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Nitrate reduction capacity of the oral microbiota is impaired in periodontitis:potential implications for systemic nitric oxide availability

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International Journal of Oral Science 2024年第1期16卷 52-61页

作者： Bob T.Rosier william johnston Miguel Carda-Diéguez Annabel Simpson Elena Cabello-Yeves Krystyna Piela Robert Reilly Alejandro Artacho Chris Easton Mia Burleigh Shauna Culshaw Alex Mira Department of Genomics and Health FISABIO FoundationCenter for Advanced Research in Public HealthValenciaSpain Department of Biological and Biomedical Sciences Glasgow Caledonian UniversityGlasgowUK Oral Sciences University of Glasgow Dental SchoolSchool of MedicineDentistry and NursingCollege of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowUK Sport and Physical Activity Research Institute University of the West of ScotlandBlantyreScotland Instituto de Biomedicina de Valencia Consejo Superior de Investigaciones Científicas(IBV-CSIC)ValenciaSpain CIBER Center for Epidemiology and Public Health MadridSpain

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity(NRC)and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitratereducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals(P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate(a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment(P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria(P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

关键词： impaired intake nitrate

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Treatment Patterns and Healthcare Costs among U.S. Patients with Advanced Melanoma Initiating Subsequent Systemic Therapy Following Use of Ipilimumab (IPI)

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Journal of Cancer Therapy 2016年第5期7卷 335-343页

作者： Elisabetta Malangone-Monaco Tony Okoro Beata Korytowsky Amy Stanford Stephen johnston william Johnson Sigrun Hallmeyer Truven Health Analytics Bethesda USA Bristol-Myers Squibb Princeton USA Oncology Specialists SC Park Ridge USA

As the treatment landscape for advanced melanoma continues to evolve, it is critical to focus on unmet needs and understand the cost of therapy. While Ipilimumab (IPI), an immunotherapy indicated for unresectable advanced melanoma, has been a mainstay of 1st-line treatment, there was no standard of care following progression until recently. The objective of this study was to examine real-world treatment patterns and healthcare costs following IPI use in advanced melanoma patients prior to the anti-PD-1 class approval. Adult stage III or IV melanoma patients treated with IPI were selected between April 1, 2011, and September 30, 2013, from a large U.S. commercial and Medicare claims database. Patients were evaluated for therapy after IPI, with an index date set as the first systemic therapy after IPI. Per-Patient Per-Month (PPPM) healthcare costs while on active treatment were evaluated from index until treatment discontinuation, inpatient death, end of insurance enrollment, or September 30, 2013. Of 361 eligible patients, 111 (30.7%) initiated subsequent systemic therapy (mean age, 57 years;64.9% male). The most common therapies, single-agent or combination, included vemurafenib (32.4%), paclitaxel (28.8%), temozolomide (20.7%), and carboplatin (17.1%). During a median follow-up of 130 days, mean [standard deviation] PPPM all-cause total healthcare costs were $20,383 [$18,988], of which $4800 (23.6%), $5899 (28.9%), and $9684 (47.5%) were related to melanoma drug costs, medical claims with a diagnosis of melanoma, and other (non-specified) utilization, respectively. When considering total care, the costs of U.S. patients with advanced melanoma post-IPI were substantial across all commonly used agents.

关键词： Healthcare Costs Ipilimumab Melanoma Treatment Patterns

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Efficient Gene Targeting in Maize Using Inducible CRISPR-Cas9 and Marker-free Donor Template

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Molecular Plant 2020年第8期13卷 1219-1227页

作者： Pierluigi Barone Emily Wu Brian Lenderts Ajith Anand william Gordon-Kamm Sergei Svitashev Sandeep Kumar Corteva AgriscienceTM JohnstonIA 50131USA

CRISPR-Cas9 is a powerful tool for generating targeted mutations and genomic deletions.However,precise gene insertion or sequence replacement remains a major hurdle before application of CRISPR-Cas9 technology is fully realized in plant breeding.Here,we report high-frequency,selectable marker-free intra-genomic gene targeting(GT)in maize.Heat shock-inducible Cas9 was used for generating targeted double-strand breaks and simultaneous mobilization of the donor template from pre-integratad T-DNA.The construct was designed such that release of the donor template and subsequent DNA repair activated expression of the selectable marker gene within the donor locus.This approach generated up to 4.7%targeted insertion of the donor sequence into the target locus in TO plants,with up to 86%detected donor template release and 99%mutation rate being observed at the donor loci and the genomic target site,respectively.Unlike previous in planta or intra-genomic homologous recombination reports in which the original chimeric GT plants required extensive progeny screening in the next generation to identify non-chimeric GT individuals,our method provides non-chimeric heritable GT in one generation.

关键词： donor template insertion

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Method Development for the Detection of Basic/Weak Basic Drugs in Hair by LCMSMS: Comparison between Methanolic and Alkaline Extraction on Real Samples

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Pharmacology & Pharmacy 2012年第3期3卷 263-274页

作者： Jaber Al Jaber David Holt Atholl johnston Analytical Services International Ltd St George’s University of London UK The william Harvey Research Institute Barts & The London School of Medicine & Dentistry Queen Mary University of London UK

Detection of drugs in hair has become popular in recent years. The significantly long drug detection window (months) in hair has allowed the retrospective investigation and measurement of past consumption of drug. As the majority of drugs are basic, an extraction method was developed based on a methanolic solution for detection of basic/weak basic drugs in hair. It was compared with alkaline digestion (NaOH) followed by LLE. A filtration step with filtration vials was added and their materials were compared. After filtration, extracts were injected directly onto a C18 column coupled to Sciex ABI 2000 MSMS. The mobile phase was 50% methanol, 0.1% formic acid and 2 mM ammonium acetate (isocratic). Both methods were compared by applying them to real samples. Results showed that calibration was linear with r2 of 0.991-0.999 for 20 tested analytes. The matrix effect was assessed to be between 91.4%- 110.2% for 18 analytes. PTFE filter material showed better recoveries over the GMF and PVDF based filters. Stability of analytes during extraction in general was better with methanolic incubation rather than alkaline digestion. With regard to real sample recovery, 6 out of 10 analytes recovered better with alkaline digestion. In conclusion, the methanolic method is capable of extracting most basic drugs in hair samples but only part of the total incorporated drug. Therefore, these results suggest that a combination of both methods (methanolic and alkaline extractions) in hair sample processing for general detection of basic and weak basic drugs may produce better results. However, not all basic drugs are stable under alkaline digestion.

关键词： Hair Analysis Basic Drugs LCMSMS Benzodiazepines Method Development LLE

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现代机载预警雷达

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电子对抗技术 1991年第3期6卷 30-35页

作者： william C.Morchin Stephen L.johnston 吕连元

机载预警雷达(AEW)由二战中使用的AN/APS-20发展而来,战后近五十年来,AEW雷达获得了飞速发展。该文先描述一下AEW系统,而后对其进行一番评述,并对40种AEW雷达的主要性能都列了表。由于现代AEW雷达通常包含第二种工作模式,所以文中包括... 详细信息

机载预警雷达(AEW)由二战中使用的AN/APS-20发展而来,战后近五十年来,AEW雷达获得了飞速发展。该文先描述一下AEW系统,而后对其进行一番评述,并对40种AEW雷达的主要性能都列了表。由于现代AEW雷达通常包含第二种工作模式,所以文中包括一些用于战场监视和海面搜索的AEW雷达,作为补充描述英性能的例子。

关键词：机载雷达预警雷达雷达

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超越创造共享价值:品格决定公司命运

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中国社会组织 2015年第16期 44-45页

作者： Julian Gresser Patricia Bader-johnston william Moulton 高正

在世界各地,公司的管理职责作为开明经营的一个原则正日益受到认可。一个公司或企业不再仅被视为一个可以任由其所有者和管理者为所欲为的孤立自主的个体。公司具有双重角色：一方面,要为其股东提供优越的回报;另一方面,它同时也要承担... 详细信息

在世界各地,公司的管理职责作为开明经营的一个原则正日益受到认可。一个公司或企业不再仅被视为一个可以任由其所有者和管理者为所欲为的孤立自主的个体。公司具有双重角色：一方面,要为其股东提供优越的回报;另一方面,它同时也要承担对经济、社会与环境的责任。在更完备的＂综合财务报表＂中体现出的向＂第四代领导力＂（即互惠管理）的过渡等理念,正在加快主流观点接受这一核心假设，即公司价值观与社会公益能够其同提供一条通往可持续发展的未来的途径。

关键词：共享价值综合财务会计程序竞争力指标谈判能力供应链财务分析持续增长数据分析能力双重角色

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Attitudes towards acceptance of an innovative home-based and remote sensing rehabilitation protocol among cardiovascular patients in Shantou, China

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Journal of Geriatric Cardiology 2016年第4期13卷 326-332页

作者： Jia-Ying FANG Ji-Linm LI Zhong-Han LI Duan-Min XU Chang CHEN Bin XIE Helen CHEN william W AU Department of Preventive Medicine Shantou University Medical College Shantou China Department of Cardiology the First Affiliated Hospital of Shantou University Medical College Shantou China School of Public Health and Health Systems University of Waterloo Waterloo Canada

BackgroundCardiac 康复(CR ) 协议有对多样化作为基于医院或基于中心的 CR 的一种选择包括本垒的心脏的电视康复(HBCTR ) 。采用本垒的心脏的电视康复的使用，向如此的电子健康技术的接受估计心脏病患者态度是必要的，特别在如此的技... 详细信息

BackgroundCardiac 康复(CR ) 协议有对多样化作为基于医院或基于中心的 CR 的一种选择包括本垒的心脏的电视康复(HBCTR ) 。采用本垒的心脏的电视康复的使用，向如此的电子健康技术的接受估计心脏病患者态度是必要的，特别在如此的技术的知识的中国， deficient.MethodsInterviews 在 Shantou 大学医学院的首先隶属于的医院里被进行， Shantou，中国。在经皮的冠的 interventional (一种总线标准) 以后外科，病人们完成了 survey.ResultsAmong 150 个病人，仅仅， 13% 曾经听说了 HBCTR。在我们的 HBCTR 节目的介绍以后， 60% 病人愿意参予节目。从我们问询表数据的 multivariate 分析，变老(或：0.92， 95% CI：0.86-0.98；P = 0.007 ) ，普通家庭月刊收入(或：0.13， 95% CI：0.05-0.34；P <；0.001 ) ，教育水平(或：0.24， 95% CI：0.10-0.59；P = 0.002 ) 并且 physical ；锻练时间(或：0.19， 95% CI：0.06-0.56；P = 0.003 ) 是为 HBCTR 的接受的独立预言者。从为参予的原因，病人们选择了：提高的安全和独立(28.3%) ，自我监视器的能力物理条件日报(25.4%) ，并且有自动并且紧急情况警戒(23.1%) 。推理因为拒绝：太拖累的操作(34.3%) 和不必要的协议(19.4%).ConclusionsMost 病人关于 HBCTR 缺乏知识，但是在他们了解了节目以后，自愿参与。几个个人和生活方式因素影响了他们节目的接受。这些显示两个都，技术的改进和节目的更好的理解将提高活跃参予。

关键词：汕头市患者康复中国协议心血管可信区间遥感

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Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma

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Journal of Cancer Therapy 2013年第8期4卷 1298-1305页

作者： Ana I. Velazquez David J. Inwards Stephen M. Ansell Ivana N. Micallef Patrick B. johnston william J. Hogan Svetomir N. Markovic Luis F. Porrata Division of Hematology Department of Internal Medicine Mayo Clinic Rochester USA

Day 100 prognostic factors post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients have not been studied. Thus, we retrospectively examined if day 100 absolute monocyte/lymphocyte prognostic score (AMLPS-100) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT in DLBCL. Only DLBCL patients in complete remission at day 100 post-APBHSCT were evaluated. From 2000 to 2007, 134 consecutive DLBCL patients are qualified for the study. Patients with a day 100 absolute monocyte count (AMC-100) ≥ 630 cells/μL and day 100 absolute lymphocyte count (ALC-100) ≤ 1000 cells/μL experienced inferior overall survival (OS) and progression free survival (PFS). On multivariate analysis, the AMC-100 and ALC-100 remained independent predictors of OS and PFS. Combining both values into the AMLPS-100, the 5-year OS rates for low, intermediate, and high AMLPS-100 risk groups were 94% (95% CI, 83.0% - 98.1%), 70% (95% CI, 58.6% - 80.1%), and 13% (95% CI, 3.4% - 40.5%), respectively;and the 5-year PFS rates were 87% (95% CI, 74.0% - 94.1%), 68% (95% CI, 56.0% - 77.8%), and 13% (95% CI, 3.4% - 40.5%), respectively. The AMLPS-100 is a simple biomarker score that can stratify clinical outcomes from day 100 post-APBHSCT in DLBCL patients.

关键词： Monocyte/Lymphocyte Prognostic Score Diffuse Large B-Cell Lymphoma Survival Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

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2015年美国心脏协会／美国卒中协会对2013年急性缺血性卒中患者早期处理指南关于血管内治疗的局部更新

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国际脑血管病杂志 2015年第11期23卷 801-814页

作者：蔡必扬李华代齐良徐格林南京军区南京总医院神经内科 210002

目的本指南旨在对急性缺血性卒中血管内治疗的现有推荐意见提供局部更新。如相关内容与上一版指南重叠，则以本指南的推荐意见为准。方法此次局部更新对2013年以来发表的8项有关血管内治疗的临床随机试验结果和其他相关资料进行了分析... 详细信息

目的本指南旨在对急性缺血性卒中血管内治疗的现有推荐意见提供局部更新。如相关内容与上一版指南重叠，则以本指南的推荐意见为准。方法此次局部更新对2013年以来发表的8项有关血管内治疗的临床随机试验结果和其他相关资料进行了分析。本文并未对上一版指南发布后的所有文献进行全面回顾，而仅仅纳入了支持对现有推荐意见进行修改的关键性新证据。指南撰写委员会成员由美国心脏协会（American Heart Association，AHA）／美国卒中协会（American Stroke Association，ASA）卒中委员会下属的科学声明监督委员会以及AHA／ASA文稿监督委员会任命。整个指南制定过程严格遵守AHA的利益冲突政策。采用美国心脏协会，美国卒中协会的疗效确定性水平和证据分级方案对推荐意见进行分级。由6名同行评议专家以及卒中委员会科学声明监督委员会和卒中委员会领导委员会成员对指南草案进行发表前审阅。结果本循证指南介绍了急性缺血性卒中血管内治疗的患者选择、操作规程以及促进血管内治疗的医疗体系。结论某些血管内介入操作被证明能够为经过选择的急性缺血性卒中患者提供临床益处，应组建相应的医疗体系以促进血管内治疗的开展。

关键词： AHA科学声明血管内介入治疗动脉内输注神经影像学支架卒中治疗学

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Highlights of the 2nd International Symposium on Tribbles and Diseases: tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

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Acta Pharmaceutica Sinica B 2019年第2期9卷 443-454页

作者： Bing Cui Patrick A. Eyers Leonard L. Dobens Nguan Soon Tan Peter D. Mace Wolfgang A. Link Endre Kiss-Toth Karen Keeshan Takuro Nakamura Warren S. Pear Yodit Feseha Jessica johnston Arkatiz Carracedo Marcel Scheideler Zabran llyas Robert C. Bauer Jorge D. Erusalimsky Dominika Grzesik Juan Salamanca-Viloria Xiaoxi Lv Yishi Jin Ke Li Guillermo Velasco Shuang Shang Jose M. Lizcano Xiaowei Zhang Jichao Zhou Jiaojiao Yu Fang Hua Feng Wang Shanshan Liu Jinmei Yu Zhuowei Hu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Department of Biochemistry Institute of Integrative Biology University of Liverpool Division of Molecular Biology and Biochemistry School of Biological Sciences University of Missouri-Kansas City School of Biological Sciences Nanyang Technological University Lee Kong Chian School of Medicine Nanyang Technological University Institute of Molecular and Cell Biology KK Women's and Children Hospital Biochemistry Department School of Biomedical Sciences University of Otago Centre for Biomedical Research (CBMR) University of Algarve Campus de Gambelas Department of Biomedical Sciences and Medicine University of Algarve Algarve Biomedical Center (ABC) University of Algarve Campus de Gambelas Department of Infection Immunity and Cardiovascular Disease University of Sheffield Paul O'Gorman Leukaemia Research Centre Institute of Cancer Sciences University of Glasgow Division of Carcinogenesis The Cancer Institute Japanese Foundation for Cancer Research Department of Pathology and Laboratory Medicine Abramson Family Cancer Research Institute Perelman School of Medicine at the University of Pennsylvania Centre de Recherche en Transplantation et Immunologie (ou CRTI) Inserm Université de Nantes Nantes France Institut de Transplantation Urologie Néphrologie (ou ITUN) CIC bioGUNE CIBERONC Ikerbasque Basque Foundation for Science Biochemistry and Molecular Biology Department University of the Basque Country (UPV/EHU) Institute for Diabetes and Cancer IDC Helmholtz Center Munich Joint Heidelberg-IDC Translational Diabetes Program University Hospital Heidelberg Molecular Metabolic Control Medical Faculty Technical University Munich German Center for Diabetes Research (DZD) Division of Cardiology Department of Medicine Columbia University Irving Medical Center School of Sport and Health Sciences Cardiff Metropolitan Universit

The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.

关键词： Tribbles Immunology Metabolism Cell biology Kinase inhibitor Tumorigenesis Metastasis TRIB1 TRIB2 TRIB3 Pseudokinase Inflammation Atomic structure Protein quality control Ubiqutin

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