheimer’s pathogenesis and progression.Aβhas been the prime target for the development of AD ***,the repeated failures of Aβ-targeted clinical trials have cast considerable doubt on the amyloid cascade hypothesis and whether the development of Alzheimer’s drug has followed the correct course.

关键词： Alzheimer Aβ clinical

Microbial community coalescence and nitrogen cycling in simulated mortality decomposition hotspots

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Ecological Processes 2023年第1期12卷 608-624页

作者： Sarah W.keenan Alexandra L.Emmons jennifer M.DeBruyn Department of Geology and Geological Engineering South Dakota School of Mines and Technology501 East St.Joseph StreetRapidSD 57701USA Department of Anthropology University of TennesseeKnoxvilleTNUSA Department of Biosystems Engineering and Soil Science University of Tennessee2506 E.J.Chapman DriveKnoxvilleTN 37996USA

Background The pulsed introduction of dead plant and animal material into soils represents one of the primary mechanisms for returning organic carbon(C)and nitrogen(N)compounds to biogeochemical *** of animal carcasses provides a high C and N resource that stimulates indigenous environmental microbial communities and introduces non-indigenous,carcass-derived microbes to the ***,the dynamics of the coalesced microbial communities,and the relative contributions of environment-and carcass-derived microbes to C and N cycling are *** test whether environment-derived,carcass-derived,or the combined microbial communities exhibited a greater influence on C and N cycling,we conducted controlled laboratory experiments that combined carcass decomposition fluids and soils to simulate carcass decomposition *** selectively sterilized the decomposition fluid and/or soil to remove microbial communities and create different combinations of environment-and carcass-derived communities and incubated the treatments under three temperatures(10,20,and 30℃).Results Carcass-derived bacteria persisted in soils in our simulated decomposition scenarios,albeit at low *** communities had higher respiration rates at 10 and 30℃ compared to soil or carcass communities ***,at higher temperatures,mixed communities had reduced diversity,but higher respiration,suggesting functional *** communities treatments also provided evidence that carcass-associated microbes may be contributing to ammonification and denitrification,but that nitrification is still primarily carried out by native soil *** Our work yields insight into the dynamics of microbial communities that are coalescing during carcass decomposition,and how they contribute to recycling carcasses in terrestrial ecosystems.

关键词： Carcass decomposition Microcosm Nitrogen Carbon Biogeochemical cycling Coalescence

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Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease:A paradigm shift from acid to bacteria?

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World journal of Gastroenterology 2021年第18期27卷 2054-2072页

作者： Steve M D'Souza Kevin Houston Lauren keenan Byung Soo Yoo Parth j Parekh David A johnson Department of Internal Medicine Division of GastroenterologyEastern Virginia Medical SchoolNorfolkVA 23502United States

Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and *** interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases,including those impacting the *** relatively stable,there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome(EM)and the *** changes are thought to be a product of age,diet,antibiotic and other medication use,oral hygiene,smoking,and/or expression of antibiotic products(bacteriocins)by other *** effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation,systemic inflammation,and ultimately disease *** has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is,therefore,not merely the result of esophageal mucosal exposure to corrosives(i.e.,acid).Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory ***,we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief(i.e.,acid suppression).

关键词： Microbiome Gastroesophageal reflux disease Probiotics Prebiotics Bacteriocins Dysbiosis Barrett’s esophagus Esophageal cancer Esophagitis Eosinophilic esophagitis

Perceptions of the effectiveness of Advanced Practice Nurses on a neurosurgery unit in a Canadian Tertiary Care Centre:A pre-and-post implementation design

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International journal of Nursing Sciences 2018年第2期5卷 138-143页

作者： Alanna M.keenan Erin E.Mutterback Kristi M.Velthuizen Monika E.Pantalone Kira L.Gossack-keenan The Ottawa Hospital OttawaOntarioCanada University of Ottawa OttawaOntarioCanada McMaster University HamiltonOntarioCanada

Objectives:A framework for the advanced practice nurse(APN)role was developed in our Canadian Tertiary Care Centre,delineating five domains of advanced nursing practice:clinical practice,consultation,research,education and *** goal of this study was to evaluate perceptions of the effectiveness of the implementation of an innovative APN role on an in-patient Neurosurgery ***:A pre-and-post implementation design,incorporating both qualitative and quantitative data,was *** innovative APN role was implemented within the Neurosurgery program focusing on the clinical domain and required the successful candidates to be NP *** APN role was designed to improve patient flow,documentation,communication and patient and staff *** primary outcomes were measured:pre-implementation questionnaire(nurses),post-implementation questionnaire(nurses and residents)and number of pages to the on-call ***:Survey scores by nurses and residents indicated improvement across all aspects *** scores increased from 1.1 to 2.6,reflecting an overall statistically significant *** number of pages to the on-call resident also showed a ***:Perceptions of patient care delivery and professional collaboration improved following implementation of the APN *** indicated that APNs significantly impacted patient care and improved nurses and residents'job satisfaction.

关键词： Advanced practice nursing Delivery of health care Patient care team Pre-post tests Professional practice gaps

Clinical classification of symptomatic heterotopic pancreas of the stomach and duodenum:A case series and systematic literature review

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World journal of Gastroenterology 2022年第14期28卷 1455-1478页

作者： Michael T Le Compte Brandon Mason keenan j Robbins Motoyo Yano Deyali Chatterjee Ryan C Fields Steven M Strasberg William G Hawkins Department of Surgical Oncology University of North CarolinaRaleighNC 27608United States Department of Radiology Stillwater Medical CenterStillwaterOK 74074United States Department of General Surgery Washington University St.LouisSt.LouisMO 63110-8109United States Department of Radiology Mayo ClinicPhoenixAZ 8505United States Department of Pathology and Immunology MD Anderson Cancer CenterHoustonTX 77030United States Department of Surgical Oncology Washington University School of MedicineSt.LouisMO 63110-8109United States Section of Hepatobiliary-Pancreatic and GI Surgery Washington University St.LouisSt.LouisMO 63110United States

BACKGROUND Heterotopic pancreas(HP)is an aberrant anatomic malformation that occurs most commonly in the upper gastrointestinal *** the majority of heterotopic pancreatic lesions are asymptomatic,many manifest severe clinical symptoms which require surgical or endoscopic *** of the clinical manifestations and symptoms of HP is limited due to the lack of large volume studies in the *** purpose of this study is to review symptomatic cases at a single center and compare these to a systematic review of the literature in order to characterize common clinical manifestations and treatment of this *** To classify the common clinical manifestations of heterotopic *** A retrospective review was conducted of pathologic samples containing heterotopic pancreas from *** was limited to HP of the upper gastrointestinal tract due to the frequency of presentation in this *** patients were identified from review of the medical records and clinical symptoms were *** were compared to a systematic review of the literature utilizing Pub Med and Embase searches for papers pertaining to heterotopic *** describing symptomatic presentation of HP were selected for *** including demographics,symptoms,presentation and treatment were compiled and *** Twenty-nine patient were identified with HP at a single center,with six of these identified has having clinical *** manifestations included,gastrointestinal bleeding,gastric ulceration with/without perforation,pancreatitis,and gastric outlet *** review of the literature yielded 232 publications detailing symptomatic cases with only 20 studies describing ten or more *** and multi-patient studies were combined to form a cohort of 934 symptomatic *** majority of patients presented with abdominal pain(67%)combined with one of the following clinical catego

关键词： Heterotopic pancreas Ectopic pancreas Aberrant pancreas Pancreatic rest Groove pancreatitis

Alleviative effects of Cannabis flower on migraine and headache

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journal of Integrative Medicine 2020年第5期18卷 416-424页

作者： Sarah SStith jegason PDiviant Franco Brockelman keenan Keeling Branden Hall Storri Lucern jacob M.Vigil Deparment of Economics Faculy of Economics.University of New MexicoAlbuiquerqueNew Mexico 87131USA Department of Psychology Sudent of Psychologv.University of New Mexico.AlbuquerqueNew Mexico 87131.USA Morebetter Ltd.Sofwure Developer HatsvileMaryland 20781USA Department of Psycholog Faculy of Psychology.University of New MexicoAlbuquerqueNew Mexico 87131USA

Objective: Few studies to date have measured the real-time effects of consumption of common and commercially available Cannabis products for the treatment of headache and migraine under naturalistic conditions. This study examines, for the first time, the effectiveness of using dried Cannabis flower, the most widely used type of Cannabis product in the United States, in actual time for treatment of headache-and migraine-related pain and the associations between different product characteristics and changes in symptom intensity following Cannabis ***: Between 06/10/2016 and 02/12/2019, 699 people used the Releaf Application to record realtime details of their Cannabis use, including product characteristics and symptom intensity levels prior to and following self-administration;data included 1910 session-level attempts to treat headache-(1328 sessions) or migraine-related pain(582 sessions). Changes in headache-or migraine-related pain intensity were measured on a 0–10 scale prior to, and immediately, following Cannabis ***: Ninety-four percent of users experienced symptom relief within a two-hour observation window. The average symptom intensity reduction was 3.3 points on a 0–10 scale(standard deviation = 2.28,Cohen's d = 1.58), with males experiencing greater relief than females(P < 0.001) and a trend that younger users(< 35 years) experience greater relief than older users(P = 0.08). Mixed effects regression models showed that, among the known(i.e., labeled) product characteristics, tetrahydrocannabinol levels 10% and higher are the strongest independent predictors of symptom relief, and this effect is particularly prominent in headache rather than migraine sufferers(P < 0.05), females(P < 0.05) and younger users(P < 0.001). Females and younger users also appear to gain greater symptom relief from flower labeled as ‘‘C. indica" rather than ‘‘C. sativa" or other hybrid ***: These results suggest that whole dried Cannabis flowe

关键词： Migraine Headache Cannabis Marijuana Symptom management

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Mining Rehabilitation in New South Wales （Australia） and Germany

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journal of Earth Science and Engineering 2015年第8期5卷 499-511页

作者： Lisa j. K. Zillig Naomi keenan Tim Roberts University of Duisburg-Essen Essen 45141 Germany Tom Farrell Institute for the Environment the University of Newcastle Callaghan NSW 2308 Australia

The rehabilitation of coal mines is an up-to-date issue, heavily discussed not only by the industry but also by scientists and the adjacent communities since open cut coal mining has extensive impacts affecting all parties. Whereas, before and during the mining process not only nature but sometimes also the population of a whole region has to give way to a mine, the consequences of the operations remain long after mining closure. Typically a once intact and functioning ecosystem is replaced with a destroyed wideness evocative of a moon landscape. Fortunately, the awareness of the need to rehabilitate the destroyed nature is increasing steadily and all involved parties are making efforts to improve the situation, even if it is a major challenge to bring all parties to a consensus. Therefore, a legislative basis is required and the know-how of optimal rehabilitation solutions must be developed. In this article the rehabilitation of mined land in Australia and Germany are compared. More precisely the article will present an overview of the legislative regulations, certain applied methods of rehabilitation work and the problems that are likely to occur in respect to the influence of mining on nature.

关键词： Mining rehabilitation mining Australia mining Germany mine closure legislation mining rehabilitation.

Reduced striatal volumes in Parkinson’s disease:a magnetic resonance imaging study

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Translational Neurodegeneration 2012年第1期1卷 132-139页

作者： Toni L Pitcher Tracy R Melzer Michael R MacAskill Charlotte F Graham Leslie Livingston Ross j.keenan Richard Watts john C Dalrymple-Alford Tim j Anderson Department of Medicine University of OtagoChristchurchNew Zealand New Zealand Brain Research Institute 66 Stewart StChristchurch 8011New Zealand Department of Psychology University of CanterburyChristchurchNew Zealand College of Medicine University of VermontBurlingtonVTUSA Christchurch Radiology Group ChristchurchNew Zealand Department of Neurology Canterbury District Health BoardChristchurchNew Zealand

Background:The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease(PD)is still poorly ***:High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were ***,caudate,and intracranial volumes were manually traced in the axial plane of 3D reconstructed *** nuclei volumes were normalized to intracranial volume for statistical *** status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr *** status was assessed using global status tests and detailed neuropsychological ***:Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and *** volumes were reduced by 11%(p=0.001)and putamen volumes by 8.1%(p=0.025).PD striatal volumes were not found to be significantly correlated with cognitive or motor ***:Small,but significant reductions in the volume of both the caudate and putamen occur in PD *** reductions are independent of the effects of age and gender,however the relation of these reductions to the functional loss of dopamine,which is characteristic of PD,remains unclear.

关键词： Magnetic resonance imaging Volumetry Caudate Putamen Parkinson’s disease

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定量CT测量动物肝脏脂肪含量的实验研究

放射学实践 2017年第5期32卷 466-470页

作者：徐黎端木羊羊张勇 keenan brown 张曼玲程晓光北京积水潭医院放射科北京100035 Mindways Software AustinTXUSA 国家食品质量安全监督检验中心化学分析室北京100094

目的:以Soxhlet化学萃取法的测量结果为参考标准,探讨定量CT(QCT)对离体动物肝脏标本脂肪含量测量的准确性。方法:选取5块猪肝、5块鹅肝和10块鸭肝,分别使用QCT和Soxhlet化学萃取法测量每个样本的脂肪含量。对QCT测得的肝脏脂肪含量(Fat... 详细信息

目的:以Soxhlet化学萃取法的测量结果为参考标准,探讨定量CT(QCT)对离体动物肝脏标本脂肪含量测量的准确性。方法:选取5块猪肝、5块鹅肝和10块鸭肝,分别使用QCT和Soxhlet化学萃取法测量每个样本的脂肪含量。对QCT测得的肝脏脂肪含量(Fat%Q)和Soxhlet化学萃取法测得的肝脏脂肪含量(Fat%S)进行比较,并使用线性回归分析研究Fat%Q与Fat%S之间的关系。结果:Soxhlet化学萃取法测得的猪肝、鸭肝和鹅肝的脂肪含量分别为0.5%~2.3%、7.2%~21.0%和35.0%~52.6%,QCT测得的肝脏脂肪含量低于Soxhlet化学萃取法,但两种方法的测量结果差异无统计学意义(P=0.052)。两种方法的测量结果高度相关(r=0.962,P<0.001),Fat%S可以通过线性方程Fat%S=0.74,Fat%Q+7.272(r2=0.965,P<0.001)进行预测。结论:以化学Soxhlet萃取法作为验证参考标准,使用常规CT和QCT体模能够准确测量离体动物肝脏样本的脂肪含量。

关键词：肝脏脂肪含量定量CT 体层摄影术,X线计算机 Soxhlet化学萃取法

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