bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing intergovernmental contracts: The Canada–Manitoba cooperation on regional economic development
Authors: Conteh Charles
Published: June 2012

This article uses organization theory to examine the strengths and challenges of contractual arrangements between the federal government's Western Economic Diversification Canada (WD) and the Manitoba government to jointly manage regional economic development policy over the past two decades. This experience illustrates how strategies for managing intergovernmental cooperation on policy delivery are increasingly dictated by complex environmental forces, and how the survival of these contractual arrangements seems to rest on adaptive capacity in the face of constant change.
Decreased expression of neuronal nitric oxide synthase in the nucleus tractus solitarii inhibits sympathetically mediated baroreflex responses in rat
Authors: Lin Li‐Hsien , Nitschke Dragon Deidre , Jin Jingwen , Tian Xin , Chu Yi , Sigmund Curt , Talman William T.
Published: June 2012

Key points

Arteries send nerve signals to the brain in response to changes in blood pressure.

Nerves carrying these signals release chemical transmitters onto other neurons in the nucleus tractus solitarii, a nucleus in the brainstem.

One chemical that has been considered such a transmitter is nitric oxide, but there has been debate over the action of nitric oxide in brainstem influences on responses to changes blood pressure.

We show that use of a molecular tool that allows us to prevent the normal production of nitric oxide by nerve cells leads to altered reflex regulation of heart rate in rats.

Our findings, which clarify the role of neuronally derived nitric oxide in control of the cardiovascular system by the brain, could lead to better control of blood pressure in individuals with either high or low blood pressure.

Abstract  Despite numerous studies it remains controversial whether nitric oxide (NO·) synthesized by neuronal NOS (nNOS) plays an excitatory or inhibitory role in transmission of baroreflex signals in the nucleus tractus solitarii (NTS). In the current studies we sought to test the hypothesis that nNOS is involved in excitation of baroreflex pathways in NTS while excluding pharmacological interventions in assessing the influence of nNOS. We therefore developed, validated and utilized a short hairpin RNA (shRNA) to reduce expression of nNOS in the NTS of rats whose baroreflex activity was then studied. We demonstrate downregulation of nNOS through transduction with adeno‐associated virus type 2 (AAV2) carrying shRNA for nNOS. When injected bilaterally into NTS AAV2nNOSshRNA significantly reduced reflex tachycardic responses to acute hypotension while not affecting reflex bradycardic responses to acute increases of arterial pressure. Control animals treated with intravenous propranolol to block sympathetically mediated chronotropic responses manifested the same baroreflex responses as animals that had been treated with AAV2nNOSshRNA. Neither AAV2 eGFP nor AAV2nNOScDNA affected baroreflex responses. Blocking cardiac vagal influences with atropine similarly reduced baroreflex‐mediated bradycardic responses to increases in arterial pressure both in control animals and in those treated with AAV2nNOSshRNA. We conclude that NO· synthesized by nNOS in the NTS is integral to excitation of baroreflex pathways involved in reflex tachycardia, a largely sympathetically mediated response, but not reflex bradycardia, a largely parasympathetically mediated response. We suggest that, at the basal state, nNOS is maximally engaged. Thus, its upregulation does not augment the baroreflex.
Adhesive Elastic Contact of Rough Surfaces with Power-Law Axisymmetric Asperities
Authors: Wang Lefeng , Rong Weibin , Shao Bing , Sun Lining
Published: June 2012

The contact model for rough surfaces with power-law axisymmetric asperities in the presence of adhesion is developed. The extended JKR adhesive contact model for power-law axisymmetric asperities, denoted as JKR-n, developed by Zheng and Yu (2007,“Using the Dugdale Approximation to Match a Specific Interaction in the Adhesive Contact of Elastic Objects,” J. Colloid Interface Sci., 310, pp. 27–34) is utilized to investigate the adhesive contact of rough surfaces. The JKR-n adhesive contact model generalizes the most adopted JKR model for spherical objects of n = 2. This work compares the effect of surface roughness on the adhesion force for rough surfaces with various power-law axisymmetric asperities. It is found that shapes of the asperities influence the pull-off forces greatly during the separation of rough surfaces. A general adhesion parameter that includes the shape index of asperities is proposed, and it can be used to characterize the adhesion performance of rough surfaces.
Measured and Predicted Static Friction for Real Rough Surfaces in Point Contact
Authors: García Jose M. , Martini Ashlie
Published: June 2012

A numerical model to predict static friction for metallic point contacts was developed and validated by comparison to experimental measurements using a specially designed test rig. Key aspects of the numerical model were the incorporation of a digitized real rough surface profile, application of discrete convolution fast Fourier transform (DC-FFT) to predict local asperity interference, and modification of the yield strength to capture the effect of cold hardening. It was found that these model features are critically important to quantitative prediction of static friction. The model significantly underestimated the static friction coefficient if randomly generated surfaces having statistical parameters the same as the measured rough surface were used; digitized real rough surfaces enabled accurate predictions. Further, the model was able to describe the static friction of worn surfaces after cold hardening was introduced through modification of material yield strength. This work illustrates the importance of incorporating the surface features and the change of those features with wear to accurately and reliably predict static friction.
Science Signaling
Podcast: 12 June 2012
Authors: Ferguson Shawn M. , VanHook Annalisa M.
Published: June 2012

Regulated nuclear translocation of a transcription factor maintains lysosomal homeostasis.
Protecting Against a Barrier Breach
Authors: Mueller Kristen L.
Published: June 2012

Lymphocytes prevent bacteria from spreading beyond gut-associated lymphoid tissues and causing systemic inflammation.
Evading a Block on Translation
Authors: Foley John F.
Published: June 2012

A complex containing HIF-2α enables the translation of select mRNAs under hypoxic conditions when most protein synthesis is normally inhibited.
Rapid Redistribution of Phosphatidylinositol-(4,5)-Bisphosphate and Septins during the Candida albicans Response to Caspofungin
Authors: Badrane Hassan , Nguyen M. Hong , Blankenship Jill R. , Cheng Shaoji , Hao Binghua , Mitchell Aaron P. , Clancy Cornelius J.
Published: June 2012

We previously showed that phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and septin regulation play major roles in maintaining
Candida albicans
cell wall integrity in response to caspofungin and other stressors. Here, we establish a link between PI(4,5)P2 signaling and septin localization and demonstrate that rapid redistribution of PI(4,5)P2 and septins is part of the natural response of
C. albicans
to caspofungin. First, we studied caspofungin-hypersusceptible
C. albicans irs4
and
inp51
mutants, which have elevated PI(4,5)P2 levels due to loss of PI(4,5)P2-specific 5′-phosphatase activity. PI(4,5)P2 accumulated in discrete patches, rather than uniformly, along surfaces of mutants in yeast and filamentous morphologies, as visualized with a green fluorescent protein (GFP)-pleckstrin homology domain. The patches also contained chitin (calcofluor white staining) and cell wall protein Rbt5 (Rbt5-GFP). By transmission electron microscopy, patches corresponded to plasma membrane invaginations that incorporated cell wall material. Fluorescently tagged septins Cdc10 and Sep7 colocalized to these sites, consistent with well-described PI(4,5)P2-septin physical interactions. Based on expression patterns of cell wall damage response genes,
irs4
and
inp51
mutants were firmly positioned within a group of caspofungin-hypersusceptible, septin-regulatory protein kinase mutants.
irs4
and
inp51
were linked most closely to the
gin4
mutant by expression profiling, PI(4,5)P2-septin-chitin redistribution and other phenotypes. Finally, sublethal 5-min exposure of wild-type
C. albicans
to caspofungin resulted in redistribution of PI(4,5)P2 and septins in a manner similar to those of
irs4
,
inp51
, and
gin4
mutants. Taken together, our data suggest that the
C. albicans
Irs4-Inp51 5′-phosphatase complex and Gin4 function upstream of PI(4,5)P2 and septins in a pathway that helps govern responses to caspofungin.
Comparative Efficacies of Human Simulated Exposures of Tedizolid and Linezolid against Staphylococcus aureus in the Murine Thigh Infection Model
Authors: Keel R. A. , Tessier P. R. , Crandon J. L. , Nicolau D. P.
Published: June 2012

Tedizolid (formally torezolid) is an expanded-spectrum oxazolidinone with enhanced
in vitro
potency against Gram-positive pathogens, including methicillin-susceptible
Staphylococcus aureus
(MSSA) and methicillin-resistant
S. aureus
(MRSA). The efficacies of human simulated exposures of tedizolid and linezolid against
S. aureus
in an immunocompetent mouse thigh model over 3 days were compared. Four strains of MRSA and one of MSSA with tedizolid and linezolid MICs ranging from 0.25 to 0.5 and from 2 to 4 μg/ml, respectively, were utilized. Tedizolid or linezolid was administered in a regimen simulating a human steady-state 24-h area under the free concentration-time curve of 200 mg every 24 h (Q24) or 600 mg Q12, respectively. Thighs were harvested after 4, 8, 12, 24, 36, 48, and 72 h, and efficacy was determined by the change in bacterial density. The mean bacterial density in control mice increased over the 3-day period. After 24 h of treatment, a reduction in bacterial density of ≥1 log CFU was observed for both the tedizolid and linezolid treatments. Antibacterial activity was enhanced for both agents with a reduction of ≥2.6 log CFU after 72 h of treatment. Any statistically significant differences (
P
≤ 0.05) in efficacy between the agents were transient and did not persist throughout the 72-h treatment period. The tedizolid and linezolid regimens demonstrated similar
in vivo
efficacies against the
S. aureus
isolates tested. Both agents were bacteriostatic at 24 h and bactericidal on the third day of treatment. These data support the clinical utility of tedizolid for skin and skin structure infections caused by
S. aureus
, as well as the bactericidal activity of the oxazolidinones after 3 days of treatment.
Impact of Penicillin Nonsusceptibility on Clinical Outcomes of Patients with Nonmeningeal Streptococcus pneumoniae Bacteremia in the Era of the 2008 Clinical and Laboratory Standards Institute Penicillin Breakpoints
Authors: Choi Seong-Ho , Chung Jin-Won , Sung Heungsup , Kim Mi-Na , Kim Sung-Han , Lee Sang-Oh , Kim Yang Soo , Woo Jun Hee , Choi Sang-Ho
Published: June 2012

To investigate the impact of penicillin nonsusceptibility on clinical outcomes of patients with nonmeningeal
Streptococcus pneumoniae
bacteremia (SPB), a retrospective cohort study was performed. The characteristics of 39 patients with penicillin-nonsusceptible SPB (PNSPB) were compared to those of a group of age- and sex-matched patients (
n
= 78) with penicillin-susceptible SPB (PSSPB). Susceptibility to penicillin was redetermined by using the revised Clinical and Laboratory Standards Institute (CLSI) penicillin breakpoints in CLSI document M100-S18. Although the PNSPB group tended to have more serious initial manifestations than the PSSPB group, the two groups did not differ significantly in terms of their 30-day mortality rates (30.8% versus 23.1%;
P
= 0.37) or the duration of hospital stay (median number of days, 14 versus 12;
P
= 0.89). Broad-spectrum antimicrobial agents, such as extended-spectrum cephalosporins, vancomycin, and carbapenem, were frequently used in both the PNSPB and PSSPB groups. Multivariate analysis revealed that ceftriaxone nonsusceptibility (adjusted odds ratio [aOR] = 4.88; 95% confidence interval [CI] = 1.07 to 22.27;
P
= 0.041) was one of the independent risk factors for 30-day mortality. Thus, when the 2008 CLSI penicillin breakpoints are applied and the current clinical practice of using wide-spectrum empirical antimicrobial agents is pursued, fatal outcomes in patients with nonmeningeal SPB that can be attributed to penicillin nonsusceptibility are likely to be rare. Further studies that examine the clinical impact of ceftriaxone nonsusceptibility in nonmningeal SPB may be warranted.
Increase of β-Lactam-Resistant Invasive Haemophilus influenzae in Sweden, 1997 to 2010
Authors: Resman Fredrik , Ristovski Mikael , Forsgren Arne , Kaijser Bertil , Kronvall Göran , Medstrand Patrik , Melander Eva , Odenholt Inga , Riesbeck Kristian
Published: June 2012

The proportions of
Haemophilus influenzae
resistant to ampicillin and other β-lactam antibiotics have been low in Sweden compared to other countries in the Western world. However, a near-doubled proportion of nasopharyngeal Swedish
H. influenzae
isolates with resistance to β-lactams has been observed in the last decade. In the present study, the epidemiology and mechanisms of antimicrobial resistance of
H. influenzae
isolates from blood and cerebrospinal fluid in southern Sweden from 1997 to 2010 (
n
= 465) were studied. Antimicrobial susceptibility testing was performed using disk diffusion, and isolates with resistance to any tested β-lactam were further analyzed in detail. We identified a significantly increased (
P
= 0.03) proportion of β-lactam-resistant invasive
H. influenzae
during the study period, which was mainly attributed to a significant recent increase of β-lactamase-negative β-lactam-resistant isolates (
P
= 0.04). Furthermore, invasive β-lactamase-negative β-lactam-resistant
H. influenzae
isolates from 2007 and onwards were found in higher proportions than the corresponding proportions of nasopharyngeal isolates in a national survey. Multiple-locus sequence typing (MLST) of this group of isolates did not completely separate isolates with different resistance phenotypes. However, one cluster of β-lactamase-negative ampicillin-resistant (BLNAR) isolates was identified, and it included isolates from all geographical areas. A truncated variant of a β-lactamase gene with a promoter deletion,
bla
TEM-1
-PΔ dominated among the β-lactamase-positive
H. influenzae
isolates. Our results show that the proportions of β-lactam-resistant invasive
H. influenzae
have increased in Sweden in the last decade.
Efavirenz Pharmacokinetics in Cerebrospinal Fluid and Plasma over a 24-Hour Dosing Interval
Authors: Yilmaz Aylin , Watson Victoria , Dickinson Laura , Back David
Published: June 2012

We determined the pharmacokinetics of efavirenz in plasma and cerebrospinal fluid (CSF) over a 24-h dosing interval in a patient who had undergone a lumbar drain because of cryptococcal meningitis. Drug concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry in paired CSF (n= 24) and plasma (n= 25) samples. The median plasma efavirenz concentration was 3,718 ng/ml (range, 2,439 to 4,952), and the median CSF concentration was 16.3 ng/ml (range, 7.3 to 22.3). The CSF/plasma area-under-the-curve ratio was 0.0044 corresponding to a CSF penetration of 0.44% of plasma.
Memantine and cholinesterase inhibitor combination therapy for Alzheimer's disease: a systematic review
Authors: Farrimond Lucy E , Roberts Emmert , McShane Rupert
Published: June 2012

Background

Memantine is licensed for moderate-to-severe Alzheimer's disease (AD). National Institute for Clinical Excellence (NICE) guidance does not recommend the use of memantine in combination with cholinesterase inhibitors (acetylcholinesterase inhibitor (AChEI)). The underpinning meta-analysis was disputed by the manufacturer.

Objectives

To compare the efficacy of AChEI monotherapy with combination memantine and AChEI therapy in patients with moderate-to-severe AD and to examine the impact of including unpublished data on the results.

Design

Systematic review and meta-analysis of randomised controlled trials.

Data sources

The Cochrane Dementia Group trial register, ALOIS, searched for the last time on 3 May 2011.

Data synthesis

Data from four domains (clinical global, cognition, function, behaviour and mood) were pooled. Sensitivity analyses examined the impact on the NICE-commissioned meta-analysis of restricting data to patients with moderate-to-severe AD and of including an unpublished trial of an extended release preparation of memantine.

Results

Pooled data from the trials, which were included in the NICE-commissioned meta-analysis but which were restricted to moderate-to-severe AD only, showed a small effect of combination therapy on cognition (standardised mean difference (SMD)=−0.29, 95% CI −0.45 to −0.14). Adding data from an unpublished trial of an extended release memantine (total three trials, 1317 participants) showed a small benefit of combination therapy on global scores (SMD=−0.20, 95% CI −0.31 to −0.09), cognition (SMD=−0.25, 95% CI −0.36 to −0.14) and behaviour and mood (SMD=−0.17, 95% CI −0.32 to −0.03) but not on function (SMD=−0.04, 95% CI −0.21 to 0.13) at 6 months. No clinical data have been reported from a 1-year trial, although this found ‘no significant benefit’ on any clinical measures at 1 year.

Conclusions

These results suggest that there may be a small benefit at 6 months of adding memantine to AChEIs. However, the impact on clinical global impression depends on exactly which studies are included, and there is no benefit on function, so its clinical relevance is not robustly demonstrated. Currently available information from randomised controlled trails indicates no benefit of combination therapy over monotherapy at 1 year. Legislation on the form and content of registry posted results is needed in Europe.
Association mapping of height and maturity across five environments using the sorghum mini core collection
Authors: Upadhyaya Hari D. , Wang Yi-Hong , Sharma Shivali , Singh Sube
Published: June 2012

Sorghum is a potential energy crop thanks to its high biomass productivity and low input. Biomass yield in sorghum is defined by height and maturity. To develop molecular breeding tools for genetic improvement of these two traits, we have identified simple sequence repeat markers linked to height and maturity using a pool-based association mapping technique. The sorghum mini core collection was evaluated across five environments for height and maturity. Seven tall and seven short accessions were selected based on their height in all environments. Likewise, six early- and 10 late-maturing accessions were selected mostly based on their maturity in two post-rainy seasons. Two additional height pools were constructed based on phenotypes in one environment. The three pairs of pools were screened with 703 SSR markers and 39 polymorphic markers were confirmed by individual genotyping. Association mapping of the 39 markers with 242 accessions from the mini core collection identified five markers associated with maturity or height. All were clustered on chromosomes 6, 9, and 10 with previously mapped height and maturity markers or QTLs. One marker associated with both height and maturity was 84 kb from recently cloned Ma1. These markers will lay a foundation for identifying additional height and maturity genes in sorghum.
Book Review: 'The Mobile Academy' by Clark Quinn
Authors: Rocco Stevie
Published: June 2012

eLearn magazine contributor Stevie Rocco explores Dr. Clark Quinn's "The Mobile Academy," which provides a comprehensive, strategic overview of mobile within the context of higher education.
My 10 Favorite Articles From 2011
Authors: Hart Jane
Published: June 2012

In Jane Hart's monthly column for eLearn she shares some "gems"—useful or valuable tools, resources, and products she has unearthed for learning and performance improvement/support. In this month's column she lists her 10 favorite articles from 2011.
The Four Tech Tools You Should Be Using in Your Classroom But Aren't
Authors: Leising Brown Bridget
Published: June 2012

This article details four online tools that classroom teachers can utilize to generate new instructional ideas and streamline organization: Prezi, Dropbox, Pinterest, and Springpad.
The Scourge of Abstract Abstracts
Authors: Tracey Ryan
Published: June 2012

In his latest "My Turn" column, Ryan Tracey takes issue with article abstracts. All too often, abstracts are an afterthought. A well-written abstract can make all the difference; if an article gets overlooked, the abstract may be the culprit. Tracey shares some tips how on to make your abstract more substantive.
A Practitioner's Dilemma: How can I calculate the value of communities of practice?
Authors: Storberg-Walker Julia
Published: June 2012

The purpose of this article is to describe a process for evaluating the return on investment (ROI) of communities of practice. Adapting Kirkpatrick's four-step model, Wenger, Trayner and deLaat produced a revolutionary new method for connecting specific CoP activities to organizational results. This article describes the method in order to help practitioners "prove" the value of CoPs to executive-level decision makers.
How to Build and Lead Successful Online Communities: Behaving appropriately
Authors: Laycock Nic
Published: June 2012

In this final part of his series on learning communities, eLearn contributor Nic Laycock discusses how to avoid bad behavior and foster a real sense of community.
An FPGA-Based Omnidirectional Vision Sensor for Motion Detection on Mobile Robots
Authors: Mori Jones Y. , Arias-Garcia Janier , Sánchez-Ferreira Camilo , Muñoz Daniel M. , Llanos Carlos H. , Motta J. M. S. T.
Published: June 2012

This work presents the development of an integrated hardware/software sensor system for moving object detection and distance calculation, based on background subtraction algorithm. The sensor comprises a catadioptric system composed by a camera and a convex mirror that reflects the environment to the camera from all directions, obtaining a panoramic view. The sensor is used as an omnidirectional vision system, allowing for localization and navigation tasks of mobile robots. Several image processing operations such as filtering, segmentation and morphology have been included in the processing architecture. For achieving distance measurement, an algorithm to determine the center of mass of a detected object was implemented. The overall architecture has been mapped onto a commercial low-cost FPGA device, using a hardware/software co-design approach, which comprises a Nios II embedded microprocessor and specific image processing blocks, which have been implemented in hardware. The background subtraction algorithm was also used to calibrate the system, allowing for accurate results. Synthesis results show that the system can achieve a throughput of 26.6 processed frames per second and the performance analysis pointed out that the overall architecture achieves a speedup factor of 13.78 in comparison with a PC-based solution running on the real-time operating system xPC Target.
Spatial Divisions and Fertility in India
Authors: Pillai Vijayan , Salehin Mashooq
Published: June 2012

The Indian subcontinent can be divided into four geographical divisions. In this paper, we characterize three of the four divisions; the Northern Plains, the Deccan Plateau, and the Northern Mountains or the Himalayan as regions with dissimilar climatic and physical resources. It is argued that human adaptations to these variations would be varied by differences in social organization of production and consumption resulting in differences in fertility differences across the three divisions. We found significant differences in the median age at motherhood as well as in the total family size. The effects of the three selected fertility determinants, age at marriage, years of woman's education, and level of child loss on family size also varied significantly across the three divisions. There is considerable homogeneity with respect to fertility levels within the zones considered in this study.
Enhancement of Efficiency and Lifetime of Blue Organic Light-Emitting Diodes Using Two Dopants in Single Emitting Layer
Authors: Yu Jianning , Wei Na , Li Chong , Wei Bin , Huang Wei , Tsuboi Taiju , Zhang Jianhua , Zhang Zhilin
Published: June 2012

We have demonstrated efficient blue organic light-emitting diode with the structure of indium tin oxide/4,4′,4″-tris(N-(2-naphthyl)-N-phenyl-amino)triphenylamine/1,4-bis[N-(1-naphthyl)-N′-phenylamino]-4,4′-diamine/9,10-di(2-naphthyl)anthracene (ADN): 1-4-di-[4-(N,N-di-phenyl)amino]styryl-benzene (DSA-ph) 3 wt%/tris-(8-hydroxyquinoline)aluminum/LiF/Al. Improved efficiencies and longer operational lifetime were obtained by codoping a styrylamine-based dopant BD-3 (0.1 wt%) into the emitting layer of ADN doped with DSA-ph compared to the case of non-codoping. This was due to the improved charge balance and expansion of exciton recombination zone. The better charge balance was obtained by reducing the electron mobility of ADN which was higher than the hole mobility in the case of non-codoping.
Hydrogen Peroxide in Inflammation: Messenger, Guide, and Assassin
Authors: Wittmann C. , Chockley P. , Singh S. K. , Pase L. , Lieschke G. J. , Grabher C.
Published: June 2012

Starting as a model for developmental genetics, embryology, and organogenesis, the zebrafish has become increasingly popular as a model organism for numerous areas of biology and biomedicine over the last decades. Within haematology, this includes studies on blood cell development and function and the intricate regulatory mechanisms within vertebrate immunity. Here, we review recent studies on the immediate mechanisms mounting an inflammatory response byin vivoanalyses using the zebrafish. These recently revealed novel roles of the reactive oxygen species hydrogen peroxide that have changed our view on the initiation of a granulocytic inflammatory response.
Diabetes and Thyroid Cancer Risk: Literature Review
Authors: Shih Shyang-Rong , Chiu Wei-Yih , Chang Tien-Chun , Tseng Chin-Hsiao
Published: June 2012

Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84–1.69) and was 0.96 (0.65–1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas.
Genetic Dissection of Marfan Syndrome and Related Connective Tissue Disorders: An Update 2012
Authors: Hoffjan S.
Published: June 2012

Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue characterized by early development of thoracic aortic aneurysms/dissections together with symptoms of the ocular and skeletal systems. While most patients/families with a classic phenotypic expression of MFS harbour mutations in the gene encoding fibrillin-1 (FBN1), genetic studies of the recent years revealed that the clinical features, as well as the mutated genes, show a high degree of overlap between MFS and other connective tissue diseases (e.g. Loeys-Dietz syndrome, Ehlers-Danlos syndrome, familial thoracic aneurysms and dissections and others). We summarize herein the current knowledge about the wide spectrum of differential diagnoses and their genetic background as well as novel therapeutic approaches in order to provide appropriate counselling and clinical follow-up for the patients.
Improvement of Endocardial and Vascular Endothelial Function on Myocardial Performance by Captopril Treatment in Postinfarct Rat Hearts
Authors: Qi Xiu-Ling , Stewart Duncan J. , Gosselin Hugues , Azad Azar , Picard Pierre , Andries Luc , Sys Stanislas U. , Brutsaert Dirk L. , Rouleau Jean L.
Published: June 2012

Background
—Endocardial (EE) and myocardial capillary vascular endothelial (myocap VE) cells have been shown to modulate the contractile characteristics of myocardium in a calcium-dependent manner. We evaluated the endothelial-myocardial interaction in the rat postinfarction myocardial infarction (MI) model and the effects of captopril.

Methods and Results
—Wistar rats were divided into 4 groups treated for 4 weeks: (1) control; (2) infarcted controls (left anterior coronary artery ligation); (3) infarcted+captopril 2 g/L in drinking water; and (4) infarct+captopril+triton intracoronary injection. Coronary VE function was evaluated by infusion of serotonin in Langendorff preparations (n=31), and the myocardial contractile characteristics were investigated by use of isolated papillary muscles (n=44). Cardiac mRNA for endothelial constitutive nitric oxide synthase (ecNOS) was measured, and its cellular location was evaluated by immunohistochemistry. Serotonin-induced increase in coronary flow was decreased in infarct controls compared with controls (4.6% versus 53.4%,
P
<0.01) but not in the 2 infarct+captopril groups. Intracoronary triton injection decreased serotonin-induced coronary flow in the infarct+captopril+triton group. All MI groups had decreased total tension in isolated papillary muscles. EE removal by triton immersion decreased total tension in all groups except for infarct controls (3.3 versus 3.2 g/mm
2
). Cardiac ecNOS mRNA decreased in the control infarct group but remained normal in the infarct+captopril group.

Conclusions
—Chronic postinfarction endothelium-induced coronary vasodilatation is impaired, and both EE and myocap VE dysfunction contribute to myocardial depression. Captopril use prevents these abnormalities and the reduction of cardiac ecNOS mRNA.
Total Complement Inhibition
Authors: Lazar Harold L. , Bao Yusheng , Gaudiani Jennifer , Rivers Samuel , Marsh Henry
Published: June 2012

Background
—Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium.

Methods and Results
—In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (ΔpH=−0.72±0.03 for unmodified; −0.46±0.05* for HB; −0.18±0.04*† for sCR1; −0.13±0.01*† for sCR1+HB), better recovery of wall motion scores (4=normal to −1=dyskinesia; 1.67±0.17 for unmodified; 2.80±0.08* for HB; 3.35±0.10*† for sCR1; 3.59±0.08*† for sCR1+HB), less lung water accumulation (5.46±0.28% for unmodified; 2.39±0.34%* for HB; 1.22±0.07%*† for sCR1; 1.24±0.13%*† for sCR1+HB), and smaller infarct size (area necrosis/area risk=44.6±0.7% for unmodified; 33.2±1.9%* for HB; 19.0±2.4%*† for sCR1; 20±1.0%*† for sCR1+HB) (*
P
<0.05 versus unmodified; †
P
<0.05 versus unmodified and HB groups).

Conclusions
—Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.
Long-Term Additive Prognostic Value of Thallium-201 Myocardial Perfusion Imaging Over Clinical and Exercise Stress Test in Low to Intermediate Risk Patients
Authors: Vanzetto Gérald , Ormezzano Olivier , Fagret Daniel , Comet Michel , Denis Bernard , Machecourt Jacques
Published: June 2012

Background
—The exercise treadmill test (ETT) and Tl201 single proton emission computed tomography (SPECT) are of short- to medium-term prognostic value in coronary heart disease. We assessed the long-term prognostic value of these tests in a large population of patients with low- to intermediate risk of cardiac events.

Methods and Results
—One thousand one hundred thirty-seven patients (857 men, age 55±9 years) referred for typical (62.1%) or atypical (22.4%) chest pain, or suspected silent ischemia (15.5%), were followed up for 72±18 months. Overall mortality was higher after strongly positive (ST depression >2 mm, or >1 mm for a workload ≤75 W) (2.36%/y) or nondiagnostic ETT (1.63%/y) than after normal (0.85%/y) or positive ETT (1.37%/y) (
P
=0.002), and after abnormal SPECT than after normal SPECT (1.60%/y versus 0.68%/y,
P
=0.001). The major cardiac event rate (cardiac death or myocardial infarction [MI]) was 0.88%, 1.59%, 2.10%, and 2.13%/y after negative, positive, strongly positive, and nondiagnostic ETT, respectively (
P
=0.003), and 0.56%, 1.43%, and 2.05%/y in patients with 0, 1 to 2, and ≥3 abnormal segments on SPECT, respectively (
P
<0.002). An abnormal SPECT was predictive of MI (
P
<0.001), whereas ETT was not. In multivariate analysis, SPECT was of incremental prognostic value over clinical and ETT data for predicting overall mortality and major cardiac events.

Conclusions
—The incremental predictive value of SPECT is maintained over 6 years and is particularly relevant after positive, strongly positive, and nondiagnostic ETT.
Dose-Response Effects of
32
P Radioactive Stents in an Atherosclerotic Porcine Coronary Model
Authors: Carter Andrew J. , Scott Douglas , Bailey Lynn , Hoopes Timothy , Jones Russ , Virmani Renu
Published: June 2012

Background
—Experimental studies have demonstrated that
32
P radioactive stents reduce neointimal formation at 28 days in porcine iliac and coronary arteries. Our objective was to determine the long-term dose-response effects of 1.0- to 12.0-μCi
32
P radioactive stents in a porcine atherosclerotic coronary model.

Methods and Results
—Control (n=19) and 1.0- to 12.0-μCi
32
P radioactive (n=43) stents (total, n=62) were implanted in the coronary arteries of 31 miniature swine at 28 days after creation of a fibrocellular plaque by overstretch balloon injury and cholesterol feeding. Angiography and histomorphometry were performed at 6 months. Stent thrombosis occurred in 3 radioactive (7.7%) and no control stents (
P
=0.54). On histology, the mean neointimal area and the percent in-stent stenosis correlated positively with increasing stent activity (
r
=0.64,
P
<0.001). The mean neointimal area (mm
2
) for the stents with ≥3.0 μCi
32
P (3.57±1.21) was significantly greater than that for the nonradioactive stents (1.78±0.68,
P
<0.0001). The neointima of the stents with ≥3.0 μCi
32
P was composed of smooth muscle cells, matrix proteoglycans, calcification, foam cells, and cholesterol clefts.

Conclusions
—Continuous low-dose-rate irradiation delivered by high-activity
32
P radioactive stents promotes the formation of an “atheromatous” neointima after 6 months in this experimental model. These data may be useful for predicting late tissue responses to radioactive stents in human coronary arteries.
Response of the Intact Canine Left Ventricle to Increased Afterload and Increased Coronary Perfusion Pressure in the Presence of Coronary Flow Autoregulation
Authors: Karunanithi Mohanraj K. , Young Jason A. , Kalnins Wally , Kesteven Scott , Feneley Michael P.
Published: June 2012

Background
—Increased left ventricular (LV) contractile force or oxygen consumption has been documented with increased coronary arterial pressure (CAP) and flow (Gregg phenomenon). We investigated whether the increase in contractile force with increased LV afterload might be mediated by the concomitant increase in CAP when coronary autoregulation is intact.

Methods and Results
—The LV of 6 autonomically blocked open-chest dogs was perfused through the left main coronary artery by a cannula with a side gate to the aortic root. With the gate open, CAP increased from 77±20 to 93±20 mm Hg (
P
<0.05) with aortic constriction (AC). With the gate closed, CAP was maintained at a constant level of 100 mm Hg. A small reduction in the slope of the preload recruitable stroke work (PRSW) relationship was observed with AC, but this response was not altered by the coronary perfusion gate position. The end-systolic pressure-volume (ESPV) relationship shifted upward significantly with AC (
P
<0.001), but this shift was not greater with open-gate perfusion than with closed-gate perfusion. Furthermore, with coronary autoregulation intact, wide changes in CAP (between 60 and 180 mm Hg, n=5) did not alter either the PRSW or ESPV relationship. In contrast, when autoregulation was abolished with intracoronary adenosine (n=6), both indexes of contractility increased progressively with increased CAP.

Conclusions
—The concomitant increase in CAP with increased afterload in the intact canine LV does not contribute to the afterload-induced increase in contractile force. Coronary perfusion pressure per se does not influence LV contractile function. Coronary perfusion pressure influences contractility only when coronary flow changes.
Transient Entrainment of Bundle-Branch Reentry by Atrial and Ventricular Stimulation
Authors: Merino Jose L. , Peinado Rafael , Fernández-Lozano Ignacio , Sobrino Nicolas , Sobrino Jose A.
Published: June 2012

Background
—Different responses to entrainment have been reported in relation to the pacing site of a variety of tachycardias. However, transient entrainment of bundle-branch reentrant tachycardia (BBRT) has not been investigated systematically.

Methods and Results
—We attempted entrainment of 13 BBRTs in 9 patients by pacing first the right ventricle and then the right atrium. The initial pacing cycle length (CL) was 10 ms faster than the tachycardia CL. Subsequent pacing sequences were performed with 5- to 10-ms CL decrements until tachycardia termination or loss of postatropine 1:1 AV conduction. Both full ventricular-paced and AV-conducted QRS complex references were obtained during sinus rhythm pacing from the same sites and with similar CL as during entrainment. Transient entrainment was achieved by ventricular and atrial stimulation in 11 and 8 tachycardias, respectively. Constant fusion was always present during entrainment by ventricular stimulation. There was no change in the QRS complex (orthodromically concealed fusion) during entrainment by atrial stimulation in 6 of 6 tachycardias with left bundle-branch block morphology and in 1 of 2 tachycardias with right bundle-branch block morphology.

Conclusions
—BBRT, especially if it has a left bundle-branch block morphology, can be differentiated from other wide-QRS-complex tachycardia mechanisms through analysis of the ECGs recorded during tachycardia entrainment by atrial and ventricular stimulation. This diagnostic approach may be especially useful when it is difficult to record a stable or sufficiently sized His bundle electrogram or when spontaneous changes in the ventricular CL precede similar changes in the His bundle CL.
Use of Electroanatomic Mapping to Delineate Transseptal Atrial Conduction in Humans
Authors: Roithinger Franz X. , Cheng Jie , SippensGroenewegen Arne , Lee Randall J. , Saxon Leslie A. , Scheinman Melvin M. , Lesh Michael D.
Published: June 2012

Background
—Interaction between wave fronts in the right and left atrium may be important for maintenance of atrial fibrillation, but little is known about electrophysiological properties and preferential routes of transseptal conduction.

Methods and Results
—Eighteen patients (age 44±12 years) without structural heart disease underwent right atrial electroanatomic mapping during pacing from the distal coronary sinus (CS) or the posterior left atrium. During distal CS pacing, 9 patients demonstrated a single transseptal breakthrough near the CS os, 1 patient in the high right atrium near the presumed insertion of Bachmann’s bundle and 1 patient near the fossa ovalis. The mean activation time from stimulus to CS os was 48±15 ms compared with 86±15 ms to Bachmann’s bundle insertion (
P
<0.01) and 59±23 ms to the fossa ovalis (
P
=NS and
P
<0.01, respectively). During left atrial pacing, the earliest right atrial activation was near Bachmann’s bundle in 5 and near the fossa ovalis in 4 patients. The activation time from stimulus to CS os was 70±15 ms compared with 47±16 ms to Bachmann’s bundle (
P
<0.01) and 59±25 ms to the fossa ovalis (
P
=NS). Whereas the total septal activation time was not significantly different during CS pacing compared with left atrial pacing (41±16 versus 33±17 ms), the total right atrial activation time was longer during CS pacing (117±49 versus 79±15 ms;
P
<0.05).

Conclusions
—Three distinct sites of early right atrial activation may be demonstrated during left atrial pacing. These sites are in accord with anatomic muscle bundles and may have relevance for maintenance of atrial flutter or fibrillation.
Electrical Remodeling of the Atria Following Loss of Atrioventricular Synchrony
Authors: Sparks Paul B. , Mond Harry G. , Vohra Jitendra K. , Jayaprakash Shenthar , Kalman Jonathan M.
Published: June 2012

Background
—Evidence suggests that an increased incidence of atrial fibrillation occurs in patients undergoing single-chamber ventricular pacing (VVI) when compared with those undergoing single-chamber atrial pacing (AAI) or those having dual-chamber atrioventricular pacing (DDD). The mechanism for this is unknown. We hypothesized that long-term loss of atrioventricular (AV) synchrony leads to atrial electrical remodeling: a potential explanation for this difference.

Methods and Results
—The study was a prospective, randomized comparison between 18 patients paced in VVI mode and 12 patients paced in DDD mode for 3 months. Under autonomic blockade, effective refractory periods (ERPs) from the lateral right atrium (RA), RA appendage, RA septum, and coronary sinus–corrected sinus node recovery times (cSNRTs), as well as P-wave duration (PWD), and biatrial diameters were measured at baseline and 3 months. The VVI group was then programmed to DDD pacing and reevaluated after a further 3 months. After long-term VVI pacing, ERPs at all 4 atrial sites increased significantly in a nonuniform fashion in association with biatrial dilatation. PWD and cSNRTs also prolonged significantly. With the reestablishment of AV synchrony, ERPs, PWD, cSNRTs, and biatrial dimensions returned to baseline levels. In the 12 patients who underwent long-term DDD pacing from baseline, no significant changes in atrial electrophysiology or biatrial dimensions were demonstrated.

Conclusions
—Long-term loss of AV synchrony induced by VVI pacing is associated with atrial electrical remodeling, which is reversible after the reestablishment of AV synchrony with DDD pacing. This process may be partly responsible for the higher incidence of atrial fibrillation in patients undergoing VVI pacing compared with AV sequential pacing.
Angiotensin II Activates Collagen Type I Gene in the Renal Vasculature of Transgenic Mice During Inhibition of Nitric Oxide Synthesis
Authors: Boffa Jean-Jacques , Tharaux Pierre-Louis , Placier Sandrine , Ardaillou Raymond , Dussaule Jean-Claude , Chatziantoniou Christos
Published: June 2012

Background
—Hypertension is frequently associated with renal vascular fibrosis. The purpose of this study was to investigate whether angiotensin II (Ang II) is involved in this fibrogenic process.

Methods and Results
—Experiments were performed on transgenic mice harboring the luciferase gene under the control of the collagen I-α
2
chain promoter [procolα
2
(I)]. Hypertension was induced by chronic inhibition of NO synthesis (
N
G
-nitro-
l
-arginine methyl ester, L-NAME). Procolα
2
(I) activity started to increase in the renal vasculature after 4 weeks of L-NAME treatment (
P
<0.01) and at 14 weeks reached 3- and 8-fold increases over control in afferent arterioles and glomeruli, respectively (
P
<0.001). Losartan, an AT
1
receptor antagonist, given simultaneously with L-NAME prevented the increase of procolα
2
(I) levels and attenuated the development of renal vascular fibrosis without normalizing systolic pressure increase. Because we found previously that endothelin mediated renal vascular fibrosis in the L-NAME model, the interaction between Ang II, endothelin, and procolα
2
(I) was investigated in ex vivo and short-term in vivo experiments. In both conditions, the Ang II–induced activation of procolα
2
(I) in renal cortex was blocked by an endothelin receptor antagonist.

Conclusions
—During chronic inhibition of NO, the collagen I gene becomes activated, leading to the development of renal vascular fibrosis. Ang II is a major player in this fibrogenic process, and its effect on collagen I gene is independent of systemic hemodynamics and is at least partly mediated by the profibrogenic action of endothelin.
Attainment and Maintenance of Platelet Inhibition Through Standard Dosing of Abciximab in Diabetic and Nondiabetic Patients Undergoing Percutaneous Coronary Intervention
Authors: Steinhubl Steven R. , Kottke-Marchant Kandice , Moliterno David J. , Rosenthal Monique L. , Godfrey Nikki K. , Coller Barry S. , Topol Eric J. , Lincoff A. Michael
Published: June 2012

Background
—Although the effectiveness of abciximab (c7E3 Fab; ReoPro) in large populations of patients undergoing a percutaneous coronary intervention has been consistently proved in clinical trials, it is unknown whether all patients achieve and maintain target inhibition during treatment. Diabetic patients in particular are a subgroup of patients with known underlying platelet abnormalities whose long-term response to abciximab has been shown to vary from that of nondiabetic patients.

Methods and Results
—Forty-nine diabetic and 51 nondiabetic patients who received adjunctive abciximab therapy during percutaneous coronary interventions were evaluated prospectively. The degree of platelet function inhibition was determined immediately after the abciximab bolus, 8 hours after the bolus (during the 12-hour abciximab infusion), and the next morning (13 to 26 hours after the bolus) with the use of a rapid platelet function assay (Accumetrics). After the abciximab bolus, platelet function was inhibited by 95±4% (mean±SD). By 8 hours, the average percent inhibition had decreased to 88±9%, with 13% of patients with <80% inhibition. The next morning (mean 19 hours after the bolus), mean inhibition was 71±14%. A difference was not found between diabetics and nondiabetics, nor was any physiological parameter found to be predictive of the response to abciximab.

Conclusions
—Although the majority of patients achieve and maintain ≥80% platelet inhibition during the 12-hour infusion with standard-dose abciximab, there is substantial variability among patients. Diabetic status does not appear to influence this variability.