bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biventricular Defibrillator Patients Have Higher Complication Rates after Revision of Recalled Leads
Authors: BRUMBERG GENEVIEVE E. , KASEER BAHAA , SHAH HEMAL , SABA SAMIR , JAIN SANDEEP 
Published: April 2012

Background:

Since the 2009 revised advisory statement regarding Sprint Fidelis® Defibrillator Lead failure rates (Medtronic Inc., Minneapolis, MN, USA), there has been a significant increase in revision of these leads. We sought to establish the frequency of major procedural complications and determine what patient characteristics were associated with these outcomes.
Methods:

We retrospectively reviewed the charts of 621 patients with Fidelis® leads being followed in the University of Pittsburgh Medical Center through January 1, 2010. The population was then examined for rates of lead malfunction, revision, and complication.
Results:

The average time from implantation of Fidelis® lead to endpoint was 32 ± 16 months. Overall lead survival rates were 89% at 41 months and were lower in biventricular implantable cardioverter defibrillator (BiVICD) as compared to standard implantable cardioverter defibrillator patients (log rank P = 0.053). Prophylactic revisions increased dramatically during 2009 (9.4% vs 1.4%, P < 0.001). Among the 131 patients who underwent revision during the entire time of follow‐up, 11 patients had postoperative complications (8.5%). The only significant variable found between patients who did and did not have complications was the presence of a BiVICD (81.8 vs 48.7%, P = 0.036). Of the 40 total patients who underwent lead extraction, all three complications occurred in patients with BiVICDs.
Conclusion:

The number of prophylactic Fidelis® lead revisions has increased dramatically since 2008, and procedure‐related complications have been higher than anticipated. Major procedural complication rates are greater among patients with BiVICDs. Overall, lead extraction does not appear to increase procedural risk as compared to abandonment. (PACE 2012; 35:665–671)
Noise, Artifact, and Oversensing Related Inappropriate ICD Shock Evaluation: ALTITUDE NOISE Study
Authors: POWELL BRIAN D. , ASIRVATHAM SAMUEL J. , PERSCHBACHER DAVID L. , JONES PAUL W. , CHA YONG‐MEI , CESARIO DAVID A. , CAO MICHAEL , GILLIAM, III F. ROOSEVELT , SAXON LESLIE A. 
Published: April 2012

Background:

Approximately 12–21% of implantable cardioverter defibrillator (ICD) patients receive inappropriate shocks. We sought to determine the incidence and causes of noise/artifact and oversensing (NAO) resulting in ICD shocks.
Methods:

A random sample of 2,000 patients who received ICD and cardiac resynchronization therapy defibrillator shocks and were followed by a remote monitoring system was included. Seven electrophysiologists analyzed stored electrograms from the 5,279 shock episodes. Episodes were adjudicated as appropriate or inappropriate shocks.
Results:

Of the 5,248 shock episodes with complete adjudication, 1,570 (30%) were judged to be inappropriate shocks. Of these 1,570, 134 (8.5%) were a result of NAO. The 134 NAO episodes were determined to be due to external noise in 76 (57%), lead connector‐related in 37 (28%), muscle noise in 11 (8%), oversensing of atrium in seven (5%), T‐wave oversensing in two (2%), and other noise in one (1%). The ICD shock itself resulted in a marked decrease in the level of noise in 60 of 134 (45%) NAO episodes, and the magnitude of this effect varied with the type of NAO (58% for external noise, 35% for muscle, 27% for lead/connector, and 0% for oversensing; P = 0.03). There was no significant difference in NAO likelihood based on type of lead (integrated bipolar 89/1,802 vs dedicated bipolar 9/140, P = 0.67).
Conclusions:

External noise and lead/connector noise were the primary causes, while T‐wave oversensing was the least common cause of NAO resulting in ICD shock. Noise/artifact decreased immediately after a shock in nearly half of episodes. The specific ICD lead type did not impact the likelihood of NAO. (PACE 2012;XX:1–7)
Clinical Mapping Approach To Diagnose Electrical Rotors and Focal Impulse Sources for Human Atrial Fibrillation
Authors: NARAYAN SANJIV M. , KRUMMEN DAVID E. , RAPPEL WOUTER‐JAN 
Published: April 2012

Computational Mapping of Rotors and Focal Impulses in Human AF. Introduction: The perpetuating mechanisms for human atrial fibrillation (AF) remain undefined. Localized rotors and focal beat sources may sustain AF in elegant animal models, but there has been no direct evidence for localized sources in human AF using traditional methods. We developed a clinical computational mapping approach, guided by human atrial tissue physiology, to reveal sources of human AF.
Methods and Results:
In 49 AF patients referred for ablation (62 ± 9 years; 30 persistent), we defined repolarization dynamics using monophasic action potentials (MAPs) and recorded AF activation from 64‐pole basket catheters in left atrium and, in n = 20 patients, in both atria. Careful positioning of basket catheters was required for optimal mapping. AF electrograms at 64–128 electrodes were combined with repolarization and conduction dynamics to construct spatiotemporal AF maps. We observed sustained sources in 47/49 patients, in the form of electrical rotors (n = 57) and focal beats (n = 11) that controlled local atrial activation with peripheral wavebreak (fibrillatory conduction). Patients with persistent AF had more sources than those with paroxysmal AF (2.1 ± 1.0 vs 1.5 ± 0.8, P = 0.02), related to shorter cycle length (163 ± 19 milliseconds vs 187 ± 25 milliseconds, P < 0.001). Approximately one‐quarter of sources lay in the right atrium.
Conclusions:
Physiologically guided computational mapping revealed sustained electrical rotors and repetitive focal beats during human AF for the first time. These localized sources were present in 96% of AF patients, and controlled AF activity. These results provide novel mechanistic insights into human AF and lay the foundation for mechanistically tailored approaches to AF ablation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 447‐454, May 2012)
Endothelial Feedback and the Myoendothelial Projection
Authors: KERR PAUL M. , TAM RAYMOND , ONDRUSOVA KATARINA , MITTAL ROHAN , NARANG DEEPAK , TRAN CAM HA T. , WELSH DONALD G. , PLANE FRANCES 
Published: April 2012

Please cite this paper as: Kerr PM, Tam R, Ondrusova K, Mittal R, Narang D, Tran CHT, Welsh DG, Plane F. Endothelial feedback and the myoendothelial projection. Microcirculation 19: 416‐422, 2012.AbstractThe endothelium plays a critical role in controlling resistance artery diameter, and thus blood flow and blood pressure. Circulating chemical mediators and physical forces act directly on the endothelium to release diffusible relaxing factors, such as NO, and elicit hyperpolarization of the endothelial cell membrane potential, which spreads to the underlying smooth muscle cells via gap junctions (EDH). It has long been known that arterial vasoconstriction in response to agonists is limited by the endothelium, but the question of how contraction of smooth muscle cells leads to activation of the endothelium (myoendothelial feedback) has, until recently, received little attention. Initial studies proposed the permissive movement of Ca2+ ions from smooth muscle to endothelial cells to elicit release of NO. However, more recent evidence supports the notion that flux of IP3 leading to localized Ca2+ events within spatially restricted myoendothelial projections and activation of EDH may underlie myoendothelial feedback. In this perspective, we review recent data which supports the functional role of myoendothelial projections in smooth muscle to endothelial communication. We also discuss the functional evidence supporting the notion that EDH, as opposed to NO, is the primary mediator of myoendothelial feedback in resistance arteries.
Determinants for Arabidopsis Peptide Transporter Targeting to the Tonoplast or Plasma Membrane
Authors: Komarova Nataliya Y. , Meier Stefan , Meier Anna , Grotemeyer Marianne Suter , Rentsch Doris 
Published: April 2012

AbstractDi‐ and tripeptide transporters of the PTR/NRT1 (peptide transporter/nitrate transporter1)‐family are localized either at the tonoplast (TP) or plasma membrane (PM). As limited information is available on structural determinants required for targeting of plant membrane proteins, we performed gene shuffling and domain swapping experiments of Arabidopsis PTRs. A 7 amino acid fragment of the hydrophilic N‐terminal region of PTR2, PTR4 and PTR6 was required for TP localization and sufficient to redirect not only PM‐localized PTR1 or PTR5, but also sucrose transporter SUC2 to the TP. Alanine scanning mutagenesis identified L11 and I12 of PTR2 to be essential for TP targeting, while only one acidic amino acid at position 5, 6 or 7 was required, revealing a dileucine (LL or LI) motif with at least one upstream acidic residue. Similar dileucine motifs could be identified in other plant TP transporters, indicating a broader role of this targeting motif in plants. Targeting to the PM required the loop between transmembrane domain 6 and 7 of PTR1 or PTR5. Deletion of either PM or TP targeting signals resulted in retention in internal membranes, indicating that PTR trafficking to these destination membranes requires distinct signals and is in both cases not by default.
Review article: A primer for clinical researchers in the emergency department: Part III: How to write a scientific paper
Authors: Davidson Andrew , McD Taylor David , Babl Franz E 
Published: April 2012

AbstractIn this series we address key topics for clinicians who conduct research as part of their work in the ED. Analysis of research data does not represent the completion of a project as the findings need to be communicated to clinicians and other researchers in the field. In this section, we describe how to write up clinical research data for publication in a peer‐reviewed journal. We also describe the editorial and peer‐review process.
Sodium Consumption Among Hypertensive Adults Advised to Reduce Their Intake: National Health and Nutrition Examination Survey, 1999–2004
Authors: Ayala Carma , Gillespie Cathleen , Cogswell Molly , Keenan Nora L. , Merritt Robert 
Published: April 2012

J Clin Hypertens (Greenwich). 2012; 14:447–454. ©2012 Wiley Periodicals, Inc.The authors estimated the prevalence of taking action to reduce intake related to actual sodium consumption among 2970 nonpregnant US adults 18 years and older with self‐reported hypertension by using data from the National Health and Nutrition Examination Survey 1999–2004. Adjusted multiple linear regression assessed differences in mean sodium intake by action status. A total of 60.5% of hypertensive adults received advice to reduce sodium intake. Of this group, 83.7% took action to reduce sodium. Action to reduce sodium intake differed significantly by age, race/ethnicity, and use of an antihypertensive. The mean (±standard error) sodium intake among hypertensive adults was 3341±37 mg and differed by sex, age, race/ethnicity, education, and body mass index (P<.05), with the lowest intake among adults aged 65 years and older (2780±48 mg). Mean intake did not differ significantly by action status either overall or by subgroup except for one age category: among patients 65 years and older, mean intake was significantly lower among those who took action (2715±63 mg) than among those who did not (3401±206 mg; P=.0124). Regardless of action, mean intake was well above 1999–2004 recommendations for daily sodium intake and about twice as high as the current recommendation for hypertensive adults (1500 mg).
Does Response of RAS Blockade on Serum K+ Levels Influence Its Glycemic‐Mitigating Response When Combined With Hydrochlorothiazide?
Authors: Deedwania Prakash C. , Zappe Dion H. , Egan Brent M. , Purkayastha Das , Samuel Rita , Sowers James R. 
Published: April 2012

J Clin Hypertens (Greenwich). 2012; 14:415–421. ©2012 Wiley Periodicals, Inc.The authors previously reported that addition of valsartan ameliorated the negative metabolic effects of hydrochlorothiazide in obese hypertensive patients through an enhanced postprandial insulin response. In this secondary analysis, the authors tested whether this enhanced insulin response to valsartan/hydrochlorothiazide was influenced by serum potassium levels, which were reduced to a lesser extent, when compared with amlodipine/hydrochlorothiazide. Results showed that the early insulin response with valsartan plus hydrochlorothiazide occurred regardless of serum potassium levels. Heightened insulin response was, however, not significantly different when patients with normal potassium (>3.9 mEq/L) at baseline and low potassium (≤3.9 mEq/L) at the end of the study were compared with the amlodipine/hydrochlorothiazide group. Despite the influence of serum potassium on insulin secretory response to a glucose challenge, the addition of valsartan maintained normoglycemia in patients given hydrochlorothiazide. Thus, the metabolic response to hydrochlorothiazide was improved with addition of valsartan through an enhanced insulin response that was not greatly affected by changes in potassium levels.
INTRODUCTION OF A COMPETENCY BASED HAEMODIALYSIS EDUCATION PROGRAMME: 5 YEARS EXPERIENCE
Authors: Cowperthwaite Jan , Schutt‐Aine Ruth , Herranen Marjatta , Sorribes Mari Paz 
Published: April 2012

SUMMARYThe quality of care that patients receive is fundamentally related to the knowledge and skills of the staff providing the care. To ensure that all staff within our dialysis clinic network has the knowledge and competence to provide the care, support and education that patients require, a competency based education programme was developed. Roll‐out of the programme commenced in 129 clinics in our dialysis clinic network during 2006–2007. Activity with this programme has continued. It is now translated into 12 languages and fully implemented in 11 countries. At the end of December 2010, 3,099 staff had completed the Basic Dialysis Programme and 3,125 staff had completed the Orientation Programme component of the education programme. Results of quality activities have enabled further programme development and have shown that the investment in staff education has benefited our organisation, staff and patients.
Role of vitamin D metabolism in cutaneous tumour formation and progression
Authors: Nemazannikova Natalie , Antonas Kiriakos , Dass Crispin R 
Published: April 2012

Abstract

Objectives
Very limited information is available on the role of vitamin D in skin carcinogenesis. For most individuals, skin cancer can be readily managed with surgery; however, some patients may face life-threatening neoplasia. Sun exposure, specifically UV radiation, is a causative agent for development of skin cancer, though, somewhat ironically, sunlight through the production of vitamin D may have protective effect against some skin cancers. This review focuses on the development and progression of cutaneous carcinogenesis and the role of vitamin D in the prevention of the initiation and progression of lethal skin cancers.

Key findings
Vitamin D is involved in regulation of multiple signalling pathways that have implications in carcinogenesis. Skin cancer metastasis depends on the tumour microenvironment, where vitamin D metabolites play a key role in prevention of certain molecular events involved in tumour progression. The vitamin D receptor (VDR) is a well-known potent regulator of cellular growth and differentiation.

Summary
The VDR's possible involvement in cell death, tumour microenvironment and angiogenesis makes it a candidate agent for cancer regulation.
Arenavirus Nucleoprotein Targets Interferon Regulatory Factor-Activating Kinase IKKε
Authors: Pythoud Christelle , Rodrigo W. W. Shanaka I. , Pasqual Giulia , Rothenberger Sylvia , Martínez-Sobrido Luis , de la Torre Juan Carlos , Kunz Stefan 
Published: April 2012

ABSTRACT
Arenaviruses perturb innate antiviral defense by blocking induction of type I interferon (IFN) production. Accordingly, the arenavirus nucleoprotein (NP) was shown to block activation and nuclear translocation of interferon regulatory factor 3 (IRF3) in response to virus infection. Here, we sought to identify cellular factors involved in innate antiviral signaling targeted by arenavirus NP. Consistent with previous studies, infection with the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) prevented phosphorylation of IRF3 in response to infection with Sendai virus, a strong inducer of the retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling (MAVS) pathway of innate antiviral signaling. Using a combination of coimmunoprecipitation and confocal microscopy, we found that LCMV NP associates with the IκB kinase (IKK)-related kinase IKKε but that, rather unexpectedly, LCMV NP did not bind to the closely related TANK-binding kinase 1 (TBK-1). The NP-IKKε interaction was highly conserved among arenaviruses from different clades. In LCMV-infected cells, IKKε colocalized with NP but not with MAVS located on the outer membrane of mitochondria. LCMV NP bound the kinase domain (KD) of IKKε (IKBKE) and blocked its autocatalytic activity and its ability to phosphorylate IRF3, without undergoing phosphorylation. Together, our data identify IKKε as a novel target of arenavirus NP. Engagement of NP seems to sequester IKKε in an inactive complex. Considering the important functions of IKKε in innate antiviral immunity and other cellular processes, the NP-IKKε interaction likely plays a crucial role in arenavirus-host interaction.
Two Crucial Early Steps in RNA Synthesis by the Hepatitis C Virus Polymerase Involve a Dual Role of Residue 405
Authors: Scrima Nathalie , Caillet-Saguy Célia , Ventura Michel , Harrus Déborah , Astier-Gin Thérèse , Bressanelli Stéphane 
Published: April 2012

ABSTRACT

The hepatitis C virus (HCV) NS5B protein is an RNA-dependent RNA polymerase essential for replication of the viral RNA genome.
In vitro
and presumably
in vivo
, NS5B initiates RNA synthesis by a
de novo
mechanism and then processively copies the whole RNA template. Dissections of
de novo
RNA synthesis by genotype 1 NS5B proteins previously established that there are two successive crucial steps in
de novo
initiation. The first is dinucleotide formation, which requires a closed conformation, and the second is the transition to elongation, which requires an opening of NS5B. We also recently published a combined structural and functional analysis of genotype 2 HCV-NS5B proteins (of strains JFH1 and J6) that established residue 405 as a key element in
de novo
RNA synthesis (P. Simister et al., J. Virol. 83:11926–11939, 2009; M. Schmitt et al., J. Virol 85:2565–2581, 2011). We hypothesized that this residue stabilizes a particularly closed conformation conducive to dinucleotide formation. Here we report similar
in vitro
dissections of
de novo
synthesis for J6 and JFH1 NS5B proteins, as well as for mutants at position 405 of several genotype 1 and 2 strains. Our results show that an isoleucine at position 405 can promote both dinucleotide formation and the transition to elongation. New structural results highlight a molecular switch of position 405 with long-range effects, resolving the implied paradox of how the same residue can successively favor both the closed conformation of the dinucleotide formation step and the opening necessary to the transition step.
Multiple Antigenic Sites Are Involved in Blocking the Interaction of GII.4 Norovirus Capsid with ABH Histo-Blood Group Antigens
Authors: Parra Gabriel I. , Abente Eugenio J. , Sandoval-Jaime Carlos , Sosnovtsev Stanislav V. , Bok Karin , Green Kim Y. 
Published: April 2012

ABSTRACT
Noroviruses are major etiological agents of acute viral gastroenteritis. In 2002, a GII.4 variant (Farmington Hills cluster) spread so rapidly in the human population that it predominated worldwide and displaced previous GII.4 strains. We developed and characterized a panel of six monoclonal antibodies (MAbs) directed against the capsid protein of a Farmington Hills-like GII.4 norovirus strain that was associated with a large hospital outbreak in Maryland in 2004. The six MAbs reacted with high titers against homologous virus-like particles (VLPs) by enzyme-linked immunoassay but did not react with denatured capsid protein in immunoblots. The expression and self-assembly of newly developed genogroup I/II chimeric VLPs showed that five MAbs bound to the GII.4 protruding (P) domain of the capsid protein, while one recognized the GII.4 shell (S) domain. Cross-competition assays and mutational analyses showed evidence for at least three distinct antigenic sites in the P domain and one in the S domain. MAbs that mapped to the P domain but not the S domain were able to block the interaction of VLPs with ABH histo-blood group antigens (HBGA), suggesting that multiple antigenic sites of the P domain are involved in HBGA blocking. Further analysis showed that two MAbs mapped to regions of the capsid that had been associated with the emergence of new GII.4 variants. Taken together, our data map antibody and HBGA carbohydrate binding to proximal regions of the norovirus capsid, showing that evolutionary pressures on the norovirus capsid protein may affect both antigenic and carbohydrate recognition phenotypes.
The IE180 Protein of Pseudorabies Virus Suppresses Phosphorylation of Translation Initiation Factor eIF2α
Authors: Van Opdenbosch N. , Van den Broeke C. , De Regge N. , Tabarés E. , Favoreel H. W. 
Published: April 2012

ABSTRACT

We have previously shown that the porcine alphaherpesvirus pseudorabies virus (PRV) efficiently interferes with phosphorylation of the eukaryotic translation initiation factor eIF2α. Inhibition of phosphorylation of eIF2α has been reported earlier for the closely related alphaherpesvirus herpes simplex virus 1 (HSV-1) through its ICP34.5 and US11 proteins. PRV, however, does not encode an ICP34.5 or US11 orthologue. Assays using cycloheximide, UV-inactivated PRV, or phosphonoacetic acid (PAA) showed that
de novo
expression of one or more (immediate) early viral protein(s) is required for interference with eIF2α phosphorylation. In line with this, a time course assay showed that eIF2α phosphorylation was abolished within 2 h after PRV inoculation. PRV encodes only one immediate-early protein, IE180, the orthologue of HSV-1 ICP4. As reported earlier, a combinational treatment of cells with cycloheximide and actinomycin D allowed expression of IE180 without detectable expression of the US3 early protein in PRV-infected cells. This led to a substantial reduction in eIF2α phosphorylation levels, indicative for an involvement of IE180. In support of this, transfection of IE180 also potently reduced eIF2α phosphorylation. IE180-mediated interference with eIF2α phosphorylation was not cell type dependent, as it occurred both in rat neuronal 50B11 cells and in swine testicle cells. Inhibition of the cellular phosphatase PP1 impaired PRV-mediated interference with eIF2α phosphorylation, indicating that PP1 is involved in this process. In conclusion, the immediate-early IE180 protein of PRV has the previously uncharacterized ability to suppress phosphorylation levels of the eukaryotic translation initiation factor eIF2α.