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Long-term cost and efficacy analysis of latanoprost versus timolol in glaucoma patients in Germany

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 155-159页

作者： Ulrich Thelen Dietmar Schnober Sonja Schlzel Michael S.Kristoffersen Lindsay A.Nelson Jeanette A.stewart william c.stewart Westfalische Wilhelms-Universitat AugenarztpraxisMünster Germany Augenarzt Werdohl Germany Department of Surgery Institutes of Molecular Medicine University of Freiburg PRN Pharmaceutical Research Network LLC Cheyenne WY USA

AIM: To evaluate 5-year effectiveness and cos between latanoprost or timolol monotherapy in a pilot ***: A retrospective, multi-center trial performed at 6 sites in Germany of patients who had a diagnosis of primary open-angle or pigmentary glaucoma, in at least one eye, initiated on monotherapy with latanoprost or timolol maleate. Qualified consecutive charts were reviewed in which 5-year efficacy, safety and cost data was ***: Seventy-seven latanoprost and 49 timolo patients were included, at the final visit no difference existed between the two groups in disc parameters including: rim area, rim area/disc area ratio, cup volume or vertical cup/disc ratio (P >0.05). There was no difference in intraocular pressure (IOP) between the initial latanoprost (17.4 ±2.6) and timolol (16.3 ±2.8mmHg) groups. There was less change in medicines over the follow-up period (0.1 vs 0.8) and fewer medications at the final visit (1.2 vs 1.8) with latanoprost compared to timolol. No patient treated with latanoprost discontinued therapy during follow-up, while 12% discontinued timolol mostly due to inadequate IOP control. cost/year was less with initial timolol ($458±236) as compared to latanoprost ($552±202). cONcLUSION: Patients begun on latanoprost o timolol and followed over 5 years may have similar clinical outcomes. However, timolol patients may require more medicines and medicine changes to control IOP for long-term, but at a lower cost.

关键词： glaucoma economic efficacy safety latanoprost timolol Germany

拉坦、曲伏及比马前列素治疗青光眼的成本效用分析(英文)

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国际眼科杂志 2009年第5期9卷 812-816页

作者： william c.stewart Jeanette A stewart Marko A Mychaskiw PRN制药研究公司美国德克萨斯州达拉斯辉瑞公司美国纽约州纽约市

目的:评估拉坦前列素,曲伏前列素和比马前列素在挪威,瑞典及丹麦(斯堪的纳维亚)治疗开角型青光眼的成本效用。方法:建立马尔可夫卫生经济学决策分析模型,评估比较前列腺素类似物的成本效用。健康状态为稳定及进展期青光眼。原发性开角... 详细信息

目的:评估拉坦前列素,曲伏前列素和比马前列素在挪威,瑞典及丹麦(斯堪的纳维亚)治疗开角型青光眼的成本效用。方法:建立马尔可夫卫生经济学决策分析模型,评估比较前列腺素类似物的成本效用。健康状态为稳定及进展期青光眼。原发性开角型青光眼和表皮剥脱性青光眼的转换概率均由发表的医学文献数据计算所得。通过对分散遍及于各国家的45位眼科医生进行调查获得临床医疗模式。各国家的具体单位成本包括药费,就诊费,诊断及治疗费。生命质量权重值指定为视力0.50 ～0.84,时间范围为5a。所有分析均为付款人观点成本效益分析,成本结果每年降低3%。结果:在挪威和瑞典,拉坦前列素较曲伏前列素和比马前列素费用低而效益高,拉坦前列素比其他药物费用低达4%。在丹麦,所有三种药物的费用在彼此的1.5%之内,比马前列素与曲伏前列素费用相当,而较拉坦前列素费用略低,但是拉坦前列素较曲伏前列素和比马前列素效益高。各国家所有药物的效用在一个窄范围内。结论:在斯堪的纳维亚,拉坦前列素为其他可买到的前列腺素类似物提供了经济有效的替代物。

关键词：成本拉坦前列素曲伏前列素比马前列素马尔可夫模型

Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases

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Neural Regeneration Research 2022年第4期17卷 867-874页

作者： Huifangjie Li william c.Knight Jinbin Xu Department of Radiology Washington University School of MedicineSt.LouisMOUSA

Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain *** mechanisms responsible for the disease progression in neurodegeneration are not fully *** this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced *** performed Spearman and Mantel-cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and *** progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory *** progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals *** with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in *** age of onset also affected disease *** requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research center(ADRc)Biospecimens committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved

关键词： Alzheimer disease disease progression Lewy body diseases microglia neurodegeneration oxidative damage striatum survival

conversion of soy molasses,soy solubles,and dried soybean carbohydrates into ethanol

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International Journal of Agricultural and Biological Engineering 2013年第1期6卷 62-68页

作者： craig c.Long william R.Gibbons Biology and Microbiology Department South Dakota State UniversityBrookingsSD57007 USA

Soy molasses and soy solubles are byproducts of the conventional soy protein concentrate and soy protein isolate manufacturing processes,*** of the carbohydrates in these byproducts into ethanol was *** amounts of commercial cellulase enzymes(Novozyme cellulase,β-glucosidase,and pectinase)were added to soy molasses and soy solubles solutions prepared at various solid loading rates(33%,50%,60%,75%,and 80%)to hydrolyze oligosaccharides,followed by fermentation for 96 h using Saccharomyces cerevisiae NRRL Y-2034 and Scheffersomyces stipitis NRRL ***-extracted soybean meal(SBM)carbohydrates were also fermented for 96 h without *** and *** produced about 12.5-45.0 g/L and 6.0-28.0 g/L ethanol,respectively,on molasses and solubles across these solid loading *** *** produced about 6.5-17 g/L ethanol and *** produced about 6.5-22 g/L ethanol on ethanol-extracted carbohydrates.

关键词： ethanol production soy molasses soy solubles oligosaccharides

An Arabidopsis Lipid Flippase Is Required for Timely Recruitment of Defenses to the Host- Pathogen Interface at the Plant cell Surface

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Molecular Plant 2017年第6期10卷 805-820页

作者： william Underwood Andrew Ryan Shauna c. Somerville Energy Biosciences Institute Department of Plant and Microbial Biology University of california Berkeley CA 94720 USA USDA-ARS Red River Valley Agricultural Research center Sunflower and Plant Biology Research Unit Fargo ND 58102-2765 USA Division of Biological Sciences University of California San Diego CA 92161 USA

Deposition of cell wall-reinforcing papillae is an integral component of the plant immune response. TheArabidopsis PENETRATION 3 （PEN3） ATP binding cassette （ABc） transporter plays a role in defense against numerous pathogens and is recruited to sites of pathogen detection where it accumulates within papillae. However, the trafficking pathways and regulatory mechanisms contributing to recruitment of PEN3 and other defenses to the host-pathogen interface are poorly understood. Here, we report a confocal microscopy-based screen to identify mutants with altered localization of PEN3-GFP after inoculation with powdery mildew fungi. We identified a mutant, aberrant localization of PEN3 3 （alp3）, displaying accumulation of the normally plasma membrane （PM）-Iocalized PEN3-GFP in endomembrane compartments. The mutant was found to be disrupted in the P4-ATPase AMINOPHOSPHOLIPID ATPASE 3 （ALA3）, a lipid flippase that plays a critical role in vesicle formation. We provide evidence that PEN3 undergoes continuous endocytic cycling from the PM to the trans-Golgi network （TGN）. In alp3, PEN3 accumulates in the TGN, causing delays in recruitment to the host-pathogen interface. Our results indicate that PEN3 and other defense proteins continuously cycle through the TGN and that timely exit of these proteins from the TGN is critical for effective pre-invasive immune responses against powdery mildews.

关键词： plant-microbe interactions defense responses protein traffic and secretion macromolecular trafficking papilla ABc transporter

Proteomics Technologies and challenges

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Genomics, Proteomics & Bioinformatics 2007年第2期5卷 77-85页

作者： william c.S. cho Department of clinical Oncology Queen Elizabeth Hospital

Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.

关键词： proteomics mass spectrometry, protein chip

Sublethal effects of subzero temperatures on the light brown apple moth, Epiphyas postvittana: fitness costs in response to partial freezing

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Insect Science 2019年第2期26卷 311-321页

作者： Amy c. Morey Robert c. Venette william D. Hutchison Department of Entomology University of Minnesota St. Paul Minnesota USA USDA. Forest Service Northern Research Station St. Paul Minnesota USA

Population responses to envir on mental extremes often dictate the bounds to species' distributions. However, population dynamics at, or near, those range limits may also be affected by sublethal effects. We exposed late instars and pupae of an invasive leafroller, Epiphyaspostvittana (Walker)(Lepidoptera: Tortricidae), to cold temperatures and measured the effects of exposure on subsequent survivorship, development, and reproduction. cold temperature was applied as acute exposure to -10 °c (a low, but not immediately lethal temperature for this species) or the onset of freezing (the peak of the supercooling point exotherm). Survival was defined as the ability to successfully eclose as an adult. We measured immature development times, pupal mass, and adult longevity as proxies of fitness in survivors. Additionally, surviving insects were mated with individuals that had not been exposed to cold to measure fertility. There was no difference between the proportion of larvae or pupae that survived acute exposure to -10 °c and those exposed to the control temperature. Approximately 17% of larvae and 8% of pupae survived brief periods with internal ice formation and continued development to become reproductively viable adults. Importantly, surviving the onset of freezing came with significant fitness costs but not to exposure to -10 °c;most insects that survived partial freezing had lower fertility and shorter adult lifespans than either the -10 °c or control group. These results are discussed within the context of forecasting invasive in sect distributions.

关键词： fertility invasive species partial freeze tolerance supercooling point

Magnetic systems for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2172-2196页

作者： Nicole B.Day william c.Wixson c.Wyatt Shields IV Department of chemical&Biological Engineering University of ColoradoBoulderCO 80303USA

Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional *** cell modulation through the administration of drugs,proteins,and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive *** systems offer several advantages for improving the performance of immunotherapies,including increased spatiotemporal control over transport,release,and dosing of immunomodulatory drugs within the body,resulting in reduced off-target effects and improved *** to alternative methods for stimulating drug release such as light and pH,magnetic systems enable several distinct methods for programming immune ***,we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug ***,we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target ***,we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated ***,we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor ***,we discuss translational considerations of these systems,such as toxicity,clinical compatibility,and future opportunities for improving cancer treatment.

关键词： Drug delivery Immunotherapy Magnetic hyperthermia Magnetic nanoparticles Microrobotics Biomaterials

current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology

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World Journal of clinical Oncology 2015年第6期6卷 184-188页

作者： william c Reinhold Developmental Therapeutics Branch Center for Cancer ResearchNational Cancer InstituteNational Institutes of Health

There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation,the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally,one would merge the understandability,exactness,simplicity,and testability of the molecular biological approach,with the larger amounts of data,simultaneous consideration of multiple alterations,consideration of genes both of known interest along with the novel,cross-sample comparisons among cell lines and patient samples,and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic,attempts to do so are ongoing,and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NcI-60,the Broad Institute's cancer cell Line Encyclopedia,and the Wellcome Trust Sanger Institute's cancer Genome Project,as well as the the cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research,with the desired goal being improved translational understanding and application.

关键词： Omic Molecular biology Pharmacology cancer Integration