152 research outputs found

    Melatonin reduces TNF-a induced expression of MAdCAM-1 via inhibition of NF-kB.

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    BACKGROUND: Endothelial MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the oxidant-dependent induction and progress of inflammatory bowel disease (IBD). Melatonin, a relatively safe, potent antioxidant, has shown efficacy in several chronic injury models may limit MAdCAM-1 expression and therefore have a therapeutic use in IBD. METHODS: We examined how different doses of melatonin reduced endothelial MAdCAM-1 induced by TNF-a in an in vitro model of lymphatic endothelium. Endothelial monolayers were pretreated with melatonin prior to, and during an exposure, to TNF-a (1 ng/ml, 24 h), and MAdCAM-1 expression measured by immunoblotting. RESULTS: MAdCAM-1 was induced by TNF-a. Melatonin at concentrations over 100 ÎŒm (10(-4) M) significantly attenuated MAdCAM-1 expression and was maximal at 1 mM. CONCLUSIONS: Our data indicate that melatonin may exert therapeutic activity in IBD through its ability to inhibit NF-kB dependent induction of MAdCAM-1

    N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

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    IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models

    Bioinorganic Chemistry of Alzheimer’s Disease

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    The United States COVID-19 Forecast Hub dataset

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    Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

    Iron uptake and transport across physiological barriers

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    Total 3D AiroÂź Navigation for Minimally Invasive Transforaminal Lumbar Interbody Fusion

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    Introduction. A new generation of iCT scanner, Airo¼, has been introduced. The purpose of this study is to describe how Airo facilitates minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Method. We used the latest generation of portable iCT in all cases without the assistance of K-wires. We recorded the operation time, number of scans, and pedicle screw accuracy. Results. From January 2015 to December 2015, 33 consecutive patients consisting of 17 men and 16 women underwent single-level or two-level MIS-TLIF operations in our institution. The ages ranged from 23 years to 86 years (mean, 66.6 years). We treated all the cases in MIS fashion. In four cases, a tubular laminectomy at L1/2 was performed at the same time. The average operation time was 192.8 minutes and average time of placement per screw was 2.6 minutes. No additional fluoroscopy was used. Our screw accuracy rate was 98.6%. No complications were encountered. Conclusions. Airo iCT MIS-TLIF can be used for initial planning of the skin incision, precise screw, and cage placement, without the need for fluoroscopy. “Total navigation” (complete intraoperative 3D navigation without fluoroscopy) can be achieved by combining Airo navigation with navigated guide tubes for screw placement

    Time-Window Sequential Analysis: An Introduction for Pediatric Psychologists

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    Objective Pediatric psychologists are often interested in interactions among individuals (e.g., doctors and patients, parents and children). Most research examining the nature of these interactions has used correlational analyses. Sequential analysis provides greater detail on contingencies during interactions and the way that interactions play out over time. The purpose of this article is to offer a non-technical introduction to sequential analyses for pediatric psychologists. Methods A more recent derivation of the basic method, called time-window sequential analysis, is introduced and distinguished from other forms of sequential analysis. Results A step-by-step pediatric psychology example of time-window sequential analysis is provided and the integration of sequential analysis with traditional statistical methods is discussed. An example of physician–child interaction during anesthesia induction is used to illustrate the technique. Conclusion Sequential analysis is a technique that is useful to pediatric psychologists who are interested in contingencies among data collected over time
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