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      The Relationship between Ventricular Repolarization Duration and RR Interval in Normal Subjects and Patients with Myocardial Infarction

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          Abstract

          Objectives: When either ventricular myocardium becomes ischemic or autonomic nervous system activity changes with age, the relationship between ventricular repolarization duration and RR interval will change as well. We studied the relationship between ventricular repolarization duration and RR interval among normal subjects in different age groups and between patients with myocardial infarction (MI) and age-matched healthy subjects. Methods: Ventricular repolarization duration variability (RDV) spectra were separated into RR-dependent and RR-independent components. We compared spectral measures among normal subjects in different age groups and between patients with MI and age-matched healthy subjects. Results: The RR-dependent component of RDV spectra, which is correlated with autonomic nervous system activity, significantly decreased with age for healthy subjects. The RR-independent component significantly increased in MI patients compared to age-matched healthy subjects. Conclusions: We demonstrated the increase in RDV upon decreasing age and in the presence of MI. Our results support the idea that the RR-dependent part corresponds to the physiology-related part of the RDV spectra and the RR-independent part corresponds to the pathology-related part of the RDV spectra. Our study suggests that these spectral measures are likely to be helpful in the evaluation of a patient with MI and merit further investigation.

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          Most cited references 19

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          Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes

          Bacterial pathogens evolve during the infection of their human hosts 1-8 , but separating adaptive and neutral mutations remains challenging 9-11 . Here, we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple patients. We conducted a retrospective study of a Burkholderia dolosa outbreak among people with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired non-synonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes illuminate the genetic basis of important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition, and implicate oxygen-dependent gene regulation as paramount in lung infections. Several genes have not been previously implicated in pathogenesis, suggesting new therapeutic targets. The identification of parallel molecular evolution suggests key selection forces acting on pathogens within humans and can help predict and prepare for their future evolutionary course.
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            HIV-1 adaptation to NK cell mediated immune pressure

            Natural Killer (NK) cells play an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors 1–3 . Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory Killer Immunoglobulin-like receptors (KIRs) 4–7 . However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino acid polymorphisms in the HIV-1 sequence of chronically infected individuals on a population level. We show that these KIR-associated HIV-1 sequence polymorphisms can enhance the binding of inhibitory KIRs to HIV-1-infected CD4+ T cells, leading to reduced antiviral activity of KIR+ NK cells. These data demonstrate that KIR+ NK cells can place immunological pressure on HIV-1, and that the virus can evade such NK cell mediated immune pressure by selecting for sequence polymorphisms, as previously described for virus-specific T cells and neutralizing antibodies 8 . NK cells might therefore play a previously underappreciated role in contributing to viral evolution.
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              Antiviral Activity and Increased Host Defense against Influenza Infection Elicited by the Human Cathelicidin LL-37

              The extensive world-wide morbidity and mortality caused by influenza A viruses highlights the need for new insights into the host immune response and novel treatment approaches. Cationic Host Defense Peptides (CHDP, also known as antimicrobial peptides), which include cathelicidins and defensins, are key components of the innate immune system that are upregulated during infection and inflammation. Cathelicidins have immunomodulatory and anti-viral effects, but their impact on influenza virus infection has not been previously assessed. We therefore evaluated the effect of cathelicidin peptides on disease caused by influenza A virus in mice. The human cathelicidin, LL-37, and the murine cathelicidin, mCRAMP, demonstrated significant anti-viral activity in vivo, reducing disease severity and viral replication in infected mice to a similar extent as the well-characterized influenza virus-specific antiviral drug zanamivir. In vitro and in vivo experiments suggested that the peptides may act directly on the influenza virion rather than via receptor-based mechanisms. Influenza virus-infected mice treated with LL-37 had lower concentrations of pro-inflammatory cytokines in the lung than did infected animals that had not been treated with cathelicidin peptides. These data suggest that treatment of influenza-infected individuals with cathelicidin-derived therapeutics, or modulation of endogenous cathelicidin production may provide significant protection against disease.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2008
                September 2008
                25 April 2008
                : 111
                : 3
                : 209-218
                Affiliations
                aDepartment of Medicine and Center for Cardiovascular Research, bDepartment of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Ill., USA, and cShanghai Second Medical University, Shanghai, China
                Article
                121607 Cardiology 2008;111:209–218
                10.1159/000121607
                18434728
                © 2008 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 6, Tables: 1, References: 32, Pages: 10
                Categories
                Original Research

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