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World Journal of Gastroenterology 2013年第21期19卷 3347-3351页

作者： Christopher Ma Brennan Walters richard n Fedorak Division of Gastroenterology University of AlbertaEdmontonAL T6G 2X8Canada

Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TnF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TnF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TnF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TnF therapy.

关键词： Varicella zoster virus Meningitis Crohn’s disease Adalimumab Infliximab corticosteroids Antitumor necrosis factor

novel design concepts for network intrusion systems based on dendritic cells processes

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Journal of Central South University 2013年第8期20卷 2175-2185页

作者： richard M R 谭冠政 OnGALO P n F CHERUIYOT W School of Information Science and Engineering Central South University

An abstraction and an investigation to the worth of dendritic cells (DCs) ability to collect, process and present antigens are presented. Computationally, this ability is shown to provide a feature reduction mechanism that could be used to reduce the complexity of a search space, a mechanism for development of highly specialized detector sets as well as a selective mechanism used in directing subsets of detectors to be activated when certain danger signals are present. It is shown that DCs, primed by different danger signals, provide a basis for different anomaly detection pathways. Different antigen-peptides are developed based on different danger signals present, and these peptides are presented to different adaptive layer detectors that correspond to the given danger signal. Experiments are then undertaken that compare current approaches, where a full antigen structure and the whole repertoire of detectors are used, with the proposed approach. Experiment results indicate that such an approach is feasible and can help reduce the complexity of the problem by significant levels. It also improves the efficiency of the system, given that only a subset of detectors are involved during the detection process. Having several different sets of detectors increases the robustness of the resulting system. Detectors developed based on peptides are also highly discriminative, which reduces the false positives rates, making the approach feasible for a real time environment.

关键词： artificial immune systems network intrusion detection anomaly detection feature reduction negative selectionalgorithm danger model

Distance management of inflammatory bowel disease:Systematic review and meta-analysis

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World Journal of Gastroenterology 2014年第3期20卷 829-842页

作者： Vivian W Huang Krista M Reich richard n Fedorak Division of Gastroenterology University of Alberta

AIM: To review the effectiveness of distance management methods in the management of adult inflammatory bowel disease (IBD) patients.

关键词： Telemanagement Telehealth Inflammatory bowel disease Distance management Self-management

Impact of the polymer backbone chemistry on interactions of amino-acid-derived zwitterionic polymers with cells

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Bioactive Materials 2023年第6期24卷 524-534页

作者： Meike n.Leiske Bruno G.De Geest richard Hoogenboom Supramolecular Chemistry Group Centre of Macromolecular Chemistry(CMaC)Department of Organic and Macromolecular ChemistryGhent UniversityKrijgslaan 281 S4B-9000GhentBelgium Department of Pharmaceutics and Cancer Research Institute Ghent(CRIG) Ghent UniversityOttergemsesteenweg 460B-9000GhentBelgium Faculty of Biology Chemistry&Earth SciencesUniversity of BayreuthUniversitätsstraße 3095447 BayreuthGermany

Zwitterionic polymers are known to interact with cells and have been shown to reveal cancer cell *** this work,the importance of the chemistry of the polymer backbone for the cellular specificity of amino-acid-derived polyzwitterions is demonstrated.A series of glutamic acid(Glu)-based vinyl monomers(i.e.,an acrylate,a methacrylate,an acrylamide,and a methacrylamide)were prepared and used for reversible addition-fragmentation chain-transfer(RAFT)polymerisation,yielding defined polymers with narrow size distribution(Ðnctionalised,zwitterionic polymers revealed high cytocompatibility;however,differences in cellular association and specificity were *** particular,the methacrylamide-derived polymers showed high association with both,breast cancer cells and non-cancerous dendritic cells and,consequently,lack *** contrast,high specificity to only breast cancer cells was observed for polyacrylates,-methacrylates,*** analysis of the polymers revealed differences in hydrophobicity,zeta potential,and potential side chain hydrolysis,which are impacted by the polymer backbone and might be responsible for the altered the cell association of these *** is shown that a slightly negative net charge is preferred over a neutral charge to retain cell *** was also confirmed by association experiments in the presence of competitive amino acid transporter *** affinity of slightly negatively charged Glu-derived polymers to the xCT Glu/cystine cell membrane antiporter was found to be higher than that of neutrally charged *** results emphasise the importance of the polymer backbone for the design of cell-specific *** study further highlights the potential to tailor amino-acid-derived zwitterionic materials beyond their side chain functionality.

关键词： Amino-acid-functionalised polymer Zwitterionic polymer Cell-specific polymer Cancer-targeting RAFT-Polymerisation

Long-term esophageal and respiratory outcomes in children with esophageal atresia and tracheoesophageal fistula

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Gastroenterology Report 2016年第4期4卷 310-314,I0002页

作者： richard H.Cartabuke Rocio Lopez Prashanthi n.Thota Department of Internal Medicine Cleveland ClinicClevelandOHUSA Department of Biostatistics Cleveland ClinicClevelandOHUSA Department of Gastroenterology and Hepatology Cleveland ClinicClevelandOHUSA

Objectives:Few studies have evaluated the long-term complications and outcomes of esophageal atresia with or without tracheoesophageal fistula(EA/TEF)beyond *** aim of our study was to characterize the esophageal and respiratory morbidity of EA/TEF through evaluation of clinical symptoms,diagnostic testing and therapeutic intervention at a tertiary care ***:Patients with congenital EA/TEF evaluated from 2011 to 2014 were *** characteristics,type and mode of repair of EA/TEF,clinical symptoms,radiographic,endoscopic,bronchoscopic and medication use data were ***:A total of 43 patients were *** median age of this predominantly Caucasian population was 8 years(interquartile range:3,20).Twenty(62.5%)had type C(EA with distal TEF)***-one(48.8%)patients had heartburn,19(44.1%)had acid regurgitation,and 31(72.1%)had dysphagia to *** swallow in 26 patients revealed strictures in 17(65.4%),dysmotility in 20(76.9%)and recurrent fistulas in four patients(15.4%).Thirty patients underwent upper endoscopy,of which 21(70.0%)had a stricture,and six(20.0%)had recurrent fistula requiring surgical ***(18.6%)patients underwent *** evaluation showed cough and choking in 31(72.1%)patients and dyspnea and wheezing in 32(53.4%)*** respiratory infections were reported in 19(44.2%).*** findings included tracheomalacia in 86.7% and restrictive lung disease in 54.5%of ***:There is a high burden of residual esophageal and pulmonary pathology in patients with EA/*** follow-up is required to monitor both the clinical symptoms and treatment responses.

关键词： esophageal atresia tracheoesophageal fistula gastroesophageal reflux disease(GERD) esophageal dysmotility aspiration pneumonia

Translational pain research: Evaluating analgesic effect in experimental visceral pain models

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World Journal of Gastroenterology 2009年第2期15卷 177-181页

作者： Anne Estrup Olesen Trine Andresen Lona Louring Christrup richard n Upton Mech-Sense Department of Gastroenterology Aalborg Hospital Aarhus University Hospital 9000 Aalborg Denmark Center for Sensory-Motor Interactions Department of Health Science and Technology Aalborg University 9000 AalborgDenmark Center for Sensory-Motor Interactions Department of Health Science and Technology Aalborg University 9000 Aalborg Denmark Faculty of Pharmaceutical Sciences University of Copenhagen Denmark Discipline of Anaesthesia and Intensive Care Royal Adelaide Hospital University of Adelaide Adelaide South Australia Australia

Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can be achieved through stand-ardized experimental human pain models. Experimental pain models in healthy volunteers are advantageous for evaluation of analgesic action, as this is often diff icult to assess in the clinic because of confounding factors such as sedation, nausea and general malaise. These pain models facilitate minimizing the gap between knowledge gained in animal and human clinical studies. Combining experimental pain studies and pharmacokinetic stud- ies can improve understanding of the pharmacokinetic-pharmacodynamic relationship of analgesics and, thus, provide valuable insight into optimal clinical treatment of visceral pain. To improve treatment of visceral pain, it is important to study the underlying mechanisms of pain and the action of analgesics used for its treatment. An experimental pain model activates different modalities and can be used to investigate the mechanism of action of different analgesics in detail. In combination with pharmacokinetic studies and objective assessment such as electroencephalography, new information re-garding a given drug substance and its effects can be obtained. Results from experimental human visceral pain research can bridge the gap in knowledge between animal studies and clinical condition in patients suffering from visceral pain, and thus constitute the missing link in translational pain research.

关键词： Visceral pain Analgesics Pharmacokinetics Pharmacodynamics

Choledochal cysts: Similarities and differences between Asian and Western countries

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World Journal of Gastroenterology 2019年第26期25卷 3334-3343页

作者： George n Baison Morgan M Bonds William S Helton richard A Kozarek Digestive Disease Institute Virginia Mason Medical Center

Choledochal cysts(CCs)are rare bile duct dilatations,intra-and/or extrahepatic,and have higher prevalence in the Asian population compared to Western *** of the current literature on CC disease originates from Asia where these entities are most *** are thought to arise from an anomalous pancreaticobiliary junction,which are congenital anomalies between pancreatic and bile *** similarities in presentation between Eastern and Western patients exist such as female predominance,however,contemporary studies suggest that Asian patients may be more symptomatic on *** though CC disease presents with an increased malignant risk reported to be more than 10%after the second decade of life in Asian patients,this risk may be overstated in Western *** this difference in cancer risk,management guidelines for all patients with CC are based predominantly on observations reported from Asia where it is recommended that all CCs should be excised out of concern for the presence or development of biliary tract cancer.

关键词： Choledochal cyst Cholangiocarcinoma Asian populations Western populations Anomalous pancreaticobiliary junction

Vitamin D improves inflammatory bowel disease outcomes:Basic science and clinical review

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World Journal of Gastroenterology 2014年第17期20卷 4934-4947页

作者： Krista M Reich richard n Fedorak Karen Madsen Karen I Kroeker Division of Gastroenterology University of AlbertaEdmontonAlberta T6G 2X8Canada

Vitamin D deficiency is commonly diagnosed among patients with inflammatory bowel disease (IBD). Patients with IBD are at risk of low bone density and increased fractures due to low vitamin D levels, long standing disease, and frequent steroid exposures; as a result, it is well established that vitamin D supplementation in this population is important. There is increasing support for the role of vitamin D in strengthening the innate immune system by acting as an immunomodulator and reducing inflammation in experimental and human IBD. The active form of vitamin D, 1,25(OH)D3, acts on T cells to promote T helper (Th)2/regulatory T responses over Th1/Th17 responses; suppresses dendritic cell inflammatory activity; induces antibacterial activity; and regulates cytokine production in favor of an anti-inflammatory response. Murine and human IBD studies support a therapeutic role of vitamin D in IBD. Risk factors for vitamin D deficiency in this population include decreased sunlight exposure, disease duration, smoking, and genetics. Vitamin D normalization is associated with reduced risk of relapse, reduced risk of IBD-related surgeries, and improvement in quality of life. Vitamin D is an inexpensive supplement which has been shown to improve IBD outcomes. However, further research is required to determine optimal serum vitamin D levels which will achieve beneficial immune effects, and stronger evidence is needed to support the role of vitamin D in inducing disease response and remission, as well as maintaining this improvement in patients’ disease states.

关键词： Vitamin D Inflammatory bowel disease Immune response Inflammation Cytokines Supplementation

Validation of the Rockall scoring system for outcomes from non-variceal upper gastrointestinal bleeding in a Canadian setting

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World Journal of Gastroenterology 2006年第48期12卷 7779-7785页

作者： Robert A Enns Yves M Gagnon Alan n Barkun David Armstrong Jamie C Gregor richard n Fedorak RUGBE Investigators Group Division of Gastroenterology University of British Columbia Vancouver Canada Occam Research & Consulting Inc. VancouverCanada Department of Medicine Division of Gastroenterology McGill University and the McGill UniversityHealth Center Montreal Canada Division of Gastroenterology McMaster University Medical Centre Hamilton Canada Division of Gastroenterology University of Western Ontario London Canada Division of Gastroenterology University of Alberta Edmonton Canada 不详

AIM: To validate the Rockall scoring system for predicting outcomes of rebleeding, and the need for a surgical procedure and death. METHODS: We used data extracted from the Registry of Upper Gastrointestinal Bleeding and Endoscopy including information of 1869 patients with non-variceal upper gastrointestinal bleeding treated in Canadian hospitals. Risk scores were calculated and used to classify patients based on outcomes. For each outcome, we used χ2 goodness-of-fit tests to assess the degree of calibration, and built receiver operating characteristic curves and calculated the area under the curve (AUC) to evaluate the discriminative ability of the scoring system. RESULTS: For rebleeding, the χ2 goodness-of-fit test indicated an acceptable fit for the model [χ2 (8) = 12.83, P = 0.12]. For surgical procedures [χ2 (8) = 5.3, P = 0.73] and death [χ2 (8) = 3.78, P = 0.88], the tests showed solid correspondence between observed proportions and predicted probabilities. The AUC was 0.59 (95% CI: 0.55-0.62) for the outcome of rebleeding and 0.60 (95% CI: 0.54-0.67) for surgical procedures, representing apoor discriminative ability of the scoring system. For the outcome of death, the AUC was 0.73 (95% CI: 0.69-0.78), indicating an acceptable discriminative ability. COnCLUSIOn: The Rockall scoring system provides an acceptable tool to predict death, but performs poorly for endpoints of rebleeding and surgical procedures.

关键词： Upper gastrointestinal bleeding nonvariceal Predictors Rockall Outcomes

Demographic trends and climate over 35 years in the Barro Colorado 50 ha plot

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Forest Ecosystems 2017年第4期4卷 273-285页

作者： richard Condit Rolando Pérez Suzanne Lao Salomón Aguilar Stephen P. Hubbell Field Museum of natural History 1400 S

Background： The first three censuses of the 50-ha plot at Barro Colorado Island spanned an unusually harsh dry season during the 1983 El nitro. By the early 1990s, we had documented increases in tree mortality, tree growth, and large population fluctuations of many species during the 1982-1985 census interval. At the time, we asserted that increasing drought frequency would greatly affect the forest. With the benefit of five more censuses at Barro Colorado from 1995-2015, we can now put the 1980 conditions in a longer perspective and test the hypothesis that increasing droughtiness has continued to change the forest. Methods： A 50-ha forest plot on Barro Colorado Island was censused eight times, in 1982 and every five years since 1985. All free-standing woody stems were measured, mapped, and identified in each census. Results： 1） The period 1982-1992 included several extreme dry seasons, not just 1983, but since then there have been few such droughts. 2） Dbh growth declined from a peak in the early 1980s to its lowest in the early 1990s. From 1995-2015 it increased slightly, but not returning to the initial peak. nearly every species and all dbh categories followed the same pattern. 3） The elevated stand-wide mortality rate of large trees during the 1982-1985 drought has not returned, and most individual species showed the same pattern of elevated mortality in the 1980s followed by low and fairly stable mortality after 1990. 4） Sapling mortality declined after 198,5, but rose again in the late-90s, so the 1980s drought period no longer looks unusual. Mortality of individual species＇ saplings fluctuated erratically, including cases where mortality during the drought was lower than after. 5） Population sizes of individual species fluctuated in all possible directions. Some species declined precipitously during the drought, then recovered, but others did not recover. Other species increased in abundance during the drought. Conclusions＂ Droughts of the 1980s elevated tr

关键词： Demographic trends climate