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Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

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Neural Regeneration Research 2018年第10期13卷 1719-1730页

作者： paul denver paula L.McClean Greater Los Angeles Veterans Affairs Healthcare System West Los Angeles Medical Center and Department of NeurologyUniversity of CaliforniaLos AngelesCAUSA Centre for Molecular Biosciences University of UlsterColeraine Northern Ireland UK Northern Ireland Centre for Stratified Medicine ClinicalTranslational and Research Innovation Centre (C-TRIC)University of UlsterDerry/Londonderry Northern Ireland UK

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

关键词： Alzheimer's disease aging inflammation cognitive function spatial learning insulin signaling synapses cytokines

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Psychosocial factors and their association with reflux oesophagitis,Barrett's oesophagus and oesophageal adenocarcinoma

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World Journal of Gastroenterology 2013年第11期19卷 1770-1777页

作者： paul denver Michael Donnelly Liam J Murray Lesley A Anderson Centre for Public Health Queen's University BelfastBelfast BT12 6BJNorthern IrelandUnited Kingdom

AIM:To investigate the role of psychological characteristics as risk factors for oesophageal adenocarcinoma(OAC),as well as the reflux-mediated precursor ***:An all-Ireland population-based case-control study recruited 230 reflux oesophagitis(RO),224 Barrett's oesophagus(BO) and 227 OAC patients and 260 *** case/control group completed measures of stress,depression,self-efficacy,self-esteem,repression and social support.A comparative analysis was undertaken using polytomous logistic regression adjusted for potential ***:Compared to controls,OAC patients were almost half as likely to report high stress levels over their lifetime(P = 0.010,OR 0.51;95%CI:0.29-0.90)and 36% less likely to report having experienced depression(OR 0.64;95%CI:0.42-0.98).RO patients reported significantly higher stress than controls particularly during middle-and senior-years(P for trends < 0.001).RO patients were 37% less likely to report having been highly emotionally repressed(OR 0.63;95%CI:0.41-0.95).All case groups(OAC,RO and BO) were more likely than controls to report having had substantial amounts of social support(OR 2.84;95%CI:1.63-4.97;OR 1.97;95%CI:1.13-3.44 and OR 1.83;95%CI:1.03-3.24,respectively).CONCLUSION:The improved psychological profile of OAC patients may be explained by response *** role of psychological factors in the development of OAC requires further investigation.

关键词： Reflux oesophagitis Barrett’s oesophagus Oesophageal adenocarcinoma Adjustment Psychological Psychosocial factors

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Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep

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Journal of Animal Science and Biotechnology 2015年第2期6卷 222-229页

作者： Laura D Brown Stephanie R Thorn Alex Cheung Jinny R Lavezzi Frederick C Battaglia paul J Rozance Perinatal Research Center Division of Neonatology Department of Pediatrics University of Colorado Denver School of Medicine Center for Women’s Health Research University of Colorado Denver School of Medicine

Background： The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short （2-wk） and long （8-wk） durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions （1-wk hyperinsulinemic-isoglycemic clamp） to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. Results： A maternal insulin infusion resulted in lower maternal （50%, P 〈 0.01） and fetal （35-45%, P 〈 0.01） mannose concentrations, which were highly correlated （r^2 = 0.69, P 〈 0.01）. A fetal insulin infusion resulted in a 50% reduction of fetal mannose （P 〈 0.05）. Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions. Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose （P 〈 0.01）. Conclusions： Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted.

关键词： Fructose Glucose Inositol Insulin Mannose Pregnancy

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RECENT ADVANCES IN THE TREATMENT OF ADVANCED NON-SMALL CELL LUNG CANCER

RECENT ADVANCES IN THE TREATMENT OF ADVANCED NON-SMALL CELL ...

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中国抗癌协会第六届临床肿瘤协作中心（CSCO）学术年会

作者： paul A. Bunn Jr. MD University of Colorado Cancer Center Denver CO.

＜正＞Lung cancer is the leading cause of cancer death throughout the world. In the U. S., where lung cancer accounts for 28% of all cancer deaths, there are more new cases of breast and prostate cancer but there are more deaths from lung cancer than from breast, prostate and colorectal can cers combined. The 5-year survival rate in the U. S. is 14%, which is very poor but better than the 5% 5-year survival rate that was reported in the 1960s. The majority of patients （75%） pre-

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Recent Advanced in the Treatment of Advanced Non-Small Cell Lung Cancer

Recent Advanced in the Treatment of Advanced Non-Small Cell ...

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中国抗癌协会临床肿瘤学协作中心（CSCO）第五届年会

作者： paul A. Bunn Jr. MD University of Colorado Cancer Center Denver CO.

＜正＞Lung cancer is the leading cause of cancer death throughout the world. In the U. S., where lung cancer accounts for 28％ of all cancer deaths, there are more new cases of breast and prostate cancer but there are more deaths from lung cancer than from breast, prostate and colorectal cancers com bined. The 5-year survival rate in the U.S. is 14％, which is very poor but better than the 5％ 5-year survival rate that was reported in the 1960s. The majority of patients (75％ present with stage Ⅲ or

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Pulsed Laser Annealed Ga Hyperdoped Poly-Si/SiO_(x)Passivating Contacts for High-Efficiency Monocrystalline Si Solar Cells

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Energy & Environmental Materials 2023年第3期6卷 388-399页

作者： Kejun Chen Enrico Napolitani Matteo De Tullio Chun-Sheng Jiang Harvey Guthrey Francesco Sgarbossa San Theingi William Nemeth Matthew Page paul Stradins Sumit Agarwal David L.Young Colorado School of Mines 1500 Illinois StGolden Colorado 80401USA Dipartimento di Fisica e Astronomia and CNR-IMM Universit`a degli Studi di Padovavia Marzolo 8PadovaItaly National Renewable Energy Laboratory 15013 Denver West ParkwayGolden Colorado 80401USA

Polycrystalline Si(poly-Si)-based passivating contacts are promising candidates for high-efficiency crystalline Si solar *** show that nanosecond-scale pulsed laser melting(PLM)is an industrially viable technique to fabricate such contacts with precisely controlled dopant concentration profiles that exceed the solid solubility *** demonstrate that conventionally doped,hole-selective poly-Si/SiO_(x)contacts that provide poor surface passivation of c-Si can be replaced with Ga-or B-doped contacts based on non-equilibrium *** overcome the solid solubility limit for both dopants in poly-Si by rapid cooling and recrystallization over a timescale of∼25 *** show an active Ga dopant concentration of∼3×10^(20)cm^(−3)in poly-Si which is six times higher than its solubility limit in c-Si,and a B dopant concentration as high as∼10^(21) cm^(−3).We measure an implied open-circuit voltage of 735 mV for Ga-doped poly-Si/SiO_(x)contacts on Czochralski Si with a low contact resistivity of 35.5±2.4 mΩcm^(2).Scanning spreading resistance microscopy and Kelvin probe force microscopy show large diffusion and drift current in the p-n junction that contributes to the low contact *** results suggest that PLM can be extended for hyperdoping of other semiconductors with low solubility atoms to enable high-efficiency devices.

关键词： Ga hyperdoping Ga passivating contacts poly-Si/SiO_(x) pulsed laser melting silicon solar cell

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Efficacy and safety of peroral endoscopic myotomy after prior sleeve gastrectomy and gastric bypass surgery

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World Journal of Gastrointestinal Endoscopy 2020年第12期12卷 532-541页

作者： Jennifer M Kolb Daniel Jonas Mateus Pereira Funari Hazem Hammad paul Menard-Katcher Mihir S Wagh Division of Gastroenterology University of Colorado-DenverAuroraCO 80045United States Department of Internal Medicine University of Colorado HospitalAuroraCO 80045United States Gastrointestinal Endoscopy Unit Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao PauloSao paulo 05403000Sao pauloBrazil Interventional Endoscopy Division of GastroenterologyUniversity of Colorado-DenverAuroraCO 80045United States

BACKGROUND Per-oral endoscopic myotomy(POEM)is safe and effective for the treatment of *** is limited data on performance of POEM in patients with altered upper gastrointestinal anatomy,especially after bariatric *** in patients with prior sleeve gastrectomy have not been *** To assess the efficacy and safety of POEM in patients with prior bariatric *** A prospective POEM database was reviewed from 3/2017-5/2020 to identify patients who underwent POEM after prior bariatric *** was assessed by technical success(defined as the ability to successfully complete the procedure)and clinical success[decrease in Eckardt score(ES)to≤3 post procedure].Safety was evaluated by recording adverse *** Six patients(50%male,mean age 48 years)with a history of prior bariatric surgery who underwent POEM were *** had prior sleeve gastrectomy(SG)and three prior Roux-en-Y gastric bypass(RYGB).Four patients had achalasia subtype II and 2 had type ***(4)patients had undergone previous achalasia *** success was 100%.Clinical success was achieved in 4(67%)patients at mean follow-up of 21 *** one of the clinical failures,EndoFLIP evaluation demonstrated adequate treatment and candida esophagitis was noted as the likely cause of *** were no major adverse *** POEM is technically feasible after both RYGB and SG and offers an effective treatment for this rare group of patients where surgical options for achalasia are limited.

关键词： Obesity Bariatric surgery Achalasia Peroral endoscopic myotomy Sleeve gastrectomy Gastric bypass

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EARLY VASCULAR GRAFTING TO PREVENT UPPER EXTREMITY NECROSIS AFTER ELECTRICAL BURNS INDICATIONS FOR SURGERY

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中华医学杂志(英文版) 1986年第8期99卷 679-684页

作者：王学威 BrianB.Roberts RomanL.Zapata-Sirvent William A.Robenson J.paul Waymark EdwardJ.Law BruceG.Mac Millan Departments of Medicine and Surgery University of Colorado Health Sciences Center Denver Colorado USA Departments of Burns Beijing Jishuitan Hospital and Beijing Institute of Traumatology and Orthopedics Beijing Shriners Burns Institute Cincinnati Ohio USA

In the treatment of electrically burned wrists exhibiting restricted blood circulation, the proper clinical assessment of certain early signs in the period of treatment is of great importance to the reasonable and effective performance of early vascular *** are analysis and summary of six unsuccessful cases and the possible indications for surgery.

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海岸湿地在飓风防护中的价值

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AMBIO－人类环境杂志 2008年第4期37卷 229-236页

作者： Robert Costanza Octavio Pérez-Maqueo M. Luisa Martinez paul Sutton Sharolyn J. Anderson Kenneth Mulder 唐晓宇（译）王书磊（校）张晓琴（校） Gund生态经济研究所 Instituto de Ecologla A．C． km 2．5 antigua carretera a Coatepecno351Congregaci ón El HayaXalapaVer．91070、México Department of Geography University of DenverDenverCO80208USA 格林高山大学不详

海岸湿地可以减少飓风对沿海群落的破坏作用。把1980年以来美国34次主要飓风在其袭击区所造成的单位国民生产总值损失的自然对数值作为因变量,风速和飓风袭击区湿地面积的自然对数值作为自变量,回归模型显示两者之间的差异极显著,说明... 详细信息

海岸湿地可以减少飓风对沿海群落的破坏作用。把1980年以来美国34次主要飓风在其袭击区所造成的单位国民生产总值损失的自然对数值作为因变量,风速和飓风袭击区湿地面积的自然对数值作为自变量,回归模型显示两者之间的差异极显著,说明了其相对损失的差别的60%。在上述模型中,每减少1 hm^2的湿地面积,来自特定风暴造成的风暴损害将平均增加33 000美元的损失(中值5000美元)。利用这个关系,把各年度不同强度飓风发生的概率考虑在内,我们以1km×1km为像素,以州为单元将湿地的年度价值绘制成图,湿地年度价值的变化范围为250～51 000美元/hm^2·a,平均价值为8240美元/hm^2·a(中值3230美元/hm^2·a),这显著高于以前估算的湿地价值。据估算,美国的海岸湿地目前能够提供的保护作用相当于232亿美元/a。在风暴防护中,海岸湿地是一种有价值的、能够自我维持的"水平堤防",并且能够提供垂直堤防所不能提供的许多其他的生态系统功能。对于人类社会来说,对沿海湿地的修复与维护是一种极其划算的战略性投资。

关键词：海岸湿地平均价值飓风防护国民生产总值生态系统功能湿地面积模型显示

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麻醉专科培训项目中丙泊酚滥用的调查研究

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麻醉与镇痛 2008年第5期4卷 89-94页

作者： paul E. Wischmeyer Bradley R. Johnson Joel E. Wilson Colleen Dingmann Heidi M. Bachman Evan Roller Zung Vu Tran Thomas K. Henthorn 谢鹏(译) 喻田(校) Department of Anesthesiology University of Colorado Denver Colorado Department of Chemistry Valparaiso University Valparaiso Indiana Department of Biostatistics University of Colorado Denver Colorado 不详

背景尽管传统观点并不认为丙泊酚是一种可以滥用的药物，但亚麻醉剂量的丙泊酚有潜在的滥用可能。我们通过本项调查研究来评估麻醉专科丙泊酚滥用的发生率及其转归。方法调查内容以电子邮件方式，发送到美国126个麻醉专科培训项目。结... 详细信息

背景尽管传统观点并不认为丙泊酚是一种可以滥用的药物，但亚麻醉剂量的丙泊酚有潜在的滥用可能。我们通过本项调查研究来评估麻醉专科丙泊酚滥用的发生率及其转归。方法调查内容以电子邮件方式，发送到美国126个麻醉专科培训项目。结果此项调查的回复率为100％。在过去的10年中，18％的科室报告存在一起或多起丙泊酚滥用或挪用。本研究显示，最近10年，麻醉实施者中丙泊酚滥用的发生率为10／10000，比前次调研的结果增加5倍（P=0．005）。在上报的25个滥用丙泊酚的个案中，有7人死于丙泊酚滥用（占28％），其中6人是住院医生。约有71％的科室没有对丙泊酚建立起类似阿片类药物管理的监督系统。在滥用发生期间，科室没有对丙泊酚进行监控（如药品清点），与滥用发生率之间存在一定的关联（P=0．048）。结论在过去10年中，麻醉专科培训项目中丙泊酚滥用的发生率似乎呈增长趋势，多数死亡病例发生在住院医师身上。许多科室没有对丙泊酚进行药品清点和监控。令人担忧的是，所有报道有丙泊酚滥用致死的科室都没有对丙泊酚进行药品清点。

关键词：亚麻醉剂量培训项目丙泊酚专科药物管理发生率电子邮件住院医生

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