bluuebunny/crossref_metadata_2025 huggingface dataset:
The Main Determinant of Hypotension in Nitroglycerine Tilt‐Induced Vasovagal Syncope
Authors: NIGRO GERARDO , RUSSO VINCENZO , RAGO ANNA , IOVINO MASSIMO , ARENA GIULIA , GOLINO PAOLO , RUSSO MARIA GIOVANNA , CALABRÒ RAFFAELE
Published: April 2012

Background:

The aim of the study was to assess the main determinant of the fall in blood pressure (BP) responsible for the head‐up tilt testing‐induced syncope.

Methods and results:

The study involved 200 patients (mean age 42 ± 3; 81 male) with syncope of unknown origin after the first evaluation. According to the response to the diagnostic tilt test, the population study was divided into four groups: Group I with mixed vasovagal syncope; Group II with cardioinhibitory syncope; Group III with vasodepressive syncope; Group IV: 40 patients with clinical syncope but no tilt‐induced syncope. Finger arterial BP (Portapres, TNO, Amsterdam, the Netherlands) was recorded during tilt testing. Left ventricular stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were computed from the pressure pulsations (Modelflow, TNO, Amsterdam, the Netherlands). During syncopal phase, the TPR decreased significantly in Group III, and increased in Group I and in Group II. CO decreased in Group I and in Group II and did not change significantly in Group III. SV decreased significantly in all groups.

Conclusions:

Our data showed that the arterial system appears to be the main determinant of the BP fall in vasodepressive vasovagal syncope; while the impaired constrictive response of the venous system, leading to reduced venous return to the heart, appears to be the main determinant of BP fall in mixed and cardioinhibitory vasovagal syncope. (PACE 2012; 35:739–748)
Clinical Characteristics and Mutational Analysis of the RyR2 Gene in Seven Czech Families with Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: ANDRSOVA IRENA , VALASKOVA IVETA , KUBUS PETER , VIT PAVEL , GAILLYOVA RENATA , KADLECOVA JITKA , MANOUSKOVA LENKA , NOVOTNY TOMAS
Published: April 2012

Background:

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare hereditary arrhythmia. The onset of clinical symptoms usually occurs during childhood, and is typically related to exercise. The aim of our study was to describe the clinical characteristics of seven Czech families with CPVT and the results of mutational analysis of the RyR2 gene in these families.

Methods:

The subjects and their relatives were investigated at the participating departments. They underwent basic clinical investigation, and history was focused on possible CPVT symptoms, that is, syncopes during exercise. Bicycle ergometry was performed to obtain electrocardiogram recording during adrenergic stimulation. In all the investigated individuals, blood samples were taken for mutation analysis of the RyR2 gene.

Results:

To date, seven families have been investigated, comprising 11 adults and 13 children. In seven CPVT patients, the indication for examination was syncope during exercise. Diagnosis was confirmed by bicycle ergometry‐induced polymorphic ventricular tachycardia. In one relative, polymorphic ventricular tachycardia was also induced. All eight affected individuals were treated with β‐blockers and in two, a cardioverter‐defibrillator was implanted due to recurrent syncopi. Coding variants of the RyR2 gene were found in four probands.

Conclusions:

This is a systematic description of CPVT families in the Czech Republic. Our data support the importance of exercise testing for the diagnosis of CPVT. In addition, RyR2 gene coding variants were found in 50% of affected individuals. (PACE 2012;1–5)
Percutaneous Extraction of Cardiac Implantable Electronic Devices (CIEDs) in Octogenarians
Authors: WILLIAMS STEVEN E. , ARUJUNA ARUNA , WHITAKER JOHN , SOHAL MANAV , SHETTY ANOOP K. , ROY DEBASHIS , BOSTOCK JULIAN , COOKLIN MICHAEL , GILL JASWINDER , O’NEILL MARK , WRIGHT MATTHEW , PATEL NIKHIL , BUCKNALL CLIFF , HAMID SHOAIB , RINALDI C. ALDO
Published: April 2012

Background:

As the population receiving cardiac device therapy ages, the number of extraction procedures performed in octogenarians is increasing. This group has more comorbidities and may be at higher risk of such procedures.

Objectives:

Document the safety and success of percutaneous lead extraction in octogenarians.

Methods:

All extraction cases performed between January 2001 and April 2011 entered into a computer database were analyzed for patient characteristics and indications, extraction technique, procedural success, and complications. Success and complications were classified according to the Heart Rhythm Society consensus statement. Outcomes in octogenarians were compared to younger patients undergoing extraction during the same period.

Results:

Four hundred and six cases were performed: 72 procedures in octogenarians (mean age 84, range 80–95) and 334 in younger adults (mean age 62, range 20–79). Octogenarians had a greater number of comorbidities per case. Infection was the commonest indication for extraction in both groups. One hundred forty‐one leads were extracted in octogenarians and 657 in younger patients. Laser assistance was required in 51.4% of octogenarians versus 49.7% of younger patients. Procedural success was achieved in 71/72 (98.6%) octogenarians versus 329/334 (98.5%) younger patients. No procedural mortality occurred in either group. Overall, complications were more frequent in octogenarians with major and minor complications occurring in 2.8 and 8.3% of octogenarians versus 0.6 and 3.0% of younger patients (P = 0.014).

Conclusions:

Procedural success was equally high in octogenarians and younger patients. Percutaneous lead extraction can be performed effectively and safely in octogenarians and is associated with a higher complication rate but no increased mortality. (PACE 2012;00:1–9)
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)
“Heart Rate‐Dependent” Electrocardiographic Diagnosis of Left Ventricular Hypertrophy
Authors: MADIAS JOHN E.
Published: April 2012

A case is presented revealing the common phenomenon of heart rate‐dependent diagnosis of electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH), which consists of satisfaction of LVH criteria only at faster rates whereas ECGs with a slow heart rate do not satisfy such criteria. The mechanism of the phenomenon has been attributed to the tachycardia‐mediated underfilling of the left ventricle bringing the electrical “centroid” of the heart closer to the recording electrodes, which results in augmentation of the amplitude of QRS complexes, particularly in leads V2–V4. (PACE 2013; 36:e136–e137)
Coronary Sinus Lead Fragmentation and Migration
Authors: ARIAS MIGUEL A. , PACHÓN MARTA , PUCHOL ALBERTO , JIMÉNEZ‐LÓPEZ JESÚS , CASARES‐MEDRANO JULIO
Published: April 2012

We report the case of a patient with ischemic cardiomyopathy who several years before underwent cardiac resynchronization therapy. He was admitted for surgical revision of the system due to coronary sinus lead failure. Percutaneous extraction of the lead was performed but an unusual complication related to the damaged lead occurred with relatively positive outcomes. (PACE 2012; 35:e149)
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)
Interplay between Arrhythmias Originating in the Right Ventricular Outflow Tract and the Left Coronary Cusp
Authors: KÜHNE MICHAEL , KNECHT SVEN , SCHAER BEAT , OSSWALD STEFAN , STICHERLING CHRISTIAN
Published: April 2012

A 35‐year‐old man was referred for ablation of ventricular tachycardia with two different morphologies triggering each other. After elimination of the first arrhythmia in the right ventricular outflow tract, ablation of the second morphology was performed 8 mm below the left main stem after contrast injection into the left coronary cusp through the irrigated‐tip ablation catheter. (PACE 2012;35:e356–e357)
Long QT Syndrome and Dilated Cardiomyopathy with SCN5A p.R1193Q Polymorphism: Cardioverter‐Defibrillator Implantation at 27 Months
Authors: KWON HYE WON , LEE SANG YOON , KWON BO SANG , KIM GI BEOM , BAE EUN JUNG , KIM WOONG HAN , NOH CHUNG IL , CHO SUNG IM , PARK SUNG SUP
Published: April 2012

Cardiac sodium channel dysfunction associated with the SCN5A gene presents with mixed phenotypes, including long QT syndrome type 3, sinus node dysfunction, and dilated cardiomyopathy (DCM). We report a Korean case of an overlap syndrome of cardiac sodium channelopathy with SCN5A p.R1193Q polymorphism, treated by the placement of an intrapericardial implantable cardioverter‐defibrillator (ICD) at the age of 27 months. Although the patient received two appropriate life‐saving shocks for ventricular fibrillations, he eventually died of DCM progression. However, this case shows that intrapericardial ICD implantation is feasible in young children with a high risk for sudden cardiac death. (PACE 2012; 35:e243–e246)
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)
Intracranial Hemorrhage as a Complication of Dobutamine Stress Echocardiography: Case Report and Review of the Literature
Authors: Shah Sachin P. , Muqtada Chaudhry G.
Published: April 2012

Dobutamine stress echocardiography is a generally well‐tolerated study to evaluate patients with suspected coronary artery disease. Rare but life‐threatening complications of this study have been well described. Severe hypertensive responses are a known but uncommon adverse reaction to dobutamine infusion. The authors report a case of intracranial hemorrhage in the setting of severe hypertension as a complication of dobutamine stress echocardiography. The patient was on systemic anticoagulation with warfarin for a prosthetic mitral valve and had an international normalized ratio (INR) of 3.8 that was slightly over the therapeutic goal INR of 2.5–3.5. He had no predisposing intracranial lesions such as tumor, vascular malformation, or aneurysm. He suffered an intraparenchymal hemorrhage in three distinct areas of his brain. Intracranial hemorrhage related to dobutamine infusion has not been reported previously, but given the known risk of hypertension, life‐threatening sequelae including intracranial hemorrhage are possible. (Echocardiography 2012;29:E119‐E121)
A Partitioning Deletion/Substitution/Addition Algorithm for Creating Survival Risk Groups
Authors: Lostritto Karen , Strawderman Robert L. , Molinaro Annette M.
Published: April 2012

Summary Accurately assessing a patient’s risk of a given event is essential in making informed treatment decisions. One approach is to stratify patients into two or more distinct risk groups with respect to a specific outcome using both clinical and demographic variables. Outcomes may be categorical or continuous in nature; important examples in cancer studies might include level of toxicity or time to recurrence. Recursive partitioning methods are ideal for building such risk groups. Two such methods are Classification and Regression Trees (CART) and a more recent competitor known as the partitioning Deletion/Substitution/Addition (partDSA) algorithm, both of which also utilize loss functions (e.g., squared error for a continuous outcome) as the basis for building, selecting, and assessing predictors but differ in the manner by which regression trees are constructed. Recently, we have shown that partDSA often outperforms CART in so‐called “full data” settings (e.g., uncensored outcomes). However, when confronted with censored outcome data, the loss functions used by both procedures must be modified. There have been several attempts to adapt CART for right‐censored data. This article describes two such extensions for partDSA that make use of observed data loss functions constructed using inverse probability of censoring weights. Such loss functions are consistent estimates of their uncensored counterparts provided that the corresponding censoring model is correctly specified. The relative performance of these new methods is evaluated via simulation studies and illustrated through an analysis of clinical trial data on brain cancer patients. The implementation of partDSA for uncensored and right‐censored outcomes is publicly available in the R package, partDSA.
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.

The 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.
Analysis of Dopamine D2 Receptor (DRD2) Gene Polymorphisms in Cannabinoid Addicts*
Authors: Nacak Muradiye , Isir Aysun B. , Balci Sibel O. , Pehlivan Sacide , Benlier Necla , Aynacioglu Sukru
Published: April 2012

Abstract:  The gene encoding the dopamine D2 receptor (DRD2) has been suggested as a candidate gene for substance dependence. In this study, the possible association between Taq1A and Taq1B DRD2 polymorphisms and cannabinoid dependence was investigated. One hundred and twelve cannabinoid addicted and 130 healthy control subjects were included in this study. The Taq1A and Taq1B genotypes were determined in all subjects by polymerase chain reaction. For each polymorphism (A or B), the subjects were categorized into three groups according to their genotype, that is, the subjects with alleles A1/A1, A1/A2, A2/A2; B1/B1, B1/B2, and B2/B2. A significant association was found between Taq1A gene polymorphism and cannabinoid addicts compared to the control subjects. This finding suggests that polymorphism of the Taq1A, but not the Taq1B, may be associated with the susceptibility to cannabinoid dependence. Further clinical studies are required to be carried out for confirmation and evaluation of these findings.
The Impact of Negative Campaign Ads
Authors: MARKS ERIC , MANNING MARK , AJZEN ICEK
Published: April 2012

We compared negative and positive ads in the context of a fictitious election. Participants read a strong or weak message supporting one candidate (positive ad) or derogating the opposition candidate (negative ad). The strong positive message had a greater impact on attitudes toward the candidates than the weak positive message, but message strength had no significant effect for negative messages, suggesting that positive messages are centrally processed, and negative messages serve mainly as peripheral cues. Accordingly, a strong positive message was more effective than a weak positive message, but a weak positive message was less effective than a weak negative message. We conclude that negative political ads are advisable only when candidates cannot provide strong arguments to support their candidacy.
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

Di‐ 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

In 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

The 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.
Metabolic Syndrome and Nocturia
Authors: AOKI Yoshitaka , YOKOYAMA Osamu
Published: April 2012

Nocturia is one of the most common urological symptoms in men and women. Its prevalence is significantly related to age, but the causes of nocturia are multifactorial, such as diabetes, obesity, and other diseases and conditions. Recently, it has been reported that metabolic syndrome (MetS) is associated with lower urinary tract symptoms, including incomplete emptying, intermittency, and nocturia. We reviewed the relationship between MetS and its components and nocturia. The results from our epidemiological study indicate that nocturia can be a marker not only of MetS but also of the precursor of MetS.
Role of vitamin D metabolism in cutaneous tumour formation and progression
Authors: Nemazannikova Natalie , Antonas Kiriakos , Dass Crispin R
Published: April 2012

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.

The VDR's possible involvement in cell death, tumour microenvironment and angiogenesis makes it a candidate agent for cancer regulation.
Measurement of Laminar Burning Speeds and Determination of Onset of Auto-Ignition of Jet-A/Air and Jet Propellant-8/Air Mixtures in a Constant Volume Spherical Chamber
Authors: Moghaddas Ali , Bennett Casey , Eisazadeh-Far Kian , Metghalchi Hameed
Published: April 2012

The laminar burning speeds of Jet-A/air and three different samples of jet propellant (JP-8)/air mixtures have been measured and the onset of auto-ignition in JP-8/air premixed mixtures has been determined. The experiments were made in a constant volume spherical vessel, which can withstand high pressures up to 400 atm. Burning speed was calculated from dynamic pressure rise due to the combustion process in the vessel. A thermodynamic model based on the pressure rise was used to determine the burning speed. The burning speeds were measured in lean mixtures for pressures of 1–4.5 atm and temperatures of 493–700 K. The onset of auto-ignition of JP-8 fuels was evaluated by observing intense fluctuations of pressure data during the explosion of the unburned gas. It was revealed that Jet-A and JP-8 have very similar burning speeds; however, auto-ignition temperatures of various samples of JP-8 were slightly different from each other. Auto-ignition of these fuels was much more sensitive to temperature rather than pressure.
Changes to the International Regulatory Environment
Authors: McHugh Martin , McCaffery Fergal , Casey Valentine
Published: April 2012

Since 2010, two significant international regulations regarding medical device development have come into force, the amendment to the European Union (EU) Medical Device Directive (MDD) 2007/47/EC and the United States (US) Food and Drug Administration (FDA) final rule on Medical Device Data Systems (MDDS). Adherence to these regulations is mandatory to be able to market a medical device in the respective region. The ability to understand these regulations and apply them to a development project can be difficult. The MDDS final rule changes the safety classification of a number of devices from Class III-high risk to Class I-low risk. The aim of this regulation is to make the process of achieving regulatory approval for manufacturers easier. The MDD aims to provide guidance for the development of medical devices to be marketed for use within the EU. It also provides defined pathways which manufacturers can follow in order to achieve regulatory approval. However, changes made as part of an amendment to the directive have a direct impact on the development of medical devices. One of the most significant changes as part of this amendment is for software to be potentially considered as a medical device in its own right and potentially the only element in a medical device subject to regulatory conformance. These regulations have created confusion surrounding specific areas, such as the use of mobile device applications for healthcare purposes. This article describes the key points of these latest regulatory changes that medical device manufacturers need to be aware of.
Ocean Salinities Reveal Strong Global Water Cycle Intensification During 1950 to 2000
Authors: Durack Paul J. , Wijffels Susan E. , Matear Richard J.
Published: April 2012

Getting Wetter Faster

Theoretical projections, based on the relationship between temperature and the amount of water vapor the atmosphere can hold, suggest that global warming should intensify the strength of the atmospheric water cycle by about twice the rate as the thermodynamics and climate models predict.

Durack
et al.

(p. 455) examined 50 years of observations of sea surface salinities and conclude that the patterns of change in the salinity data are consistent with the theoretical projections, rather than with those of the models. Thus, the global water cycle should intensify by 16 to 24% for a future increase of a global average temperature of 2 to 3°C.
Endogenous Protein S-Nitrosylation in
E. coli
: Regulation by OxyR
Authors: Seth Divya , Hausladen Alfred , Wang Ya-Juan , Stamler Jonathan S.
Published: April 2012

Handling Nitrosative Stress

S-nitrosylation of proteins is a principal mechanism of cellular signaling in eukaryotes but has not been reported in microbes. The transcription factor OxyR serves to protect bacterial cells from reactive oxygen species produced by cell metabolism in the presence of oxygen.

Seth
et al.

(p. 470) found that when cells grew in the presence of nitrate, OxyR was modified by S-nitrosylation of the same cysteine residue that gets oxidized in cells grown aerobically. However, the nitrosylated OxyR activated a different set of genes—some of which appeared to protect the cell from excessive S-nitrosylation.
Reprogramming the Genetic Code
Authors: Chin Jason W.
Published: April 2012

Incorporating unnatural amino acids into proteins presents challenges in expanding the genetic code.
Select Inflammasome Assembly
Authors: Caffrey Daniel R. , Fitzgerald Katherine A.
Published: April 2012

Inflammasomes that respond to pathogenic bacteria assemble in response to a specific cytoplasmic protein in macrophages.
Spending Panels Back Boosts for NSF, NASA, NIST Programs
Authors: Mervis Jeffrey
Published: April 2012

The National Science Foundation and NASA got off to a strong start last week in the annual congressional budget race.
Sarkozy's Foe Would Soften Reforms, Overturn Stem Cell Law
Authors: Casassus Barbara
Published: April 2012

If Socialist François Hollande wins France's presidential election, he would soften the impact of some of President Nicolas Sarkozy's higher education and research reforms and would try to repeal France's ban on embryonic stem cell research.
After a Successful Decade, Global Fight Appears Stalled
Authors: Kupferschmidt Kai
Published: April 2012

A new report estimates that global measles deaths declined dramatically between 2000 and 2007, but since 2007, the numbers have essentially remained flat.
Experiments Probe Language's Origins and Development
Authors: Normile Dennis
Published: April 2012

In a new twist for an old field, language researchers are heading to the laboratory to test hypotheses.
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

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

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

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

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.
What makes champions? A review of the relative contribution of genes and training to sporting success
Authors: Tucker Ross , Collins Malcolm
Published: April 2012

Elite sporting performance results from the combination of innumerable factors, which interact with one another in a poorly understood but complex manner to mould a talented athlete into a champion. Within the field of sports science, elite performance is understood to be the result of both training and genetic factors. However, the extent to which champions are born or made is a question that remains one of considerable interest, since it has implications for talent identification and management, as well as for how sporting federations allocate scarce resources towards the optimisation of high-performance programmes. The present review describes the contributions made by deliberate practice and genetic factors to the attainment of a high level of sporting performance. The authors conclude that although deliberate training and other environmental factors are critical for elite performance, they cannot by themselves produce an elite athlete. Rather, individual performance thresholds are determined by our genetic make-up, and training can be defined as the process by which genetic potential is realised. Although the specific details are currently unknown, the current scientific literature clearly indicates that both nurture and nature are involved in determining elite athletic performance. In conclusion, elite sporting performance is the result of the interaction between genetic and training factors, with the result that both talent identification and management systems to facilitate optimal training are crucial to sporting success.
Biomechanical insights into the aetiology of infraspinatus syndrome
Authors: Reeser Jonathan C , Fleisig Glenn S , Cools Ann M J , Yount Darcie , Magnes Scott A
Published: April 2012

Objective

Infraspinatus syndrome (IS) results from injury to the suprascapular nerve. For reasons that are poorly understood, volleyball players are at greater risk of developing IS than are athletes who compete in other overhead sports. Differences between the shoulder kinematics of volleyball-related overhead skills and those skills demanded by other overhead sports might explain the pronounced prevalence of IS among volleyball athletes.

Design

Observational, laboratory-based, cross-sectional study.

Setting

The American Sports Medicine Institute.

Participants

Fourteen healthy female Division 1 collegiate volleyball athletes.

Methods

Upper limb biomechanics of 14 healthy female Division 1 collegiate volleyball athletes while spiking and serving were quantified, then compared to the results from data previously obtained from female baseball pitchers and tennis players.

Results

Although the general movement pattern at the shoulder girdle is qualitatively similar for the upper limb skills required by a variety of overhead sports, volleyball spiking and serving result in greater shoulder abduction and horizontal adduction at the moment of ball contact/release than do baseball pitching or tennis serving.

Conclusion

The authors suggest that the unique scapular mechanics which permit the extreme shoulder abduction and horizontal adduction that characterise volleyball spiking and serving place anatomically predisposed volleyball athletes at increased risk for developing cumulative traction-related injury to the suprascapular nerve at the level of the spinoglenoid notch.