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Diabetes Mellitus and Colorectal Neoplasia

Journal of Cancer Therapy 2012年第6期3卷 859-865页

作者： Alejandro Acevedo Yaritza Diaz Cynthia M. Perez Maria Garau john baron Marcia Cruz-Correa Department of Biostatistics and Epidemiology Graduate School of Public Health Medical Sciences Campus University of Puerto Rico San Juan Puerto Rico Department of Medicine Community and Family Medicine Dartmouth Medical School Dartmouth US Department of Medicine Community and Family Medicine Dartmouth Medical School Hanover USA Department of Medicine School of Medicine University of Puerto Rico San Juan Puerto Rico University of Puerto Rico Comprehensive Cancer Center San Juan Puerto Rico

Background: Many studies have provided evidence for an association between obesity, physical inactivity, and western diet as risk factors for colorectal cancer (CRC). Few studies directly address the association between type 2 Diabetes Mellitus (DM) and the risk of colorectal lesions at specific anatomic locations. Methods: 2663 subjects with a previous history of adenoma (s) and removal of all current adenomas at study entry were followed for a mean time of three years across three different chemoprevention clinical trials. The primary endpoint was colorectal adenoma recurrence and number of lesions during the treatment phase;the secondary endpoints were presence of advanced colorectal neoplasia (CRN) and location of CRN. Using log linear regression, the effect of DM status on the relative risk (RR) of CRN recurrence, advanced CRN, and location of CRN was assessed. Results: DM status was not significantly associated with incidence of colorectal adenomas, incidence of advanced colorectal lesions, or left-sided colorectal neoplastic lesions. Subjects with DM had a marginally increased risk of right-sided (p = 0.06) colorectal adenomas and a significant increased risk of multiple right-sided adenomas (p = 0.03) in the unadjusted model;this association was not significant after adjusting for age and other potential confounders (RR = 1.22, 95% CI: 0.85 - 1.76). Conclusion: We did not observe a statistically significant increased risk in CRN recurrence for overall neoplasia, advanced neoplasia or location of neoplasia in individuals with DM compared to non-DM individuals. However, given the patterns observed in this investigation, future studies with longer follow-up time and longer DM exposure, incorporating objective measurements of type 2 DM might help elucidate the risk of CRN among individuals with DM.

关键词： Diabetes Mellitus Colorectal Neoplasia Colorectal Adenomas Chemoprevention

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Development and validation of a registry-based definition of eosinophilic esophagitis in Denmark

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World Journal of Gastroenterology 2013年第4期19卷 503-510页

作者： Evan S Dellon Rune Erichsen Lars Pedersen Nicholas J Shaheen john A baron Henrik T Sφrensen Mogens Vyberg Center for Esophageal Diseases and Swallowing and Center for Gastrointestinal Biology and DiseaseDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of North Carolina School of MedicineChapel HillNC 27599-7080United States Center for Gastrointestinal Biology and Disease Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of North Carolina School of MedicineChapel HillNC 27599-7080United States Department of Clinical Epidemiology Aarhus University Hospital8000 AarhusDanmark Institute of Pathology Aalborg HospitalAarhus University Hospital8000 AarhusDanmark

AIM:To develop and validate a case definition of eosinophilic esophagitis(EoE) in the linked Danish health ***:For case definition development,we queried the Danish medical registries from 2006-2007 to identify candidate cases of EoE in Northern *** International Classification of Diseases-10(ICD-10) and prescription codes were obtained,and archived pathology slides were obtained and re-reviewed to determine case *** used an iterative process to select inclusion/exclusion codes,refine the case definition,and optimize sensitivity and *** then re-queried the registries from 2008-2009 to yield a validation *** case definition algorithm was applied,and sensitivity and specificity were ***:Of the 51 and 49 candidate cases identified in both the development and validation sets,21 and 24 had EoE,*** of EoE cases in the development set [mean age 35 years;76% male;86% dysphagia;103 eosinophils per high-power field(eos/hpf)] were similar to those in the validation set(mean age 42 years;83% male;67% dysphagia;77 eos/hpf).Re-review of archived slides confirmed that the pathology coding for esophageal eosinophilia was correct in greater than 90% of *** registrybased case algorithms based on pathology,ICD-10,and pharmacy codes were successfully generated in the development set,one that was sensitive(90%) and one that was specific(97%).When these algorithms were applied to the validation set,they remained sensitive(88%) and specific(96%).CONCLUSION:Two registry-based definitions,one highly sensitive and one highly specific,were developed and validated for the linked Danish national health databases,making future population-based studies feasible.

关键词： Eosinophilic esophagitis Denmark Epidemiology Case definition Sensitivity Specificity

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Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry

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World Journal of Gastroenterology 2013年第21期19卷 3241-3248页

作者： Scott V Adams Dennis J Ahnen john A baron Peter T Campbell Steven Gallinger William M Grady Loic LeMarchand Noralane M Lindor john D Potter Polly A Newcomb Cancer Prevention Public Health SciencesFred Hutchinson Cancer Research CenterSeattleWA 98109United States Department of Medicine Denver VA Medical Center and University of Colorado School of MedicineDenverCO 80045United States Department of Medicine University of North CarolinaChapel HillNC 27599United States Epidemiology Research Program Department of Intramural ResearchAmerican Cancer SocietyAtlantaGA 30303United States Division of General Surgery University of TorontoTorontoON M5G2C4Canada Cancer Research Center of Hawaii University of HawaiiHonoluluHI 96813United States Department of Health Science Research Mayo Clinic ArizonaScottsdaleAZ 85259United States

AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.

关键词： Colorectal cancer Inflammatory bowel disease Outcomes research Cancer survival Inflammation

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Subcutaneous fatty acid composition of steers finished as weanlings or yearlings with and without growth promotants

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Journal of Animal Science and Biotechnology 2014年第1期5卷 98-105页

作者： Cletos Mapiye Tyler D Turner john A Basarab Vern S baron Jennifer L Aalhus Michael ER Dugan Agriculture and Agri-Food Canada Lacombe Research Centre 6000 C & E Trail Lacombe Alberta T4L 1 W1 Canada Alberta Agriculture and Rural Development Lacombe Research Centre 6000 C & E Trail Lacombe Alberta T4L 1 W1 Canada

Background： The current study evaluated the subcutaneous fatty acid （FA） composition of calf- and yearling-fed steer with or without growth promoting implants. Crossbred steers （n = 112; 267 ± 5.0 kg） of the same contemporary group were allocated to one of four production system and implant strategy based treatments in a completely randomized design with a 2 × 2 factorial arrangement of treatments. Results： There were no interactions （P 〉 0.05） between production systems and growth promoting implants for the total and individual subcutaneous FA. Yearling as opposed to calf finishing reduced （P 〈 0.05） subcutaneous proportions of C20：3n-6, trans （t）l 2-18：1, C14：0, several minor cis-monounsaturated FA （c-MUFA; c9-14：1, c11-16：1, cl 1-18：1, cl 2-18：1, cl 3-18：1, c9-20：1 and cl 1-20：1）, and increased （P 〈 0.05） subcutaneous proportions of tl 1 cl 5-18：2, total and individual branched-chain FA. Subcutaneous fat from steers implanted with growth promotants had higher （P 〈 0.05） proportions of total polyunsaturated FA （PUFA）, total n-6 PUFA, C18：2n-6 and individual t-18：1 isomers （t6 to tl0） compared to non-implanted steers. Conclusions： Overall, current findings show that production systems and growth promotants led to only minor differences in subcutaneous FA composition of beef steers.

关键词： Age at feedlot entry Beef Fatty acids Growth implant Steers

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上消化道疾病基础知识(三) 胃十二指肠溃疡和胃癌的病理生理

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英国医学杂志中文版 2003年第2期6卷 101-104页

作者： john Calam JH baron 王玉珍 professor of gastroenterology at Imperial College School of Medicine.

胃十二指肠溃疡和胃癌是常见的严重疾病,在感染幽门螺杆菌的人群中,只有少数人才会发病。由于需要资金的投入并且有导致耐药的危险,大规模地根除幽门螺杆菌是不现实的。而掌握幽门螺杆菌导致溃疡和胃癌形成机制方面的知识是很重要的。 ... 详细信息

胃十二指肠溃疡和胃癌是常见的严重疾病,在感染幽门螺杆菌的人群中,只有少数人才会发病。由于需要资金的投入并且有导致耐药的危险,大规模地根除幽门螺杆菌是不现实的。而掌握幽门螺杆菌导致溃疡和胃癌形成机制方面的知识是很重要的。很多因素影响幽门螺杆菌感染的结局,包括宿主反应。

关键词：上消化道疾病基础知识胃十二指肠溃疡胃癌病理生理胃酸分泌幽门螺杆菌

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Author Correction: Disrupted Ca2+ homeostasis and immunodeficiency in patients with functional IP3 receptor subtype 3 defects

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Cellular & Molecular Immunology 2023年第1期20卷 114-114页

作者： Julika Neumann Erika Van Nieuwenhove Lara E.Terry Frederik Staels Taylor R.Knebel Kirsten Welkenhuyzen Kourosh Ahmadzadeh Mariah R.Baker Margaux Gerbaux Mathijs Willemsen john S.Barber Irina I.Serysheva Liesbeth De Waele François Vermeulen Susan Schlenner Isabelle Meyts David I.Yule Geert Bultynck Rik Schrijvers Stephanie Humblet-baron Adrian Liston VIB Center for Brain and Disease Research Leuven Belgium (GRID:grid.511015.1) KU Leuven Department of Microbiology and Immunology Leuven Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) VIB Center for Brain and Disease Research Leuven Belgium (GRID:grid.511015.1) KU Leuven Department of Microbiology and Immunology Leuven Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) UZ Leuven Leuven Belgium (GRID:grid.410569.f) (ISNI:0000 0004 0626 3338) University of Rochester Department of Pharmacology and Physiology Rochester USA (GRID:grid.16416.34) (ISNI:0000 0004 1936 9174) KU Leuven Department of Microbiology and Immunology Leuven Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) UZ Leuven Leuven Belgium (GRID:grid.410569.f) (ISNI:0000 0004 0626 3338) Leuven Kankerinstituut KU Leuven Laboratory of Molecular and Cellular Signaling Department of Cellular and Molecular Medicine Leuven Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) Rega Institute KU Leuven Laboratory of Immunobiology Department Microbiology and Immunology Leuven Belgium (GRID:grid.415751.3) McGovern Medical School at The University of Texas Health Science Center at Houston Department of Biochemistry and Molecular Biology Structural Biology Imaging Center Houston USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401) KU Leuven Department of Microbiology and Immunology Leuven Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) Academic Children Hospital Queen Fabiola Université Libre de Bruxelles Pediatric Department Brussels Belgium (GRID:grid.4989.c) (ISNI:0000 0001 2348 0746) University Hospitals Leuven Department of Pediatric Neurology Leuven Belgium (GRID:grid.410569.f) (ISNI:0000 0004 0626 3338) University Hospitals Leuven Department of Pulmonology Leuven Belgium (GRID:grid.410569.f) (ISNI:0000 0004 0626 3338) KU Leuven Department of Microbiology and Immunology Leuven Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) UZ Leuven Leuven Belgium (GRID:grid.410569.f) (ISNI:0000 0004

In this article the statement in the Acknowledgements section was incorrectly given as “MRB and IIS are supported by the NIH R01GM080139 grant (to IIS), the Welch Foundation Research Grant AU-2014-20190331 (to IIS), and the American Heart Association grant 18CDA34110086 (to MRB)” and should have been, “MRB and IIS are supported by the NIH R01GM072804 grant (to IIS), the Welch Foundation Research Grant AU-2014-20190331 (to IIS), and the American Heart Association grant 18CDA34110086 (to MRB).”

关键词： IIS statement knowledge

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Disrupted Ca^(2+) h homeostasis and immunodeficiency in patients with functional IP_(3) receptor subtype 3 defects

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Cellular & Molecular Immunology 2023年第1期20卷 11-25页

Calcium signaling is essential for lymphocyte activation, with genetic disruptions of store-operated calcium (Ca^(2+)) entry resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP_(3)R), a homo- or heterotetramer of the IP_(3)R1-3 isoforms, amplifies lymphocyte signaling by releasing Ca^(2+) from endoplasmic reticulum stores following antigen stimulation. Although knockout of all IP_(3)R isoforms in mice causes immunodeficiency, the seeming redundancy of the isoforms is thought to explain the absence of variants in human immunodeficiency. In this study, we identified compound heterozygous variants of ITPR3 (a gene encoding IP_(3)R subtype 3) in two unrelated Caucasian patients presenting with immunodeficiency. To determine whether ITPR3 variants act in a nonredundant manner and disrupt human immune responses, we characterized the Ca^(2+) signaling capacity, the lymphocyte response, and the clinical phenotype of these patients. We observed disrupted Ca^(2+) signaling in patient-derived fibroblasts and immune cells, with abnormal proliferation and activation responses following T-cell receptor stimulation. Reconstitution of IP_(3)R3 in IP_(3)R knockout cell lines led to the identification of variants as functional hypomorphs that showed reduced ability to discriminate between homeostatic and induced states, validating a genotype–phenotype link. These results demonstrate a functional link between defective endoplasmic reticulum Ca^(2+) channels and immunodeficiency and identify IP_(3)Rs as diagnostic targets for patients with specific inborn errors of immunity. These results also extend the known cause of Ca^(2+)-associated immunodeficiency from store-operated entry to impaired Ca^(2+) mobilization from the endoplasmic reticulum, revealing a broad sensitivity of lymphocytes to genetic defects in Ca^(2+) signaling.

关键词： Primary immunodeficiency Calcium signalling Whole exome sequencing

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约克圣约翰大学创意中心

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现代装饰 2022年第5期 132-137页

作者： MGACI RLF Eduardo Andreu Gonz a lez Rob baron Amir Daryoushnezhad Finbarr Duerden Caroline Dunham Rory Harmer Jolene Hor Qaisy Jaslenda laia Loppi Amber McLaren Simon Munashe Dendere Laurence Pinn Ed Rawle Mohammed Syafig B Hassan Jubri Tristan Searight Jerry Tate Atelier Ten Atelier One Colour Hufton+Crow(摄影) 舒禹(编译) 不详

近期,由Tate+Co Architects设计的约克圣约翰大学创意中心已向学生敞开大门。这座低能耗建筑为约克圣约翰大学的音乐和计算机专业课程提供永久新家,也为表演、创意写作,和媒体制作专业的学生提供空间。项目由三个主要概念构成,首先,这... 详细信息

近期,由Tate+Co Architects设计的约克圣约翰大学创意中心已向学生敞开大门。这座低能耗建筑为约克圣约翰大学的音乐和计算机专业课程提供永久新家,也为表演、创意写作,和媒体制作专业的学生提供空间。项目由三个主要概念构成,首先,这是一座真正的可持续的建筑,它有着坚固的木结构,无论是在运营方面还是在隐含碳方面都是可持续的。其次,主中庭空间的建筑元素体现了高等教育中创造跨学科合作的“第三空间”思想。最后,该中心充分利用靠近约克大教堂的地理位置优势,将大学与周边城市连接起来,在整个中庭、演奏厅和听音室中,为令人惊叹的历史遗址更添如西景色。

关键词：低能耗建筑建筑元素中庭空间圣约翰大学地理位置优势木结构媒体制作第三空间

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