An Experimental Study on the Mechanical and Biological Properties of Bio-Printed Alginate/Halloysite Nanotube/Methylcellulose/Russian Olive-Based Scaffolds

Purpose: Cartilage shows neither repairs nor regenerative properties after trauma or gradual wear and causes severe pain due to bones rubbing. Bioprinting of tissue-engineered artificial cartilage is one of the most fast-growing sciences in this area that can help millions of people against this disease. Methods: Bioprinting of proper bioscaffolds for cartilage repair was the main goal of this study. The bioprinting process was achieved by a novel composition consisting of alginate (AL), Halloysite nanotube (HNT), and methylcellulose (MC) prepared in bio-ink. Also, the effect of Russian olive (RO) in chondrocytes growth on bioscaffolds was also investigated in this work. Compressive, hardness and viscosity tests, Energy-Dispersive X-Ray Spectroscopy (EDX), Fourier-Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), water-soluble Tetrazolium (WST) assay, and also transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were carried out. Results: The results show that in constant concentrations of AL, MC, and RO (20 mg/ml AL, 20 mg/ml MC, and 10 mg/ml RO) when concentration of HNT increased from 10 mg/ml (T-7) to 20 mg/ml (T-8) compressive stiffness increased from 241±45 kPa to 500.66±19.50 kPa. Also, 20 mg/ml of AL in composition saved proper water content for chondrocyte growth and produced good viscosity properties for a higher printing resolution. Conclusion: RO increased chondrocytes living cell efficiency by 11% on bioprinted scaffolds in comparison with the control group without RO. Results obtained through in-vivo studies were similar to those of in-vitro studies. According to the results, T-7 bio-ink has good potential in bioprinting of scaffolds in cartilage repairs

Evaluation of Immunomodulatory Biomarkers in a Pressure Overload Model of Heart Failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90380/1/phco.27.4.504.pd

Epithelial Neutrophil-Activating Peptide (ENA-78), Acute Coronary Syndrome Prognosis, and Modulatory Effect of Statins

Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelial neutrophil-activating peptide (ENA-78), is associated with ACS prognosis. We also investigated whether statin use, a potent modulator of inflammation, modifies CXCL5's association with outcomes and characterized the in vitro effect of atorvastatin on endothelial ENA-78 production. Using a prospective cohort of ACS patients (n = 704) the association of the CXCL5 −156 G>C polymorphism (rs352046) with 3-year all-cause mortality was estimated with hazard ratios (HR). Models were stratified by genotype and race. To characterize the influence of statins on this association, a statin*genotype interaction was tested. To validate ENA-78 as a statin target in inflammation typical of ACS, endothelial cells (HUVECs) were treated with IL-1β and atorvastatin with subsequent quantification of CXCL5 expression and ENA-78 protein concentrations. C/C genotype was associated with a 2.7-fold increase in 3-year all-cause mortality compared to G/G+G/C (95%CI 1.19–5.87; p = 0.017). Statins significantly reduced mortality in G/G individuals only (58% relative risk reduction; p = 0.0009). In HUVECs, atorvastatin dose-dependently decreased IL-1β-stimulated ENA-78 concentrations (p<0.0001). Drug effects persisted over 48 hours (p<0.01). CXCL5 genotype is associated with outcomes after ACS with potential statin modification of this effect. Atorvastatin lowered endothelial ENA-78 production during inflammation typical of ACS. These findings implicate CXCL5/ENA-78 in ACS and the statin response

Enrichment Strategies in Pediatric Drug Development: An Analysis of Trials Submitted to the US Food and Drug Administration

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146322/1/cpt971_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146322/2/cpt971.pd

Feasibility of incorporating genomic knowledge into electronic medical records for pharmacogenomic clinical decision support

In pursuing personalized medicine, pharmacogenomic (PGx) knowledge may help guide prescribing drugs based on a person’s genotype. Here we evaluate the feasibility of incorporating PGx knowledge, combined with clinical data, to support clinical decision-making by: 1) analyzing clinically relevant knowledge contained in PGx knowledge resources; 2) evaluating the feasibility of a rule-based framework to support formal representation of clinically relevant knowledge contained in PGx knowledge resources; and, 3) evaluating the ability of an electronic medical record/electronic health record (EMR/EHR) to provide computable forms of clinical data needed for PGx clinical decision support. Findings suggest that the PharmGKB is a good source for PGx knowledge to supplement information contained in FDA approved drug labels. Furthermore, we found that with supporting knowledge (e.g. IF age <18 THEN patient is a child), sufficient clinical data exists in University of Washington’s EMR systems to support 50% of PGx knowledge contained in drug labels that could be expressed as rules

Adrenergic gene polymorphisms and cardiovascular risk in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation

<p>Abstract</p> <p>Background</p> <p>Adrenergic gene polymorphisms are associated with cardiovascular and metabolic phenotypes. We investigated the influence of adrenergic gene polymorphisms on cardiovascular risk in women with suspected myocardial ischemia.</p> <p>Methods</p> <p>We genotyped 628 women referred for coronary angiography for eight polymorphisms in the α_1A-, β₁-, β₂- and β₃-adrenergic receptors (<it>ADRA1A</it>, <it>ADRB1, ADRB2</it>, <it>ADRB3</it>, respectively), and their signaling proteins, G-protein β 3 subunit (<it>GNB3</it>) and G-protein α subunit (<it>GNAS</it>). We compared the incidence of death, myocardial infarction, stroke, or heart failure between genotype groups in all women and women without obstructive coronary stenoses.</p> <p>Results</p> <p>After a median of 5.8 years of follow-up, 115 women had an event. Patients with the <it>ADRB1 </it>Gly389 polymorphism were at higher risk for the composite outcome due to higher rates of myocardial infarction (adjusted hazard ratio [HR] 3.63, 95% confidence interval [95%CI] 1.17–11.28; Gly/Gly vs. Arg/Arg HR 4.14, 95%CI 0.88–19.6). The risk associated with <it>ADRB1 </it>Gly389 was limited to those without obstructive CAD (n = 400, P_interaction= 0.03), albeit marginally significant in this subset (HR 1.71, 95%CI 0.91–3.19). Additionally, women without obstructive CAD carrying the <it>ADRB3 </it>Arg64 variant were at higher risk for the composite endpoint (HR 2.10, 95%CI 1.05–4.24) due to subtle increases in risk for all of the individual endpoints. No genetic associations were present in women with obstructive CAD.</p> <p>Conclusion</p> <p>In this exploratory analysis, common coding polymorphisms in the β₁- and β₃-adrenergic receptors increased cardiovascular risk in women referred for diagnostic angiography, and could improve risk assessment, particularly for women without evidence of obstructive CAD.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00000554.</p

2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93740/1/ACR_21772_sm_SupplFig2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93740/2/ACR_21772_sm_SupplFig4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93740/3/21772_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93740/4/ACR_21772_sm_SupplFig1.pd

Sex-specific regulation of chemokine Cxcl5/6 controls neutrophil recruitment and tissue injury in acute inflammatory states

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Barts and The London Trustees Studentship (SM), Marie Curie fellowships (MB, JD), Arthritis Research UK career development fellowship (JW), William Harvey Research Foundation grant (JW/RSS), Kidney Research UK fellowship (NSAP), Barts and The London Vacation Scholarship (ISN), Wellcome Trust senior fellowship (DWG), and a Wellcome Trust career development fellowship (RSS). This work forms part of the research themes contributing to the translational research portfolio of Barts and The London Cardiovascular Biomedical Research Unit, which is supported and funded by National Institute for Health Researc