bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans
Authors: Bailey Stephen J. , Fulford Jonathan , Vanhatalo Anni , Winyard Paul G. , Blackwell Jamie R. , DiMenna Fred J. , Wilkerson Daryl P. , Benjamin Nigel , Jones Andrew M.
Published: May 2010

The purpose of this study was to elucidate the mechanistic bases for the reported reduction in the O2cost of exercise following short-term dietary nitrate (NO3−) supplementation. In a randomized, double-blind, crossover study, seven men (aged 19–38 yr) consumed 500 ml/day of either nitrate-rich beetroot juice (BR, 5.1 mmol of NO3−/day) or placebo (PL, with negligible nitrate content) for 6 consecutive days, and completed a series of low-intensity and high-intensity “step” exercise tests on the last 3 days for the determination of the muscle metabolic (using31P-MRS) and pulmonary oxygen uptake (V̇o2) responses to exercise. On days 4–6, BR resulted in a significant increase in plasma [nitrite] (mean ± SE, PL 231 ± 76 vs. BR 547 ± 55 nM; P < 0.05). During low-intensity exercise, BR attenuated the reduction in muscle phosphocreatine concentration ([PCr]; PL 8.1 ± 1.2 vs. BR 5.2 ± 0.8 mM; P < 0.05) and the increase in V̇o2(PL 484 ± 41 vs. BR 362 ± 30 ml/min; P < 0.05). During high-intensity exercise, BR reduced the amplitudes of the [PCr] (PL 3.9 ± 1.1 vs. BR 1.6 ± 0.7 mM; P < 0.05) and V̇o2(PL 209 ± 30 vs. BR 100 ± 26 ml/min; P < 0.05) slow components and improved time to exhaustion (PL 586 ± 80 vs. BR 734 ± 109 s; P < 0.01). The total ATP turnover rate was estimated to be less for both low-intensity (PL 296 ± 58 vs. BR 192 ± 38 μM/s; P < 0.05) and high-intensity (PL 607 ± 65 vs. BR 436 ± 43 μM/s; P < 0.05) exercise. Thus the reduced O2cost of exercise following dietary NO3−supplementation appears to be due to a reduced ATP cost of muscle force production. The reduced muscle metabolic perturbation with NO3−supplementation allowed high-intensity exercise to be tolerated for a greater period of time.
Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type
Authors: Cadena Samuel M. , Tomkinson Kathleen N. , Monnell Travis E. , Spaits Matthew S. , Kumar Ravindra , Underwood Kathryn W. , Pearsall R. Scott , Lachey Jennifer L.
Published: May 2010

This is the first report that inhibition of negative regulators of skeletal muscle by a soluble form of activin type IIB receptor (ACE-031) increases muscle mass independent of fiber-type expression. This finding is distinct from the effects of selective pharmacological inhibition of myostatin (GDF-8), which predominantly targets type II fibers. In our study 8-wk-old C57BL/6 mice were treated with ACE-031 or vehicle control for 28 days. By the end of treatment, mean body weight of the ACE-031 group was 16% greater than that of the control group, and wet weights of soleus, plantaris, gastrocnemius, and extensor digitorum longus muscles increased by 33, 44, 46 and 26%, respectively ( P < 0.05). Soleus fiber-type distribution was unchanged with ACE-031 administration, and mean fiber cross-sectional area increased by 22 and 28% ( P < 0.05) in type I and II fibers, respectively. In the plantaris, a predominantly type II fiber muscle, mean fiber cross-sectional area increased by 57% with ACE-031 treatment. Analysis of myosin heavy chain (MHC) isoform transcripts by real-time PCR indicated no change in transcript levels in the soleus, but a decline in MHC I and IIa in the plantaris. In contrast, electrophoretic separation of total soleus and plantaris protein indicated that there was no change in the proportion of MHC isoforms in either muscle. Thus these data provide optimism that ACE-031 may be a viable therapeutic in the treatment of musculoskeletal diseases. Future studies should be undertaken to confirm that the observed effects are not age dependent or due to the relatively short study duration.
Daily training with high carbohydrate availability increases exogenous carbohydrate oxidation during endurance cycling
Authors: Cox Gregory R. , Clark Sally A. , Cox Amanda J. , Halson Shona L. , Hargreaves Mark , Hawley John A. , Jeacocke Nikki , Snow Rodney J. , Yeo Wee Kian , Burke Louise M.
Published: May 2010

We determined the effects of varying daily carbohydrate intake by providing or withholding carbohydrate during daily training on endurance performance, whole body rates of substrate oxidation, and selected mitochondrial enzymes. Sixteen endurance-trained cyclists or triathletes were pair matched and randomly allocated to either a high-carbohydrate group (High group; n = 8) or an energy-matched low-carbohydrate group (Low group; n = 8) for 28 days. Immediately before study commencement and during the final 5 days, subjects undertook a 5-day test block in which they completed an exercise trial consisting of a 100 min of steady-state cycling (100SS) followed by a 7-kJ/kg time trial on two occasions separated by 72 h. In a counterbalanced design, subjects consumed either water (water trial) or a 10% glucose solution (glucose trial) throughout the exercise trial. A muscle biopsy was taken from the vastus lateralis muscle on day 1 of the first test block, and rates of substrate oxidation were determined throughout 100SS. Training induced a marked increase in maximal citrate synthase activity after the intervention in the High group (27 vs. 34 μmol·g−1·min−1, P < 0.001). Tracer-derived estimates of exogenous glucose oxidation during 100SS in the glucose trial increased from 54.6 to 63.6 g ( P < 0.01) in the High group with no change in the Low group. Cycling performance improved by ∼6% after training. We conclude that altering total daily carbohydrate intake by providing or withholding carbohydrate during daily training in trained athletes results in differences in selected metabolic adaptations to exercise, including the oxidation of exogenous carbohydrate. However, these metabolic changes do not alter the training-induced magnitude of increase in exercise performance.
Detecting upper airway obstruction in patients with tracheal stenosis
Authors: Verbanck Sylvia , de Keukeleire Tom , Schuermans Daniël , Meysman Marc , Vincken Walter , Thompson Bruce
Published: May 2010

We propose a forced oscillation test modality for detecting upper airway obstruction (UAO) as an alternative to spirometric UAO indices in patients with tracheal stenosis. From oscillometry performed at different breathing flow rates, airway resistance at 5 Hz was determined at 0.5 l/s ( R), and flow dependence of resistance was computed as the regression slope of resistance vs. flow up to 1 l/s (Δ R/Δ V̇). It was first verified by measurement in 10 normal subjects and 10 patients with chronic obstructive pulmonary disease that Δ R/Δ V̇ was unaffected by the presence of peripheral airway obstruction and that external orifices (with lumen area down to 28 mm2) induced marked increases in R and Δ R/Δ V̇. Ten patients eligible for tracheal dilatation underwent spirometry and impulse oscillometry before and after intervention. Considering the lumen area of tracheal stenosis in the patients (42 ± 28 mm2, represented as the mean ± SD), the R and Δ R/Δ V̇ increases were of similar magnitude to those predicted by the external orifices. In addition, R ( r = −0.68; P = 0.001) and Δ R/Δ V̇ ( r = −0.65; P = 0.001) showed better correlations with minimal tracheal lumen than any spirometric UAO index. Δ R/Δ V̇, but not R, showed a consistent return to normal after intervention in the stenosis patients. We conclude that the forced oscillation test at different breathing flow rates up to 1 l/s provides a measure of UAO, namely flow dependence of resistance Δ R/Δ V̇, which can signal a critical level of tracheal stenosis and is not confounded by the presence of concomitant peripheral airway obstruction.
Results from a Phase I Clinical Study of the Novel Ii-Key/HER-2/neu(776–790) Hybrid Peptide Vaccine in Patients with Prostate Cancer
Authors: Perez Sonia A. , Kallinteris Nikoletta L. , Bisias Stratos , Tzonis Panagiotis K. , Georgakopoulou Katerina , Varla-Leftherioti Marighoula , Papamichail Michael , Thanos Anastasios , von Hofe Eric , Baxevanis Constantin N.
Published: May 2010

Purpose: Active immunotherapy is emerging as a potential therapeutic approach for prostate cancer. We conducted the first phase I trial of an Ii-Key/HER-2/neu(776–790) hybrid peptide vaccine (AE37) with recombinant granulocyte macrophage colony-stimulating factor as adjuvant in patients with HER-2/neu+ prostate cancer. The primary end points of the study were to evaluate toxicity and monitor patients' immune responses to the vaccine.

Experimental Design: Thirty-two HER-2/neu+, castrate-sensitive, and castrate-resistant prostate cancer patients were enrolled. Of these, 29 patients completed all six vaccination cycles with AE37. Immunologic responses in the total patient population were monitored by delayed-type hypersensitivity and IFN-γ ELISPOT and intracellular staining. Regulatory T-cell (Treg) frequency and plasma HER-2/neu and transforming growth factor-β levels were also determined. Immunologic responses were also analyzed among groups of patients with different clinical characteristics. Local/systemic toxicities were monitored throughout the study.

Results: Toxicities beyond grade 2 were not observed. Seventy-five percent of patients developed augmented immunity to the AE37 vaccine and 65% to the unmodified AE36 peptide as detected in the IFN-γ–based ELISPOT assay. Intracellular IFN-γ analyses revealed that AE37 elicited both CD4+ and CD8+ T-cell responses. Eighty percent of the patients developed a positive delayed-type hypersensitivity reaction to AE36. Additionally, significant decreases could be detected in circulating Treg frequencies, plasma HER-2/neu, and serum transforming growth factor-β levels. Patients with less extensive disease developed better immunologic responses on vaccination.

Conclusion: AE37 vaccine is safe and can induce HER-2/neu–specific cellular immune responses in patients with castrate-sensitive and castrate-resistant prostate cancer, thus emphasizing the potential of AE37 to target HER-2/neu for the immunotherapy of prostate cancer. Clin Cancer Res; 16(13); 3495–506. ©2010 AACR.
C-Reactive Protein and Risk of Venous Thromboembolism in the General Population
Authors: Zacho Jeppe , Tybjærg-Hansen Anne , Nordestgaard Børge G.
Published: May 2010

Objective—

To examine the robustness of the association between C-reactive protein (CRP) levels and increased risk of venous thromboembolism (VTE) and to examine whether genetically elevated CRP levels cause VTE.

Methods and Results—

In the prospective Copenhagen City Heart Study, we observed 10 388 participants for longer than 16 years, of whom 484 developed a VTE. In the cross-sectional Copenhagen General Population Study, we studied 36 616 participants, of whom 903 previously had a VTE. Levels of CRP greater than 3 mg/L versus less than 1 mg/L were associated with a 2.3- and 2.4-fold increased risk of VTE in the Copenhagen City Heart Study and the Copenhagen General Population Study, respectively. CRP levels in tertiles, quintiles, and octiles associated with a stepwise increase in VTE risk.
CRP
genotypes associated with an increase in plasma CRP levels up to 59% but did not associate consistently with risk of VTE in either study. The causal odds ratio for VTE for a doubling in genetically elevated CRP on instrumental variable analyses was lower than the odds ratio for VTE observed for a doubling in plasma CRP on logistic regression ([odds ratio and 95% CI] 0.80 [0.56 to 1.12] versus 1.17 [1.08 to 1.27];
P
=0.04).

Conclusion—

We observed 47 000 participants from the general population, of whom 1387 developed VTE. Although elevated CRP levels robustly associated with increased risk of VTE, this may not necessarily be a causal association because genetically elevated CRP did not associate with VTE risk.
Role of Delta-like-4/Notch in the Formation and Wiring of the Lymphatic Network in Zebrafish
Authors: Geudens Ilse , Herpers Robert , Hermans Karlien , Segura Inmaculada , Ruiz de Almodovar Carmen , Bussmann Jeroen , De Smet Frederik , Vandevelde Wouter , Hogan Benjamin M. , Siekmann Arndt , Claes Filip , Moore John C. , Pistocchi Anna Silvia , Loges Sonja , Mazzone Massimiliano , Mariggi Giovanni , Bruyère Françoise , Cotelli Franco , Kerjaschki Dontscho , Noël Agnes , Foidart Jean-Michel , Gerhardt Holger , Ny Annelii , Langenberg Tobias , Lawson Nathan D. , Duckers Henricus J. , Schulte-Merker Stefan , Carmeliet Peter , Dewerchin Mieke
Published: May 2010

Objective—

To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development.

Methods and Results—

In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch silencing reduced the number of sprouts producing the string of parchordal lymphangioblasts; instead, sprouts connecting to the intersomitic vessels were formed. At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates.

Conclusion—

These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network.
The Mouse Atherosclerosis Locus at Chromosome 10 (
Ath11
) Acts Early in Lesion Formation With Subcongenic Strains Delineating 2 Narrowed Regions
Authors: Wolfrum Susanne , Rodríguez José M. , Tan Marietta , Chen Kwan Y. , Teupser Daniel , Breslow Jan L.
Published: May 2010

Objective—

Ath11
, an atherosclerosis susceptibility locus on proximal chromosome 10 (0 to 21 cM) revealed in a cross between apolipoprotein E deficient C57BL/6 (B6) and FVB mice, was recently confirmed in congenic mice. The objectives of this study were to assess how
Ath11
affects lesion development and morphology, to determine aortic gene expression in congenics, and to narrow the congenic interval.

Methods and Results—

Assessing lesion area over time in congenic mice showed that homozygosity for the FVB allele increased lesion area at 6 weeks persisting through to 24 weeks of age. Staining of aortic root sections at 16 weeks did not reveal obvious differences between congenics. Aortic expression-array analysis at 6 weeks revealed 97 genes that were >2-fold regulated, including 1 gene in the quantitative trait locus interval,
Aldh8a1
, and 2 gene clusters regulated by
Hnf4α
and
Esr1
. Analysis of lesion area in 11 subcongenic strains revealed 2 narrowed regions, 10a (21 genes), acting in females, and 10b (7 genes), acting in both genders.

Conclusion—

Ath11
appears to act early in lesion formation, with significant effects on aortic gene expression. This quantitative trait locus is genetically complex, containing a female-specific region 10a from 0 to 7.3 megabases (21 genes) and a gender-independent region 10b from 20.1 to 21.9 megabases (7 genes).
Effects of High-Density Lipoproteins on Pancreatic β-Cell Insulin Secretion
Authors: Fryirs Michelle A. , Barter Philip J. , Appavoo Mathiyalagan , Tuch Bernard E. , Tabet Fatiha , Heather Alison K. , Rye Kerry-Anne
Published: May 2010

Objective—

Type 2 diabetes is characterized by impaired β-cell secretory function, insulin resistance, reduced high-density lipoprotein (HDL) levels, and increased cardiovascular risk. Given the current interest in therapeutic interventions that raise HDLs levels, this study investigates the effects of HDLs on insulin secretion from β-cells.

Methods and Results—

Incubation of Min6 cells and primary islets under basal or high-glucose conditions with either apolipoprotein (apo) A-I or apoA-II in the lipid-free form, as a constituent of discoidal reconstituted HDLs (rHDLs), or with HDLs isolated from human plasma increased insulin secretion up to 5-fold in a calcium-dependent manner. The increase was time and concentration dependent. It was also K
ATP
channel and glucose metabolism dependent under high-glucose, but not low-glucose, conditions. The lipid-free apolipoprotein-mediated increase in insulin secretion was ATP binding cassette (ABC) transporter A1 and scavenger receptor-B1 dependent. The rHDL-mediated increase in insulin secretion was ABCG1 dependent. Exposure of β-cells to lipid-free apolipoproteins also increased insulin mRNA expression and insulin secretion without significantly depleting intracellular insulin or cholesterol levels.

Conclusion—

These results establish that lipid-free and lipid-associated apoA-I and apoA-II increase β-cell insulin secretion and indicate that interventions that raise HDLs levels may be beneficial in type 2 diabetes.
Antithrombogenic Modification of Small-Diameter Microfibrous Vascular Grafts
Authors: Hashi Craig K. , Derugin Nikita , Janairo Randall Raphael R. , Lee Randall , Schultz David , Lotz Jeffrey , Li Song
Published: May 2010

Objective—

To develop small-diameter vascular grafts with a microstructure similar to native matrix fibers and with chemically modified microfibers to prevent thrombosis.

Methods and Results—

Microfibrous vascular grafts (1-mm internal diameter) were fabricated by electrospinning, and hirudin was conjugated to the poly (
l
-lactic acid) microfibers through an intermediate linker of poly(ethylene glycol). The modified microfibrous vascular grafts were able to reduce platelet adhesion/aggregation onto microfibrous scaffolds, and immobilized hirudin suppressed thrombin activity that may interact with the scaffolds. This 2-pronged approach to modify microfibrous vascular graft showed significantly improved patency (from 50% to 83%) and facilitated endothelialization, and the microfibrous structure of the vascular grafts allowed efficient graft remodeling and integration, with the improvement of mechanical property (elastic modulus) from 3.5 to 11.1 MPa after 6 months of implantation.

Conclusion—

Microfibrous vascular grafts with antithrombogenic microfibers can be used as small-diameter grafts, with excellent patency and remodeling capability.
Ventricular Dilation and Electrical Dyssynchrony Synergistically Increase Regional Mechanical Nonuniformity But Not Mechanical Dyssynchrony
Authors: Kerckhoffs Roy C.P. , Omens Jeffrey H. , McCulloch Andrew D. , Mulligan Lawrence J.
Published: May 2010

Background—

Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation.

Methods and Results—

All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97±0.004, 0.010±0.002, and 78±1 milliseconds, respectively. With dilation alone, CURE decreased 2.0±0.07%, ISF increased 58±47%, and WTpeak increased 31±3%. With dyssynchronous activation alone, CURE decreased 15±0.6%, ISF increased 14-fold (±3), and WTpeak increased 121±4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23±0.8%, ISF increased 20-fold (±5), and WTpeak increased 147±5%.

Conclusions—

Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.
Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake via p38α MAP Kinase–Mediated, Nitric Oxide–Dependent Mechanisms in Conscious Dogs With Dilated Cardiomyopathy
Authors: Bhashyam Siva , Fields Anjali V. , Patterson Brandy , Testani Jeffrey M. , Chen Li , Shen You-tang , Shannon Richard P.
Published: May 2010

Background—

We have shown that glucagon-like peptide-1 (GLP-1[7–36] amide) stimulates myocardial glucose uptake in dilated cardiomyopathy (DCM) independent of an insulinotropic effect. The cellular mechanisms of GLP-1–induced myocardial glucose uptake are unknown.

Methods and Results—

Myocardial substrates and glucoregulatory hormones were measured in conscious, chronically instrumented dogs at control (n=6), DCM (n=9) and DCM after treatment with a 48-hour infusion of GLP-1 (7–36) amide (n=9) or vehicle (n=6). GLP-1 receptors and cellular pathways implicated in myocardial glucose uptake were measured in sarcolemmal membranes harvested from the 4 groups. GLP-1 stimulated myocardial glucose uptake (DCM: 20±7 nmol/min/g; DCM+GLP-1: 61±12 nmol/min/g;
P
=0.001) independent of increased plasma insulin levels. The GLP-1 receptors were upregulated in the sarcolemmal membranes (control: 98±2 density units; DCM: 256±58 density units;
P
=0.046) and were expressed in their activated (65 kDa) form in DCM. The GLP-1–induced increases in myocardial glucose uptake did not involve adenylyl cyclase or Akt activation but was associated with marked increases in p38α MAP kinase activity (DCM+vehicle: 97±22 pmol ATP/mg/min; DCM+GLP-1: 170±36 pmol ATP/mg/min;
P
=0.051), induction of nitric oxide synthase 2 (DCM+vehicle: 151±13 density units; DCM+GLP-1: 306±12 density units;
P
=0.001), and GLUT-1 translocation (DCM+vehicle: 21±3% membrane bound; DCM+GLP-1: 39±3% membrane bound;
P
=0.005). The effects of GLP-1 on myocardial glucose uptake were blocked by pretreatment with the p38α MAP kinase inhibitor or the nonspecific nitric oxide synthase inhibitor nitro-
l
-arginine.

Conclusions—

GLP-1 stimulates myocardial glucose uptake through a non–Akt-1–dependent mechanism by activating cellular pathways that have been identified in mediating chronic hibernation and the late phase of ischemic preconditioning.
Cardioprotection of Ischemia/Reperfusion Injury by Cholesterol-Dependent MG53-Mediated Membrane Repair
Authors: Wang Xianhua , Xie Wenjun , Zhang Yi , Lin Peihui , Han Liang , Han Peidong , Wang Yanru , Chen Zheng , Ji Guangju , Zheng Ming , Weisleder Noah , Xiao Rui-Ping , Takeshima Hiroshi , Ma Jianjie , Cheng Heping
Published: May 2010

Rationale
:

Unrepaired cardiomyocyte membrane injury causes irreplaceable cell loss, leading to myocardial fibrosis and eventually heart failure. However, the cellular and molecular mechanisms of cardiac membrane repair are largely unknown. MG53, a newly identified striated muscle-specific protein, is involved in skeletal muscle membrane repair. But the role of MG53 in the heart has not been determined.

Objective
:

We sought to investigate whether MG53 mediates membrane repair in cardiomyocytes and, if so, the cellular and molecular mechanism underlying MG53-mediated membrane repair in cardiomyocytes. Moreover, we determined possible cardioprotective effect of MG53-mediated membrane repair.

Methods and Results
:

We demonstrated that MG53 is crucial to the emergency membrane repair response in cardiomyocytes and protects the heart from stress-induced loss of cardiomyocytes. Disruption of the sarcolemmal membrane by mechanical, electric, chemical, or metabolic insults caused rapid and robust translocation of MG53 toward the injury sites. Ablation of MG53 prevented sarcolemmal resealing after infrared laser–induced membrane damage in intact heart, and exacerbated mitochondrial dysfunction and loss of cardiomyocytes during ischemia/reperfusion injury. Unexpectedly, the MG53-mediated cardiac membrane repair was mediated by a cholesterol-dependent mechanism: depletion of membrane cholesterol abolished, and its recovery restored injury-induced membrane translocation of MG53. The redox status of MG53 did not affect initiation of MG53 translocation, whereas MG53 oxidation conferred stability to the membrane repair patch.

Conclusions
:

Thus, cholesterol-dependent MG53-mediated membrane repair is a vital, heretofore unappreciated cardioprotective mechanism against a multitude of insults and may bear important therapeutic implications.
Biphasic Development of the Mammalian Ventricular Conduction System
Authors: Miquerol Lucile , Moreno-Rascon Natividad , Beyer Sabrina , Dupays Laurent , Meilhac Sigolène M. , Buckingham Margaret E. , Franco Diego , Kelly Robert G.
Published: May 2010

Rationale
:

The ventricular conduction system controls the propagation of electric activity through the heart to coordinate cardiac contraction. This system is composed of specialized cardiomyocytes organized in defined structures including central components and a peripheral Purkinje fiber network. How the mammalian ventricular conduction system is established during development remains controversial.

Objective
:

To define the lineage relationship between cells of the murine ventricular conduction system and surrounding working myocytes.

Methods and Results
:

A retrospective clonal analysis using the α-cardiac actin

nlaacZ
/+

mouse line was carried out in three week old hearts. Clusters of clonally related myocytes were screened for conductive cells using
connexin40
-driven enhanced green fluorescent protein expression. Two classes of clusters containing conductive cells were obtained. Mixed clusters, composed of conductive and working myocytes, reveal that both cell types develop from common progenitor cells, whereas smaller unmixed clusters, composed exclusively of conductive cells, show that proliferation continues after lineage restriction to the conduction system lineage. Differences in the working component of mixed clusters between the right and left ventricles reveal distinct progenitor cell histories in these cardiac compartments. These results are supported by genetic fate mapping using Cre recombinase revealing progressive restriction of
connexin40
-positive myocytes to a conductive fate.

Conclusions
:

A biphasic mode of development, lineage restriction followed by limited outgrowth, underlies establishment of the mammalian ventricular conduction system.
Symptomatic Patients With Mild and Moderate Carotid Stenosis
Authors: Kwee Robert M. , van Oostenbrugge Robert J. , Prins Martin H. , ter Berg Johannes W.M. , Franke Cees L. , Korten Arthur G.G. C. , Meems Bé J. , van Engelshoven Jos M.A. , Wildberger Joachim E. , Mess Werner H. , Kooi M. Eline
Published: May 2010

Background and Purpose—

The objectives of this study were to assess plaque characteristics in symptomatic patients with mild and moderate carotid stenosis and to explore associations with cardiovascular risk factors and statin use.

Methods—

One hundred patients with transient ischemic attack or stroke with ipsilateral mild and moderate carotid stenosis underwent MR plaque imaging.

Results—

Patients with moderate stenosis had plaques with a higher prevalence of intraplaque hemorrhage (48.7% versus 19.7%,
P
=0.002) and a thin and/or ruptured fibrous cap (61.5% versus 36.1%,
P
=0.013), and larger lipid-rich necrotic core percentage (12.3% versus 6.8%,
P
=0.042) and smaller fibrous tissue percentage (82.7% versus 88.4%,
P
=0.024). Increasing age was positively associated with intraplaque hemorrhage (OR [per year]=1.08; 95% CI, 1.02 to 1.14;
P
=0.011). Statin use was negatively associated with intraplaque hemorrhage (OR=0.30; 95% CI, 0.10 to 0.93;
P
=0.038), a thin and/or ruptured fibrous cap (OR=0.34; 95% CI, 0.13 to 0.89;
P
=0.028), and with lipid-rich necrotic core percentage (B=−7.91; 95% CI, −13.60 to −2.22;
P
=0.007). Statin use was positively associated with fibrous tissue percentage (B=7.77; 95% CI, 2.40 to 13.14;
P
=0.005).

Conclusions—

We found that symptomatic patients with moderate stenosis have a higher prevalence of complicated plaques than patients with mild stenosis. Exploratory analysis showed that increasing age was positively associated with intraplaque hemorrhage, whereas statin use was negatively associated with complicated plaque features.
Beyond Dictatorship and Democracy: Rethinking National Minority Inclusion and Regime Type in Interwar Eastern Europe
Authors: Kopstein Jeffrey S. , Wittenberg Jason
Published: May 2010

Most standard models of democratization privilege class-based actors and the regimes they prefer to account for patterns of dictatorship and democracy. These models are ill suited, however, to explain political regime change in interwar Eastern Europe, where the dominant cleavage was not class but nationality. As a consequence, neither the process of regime change nor the resulting regime outcomes in Eastern Europe conform to the standard Western European models. Through a detailed analysis of key episodes of regime change in interwar Czechoslovakia and Poland, the authors explore the different ethnic and social coalitions on which political authority was built and the circumstances under which these two countries made the transition from one regime type to another. The depth of the ethnic divide meant that sustaining democracy in Eastern Europe required sidelining the urban bourgeoisie of the majority ethnic group from a dominant role in political life, a finding quite at odds with common views of the origins of democracy.
The Effect of Content Desirability on Subjective Video Quality Ratings
Authors: Kortum Philip , Sullivan Marc
Published: May 2010

Objective: The purpose of this study was to examine the impact of the desirability of content on viewers’ ratings of subjective video quality. Background: Most subjective video quality studies use short-duration clips that are specially designed to exercise the encoding algorithms and do not consider the desirability of the content as a variable. Method: In four studies, we employed a total of 100 participants and 180 movie clips encoded at nine levels from 550 kbps up to DVD quality. Participants viewed clips that were 2 min in length and then were asked about video quality of the clips and desirability of the movie content. Results: The results of these studies show that there is a strong correlation between the desirability of movie content and subjective ratings of video quality. This strong relationship holds across a wide range of encoding levels and movie content when that content is viewed under longer, more naturalistic viewing conditions. Conclusion: The effects of content should be considered when evaluating the subjective quality of encoded video content, as these effects can be as large as those seen between low- and high-quality encodings. Application: Researchers and practitioners trying to determine acceptable levels of video quality for actual consumption by consumers may find that the results and methods described here allow for a more accurate assessment of levels of video quality that are acceptable in a fielded service.
Multisensory Integration With a Head-Mounted Display: Background Visual Motion and Sound Motion
Authors: Harrison William J. , Thompson Matthew B. , Sanderson Penelope M.
Published: May 2010

Objective: The aim of this study was to assess how background visual motion and the relative movement of sound affect a head-mounted display (HMD) wearer’s performance at a task requiring integration of auditory and visual information. Background: HMD users are often mobile. A commercially available speaker in a fixed location delivers auditory information affordably to the HMD user. However, previous research has shown that mobile HMD users perform poorly at tasks that require integration of visual and auditory information when sound comes from a free-field speaker. The specific cause of the poor task performance is unknown. Method: Participants counted audiovisual events that required integration of sounds delivered via a free-field speaker and vision on an HMD. Participants completed the task while either walking around a room, sitting in the room, or sitting inside a mobile room that allowed separate manipulation of background visual motion and speaker motion. Results: Participants’ accuracy at counting target audiovisual events was worse when participants were walking than when sitting at a desk, p = .032. Compared with when they were sitting at a desk, participants’ accuracy at counting target audiovisual events showed a trend to be worse when they experienced a combination of background visual motion and the relative movement of sound, p = .058. Conclusion: Multisensory integration performance is least effective when HMD users experience a combination of background visual motion and relative movement of sound. Eye reflexes may play an important role. Application: Results apply to situations in which HMD wearers are mobile when receiving multimodal information, as in health care and military contexts.
Perceptions, Conceptions and Misconceptions of Organized Employment
Authors: Shulruf Boaz , Yee Beven , Lineham Brett , Fawthorpe Louise , Johri Roopali , Blumenfeld Stephen
Published: May 2010

The main objectives of this study were to identify facilitators and barriers to unionization among employees as well as to identify the effect of unionization and collective bargaining on employers’ and employees’ perceptions of workplace relations. To address these objectives survey data from just under 4000 employees and employers in over 150 New Zealand organizations was collected. The findings of this study suggest that union membership is related to employees’ perceptions of job security, ideology and job satisfaction. Employees’ perceptions of workplace relations were associated with union membership status. Employers’ perceptions of the contribution that unions make to their businesses were associated with the type of interaction employers had with trade unions. Implications for employees, employers, legislators and policy makers are discussed.
Academic Casualization in Australia: Class Divisions in the University
Authors: Brown Tony , Goodman James , Yasukawa Keiko
Published: May 2010

Casualization of teaching has become a major issue in Australian universities. In 1990 casuals delivered about a tenth of all university teaching. By 2008 between a third and a half of university teaching was being delivered by casuals. Quantitative studies have assessed the scale of casualization; this qualitative study addresses the experience of casual academics. It documents a sharpening class divide among academics, which has become institutionally embedded. It reports on interviews with casual academics examining how the divide is experienced, and how it may be addressed. Academic casuals report underpayment and compromised quality; they experience persistent income insecurity; and they find themselves voiceless in the workplace. These experiences are interpreted as aspects of class subordination, and possibilities for addressing them are discussed.
‘Comprehensive Campaigning’ in the NSW Transport Industry: Bridging the Divide Between Regulation and Union Organizing
Authors: Kaine Sarah , Rawling Michael
Published: May 2010

The transport industry in New South Wales is characterized by widespread precarious employment in the form of a workforce of truck owner-drivers who largely fall outside the scope of common law protections for employee drivers. A sizeable proportion of these contingent owner-drivers have been successfully organized to become active members of the New South Wales Transport Workers Union (TWU). This article briefly examines the industry structure within which this contingent workforce of truck owner-drivers has arisen. It analyses the strategic campaign strategy that underpins the leading role of this trade union in its (so far) successful struggle to obtain and maintain innovative regulatory protections providing substantial material benefits to this workforce, in the form of enforceable minimum working conditions. In so doing, the article demonstrates the considerable potential for union involvement in diverse regulatory frameworks, which may expand existing approaches to organizing and building union capacity.
Labour Discrimination as a Symptom of HIV: Experimental Evaluation - The Greek Case
Authors: Drydakis Nick
Published: May 2010

In the present study, we conducted the first ever Correspondence Test in order to test whether job applicants who voluntarily disclose their HIV infections face prejudices in the selection process in Greece. Resumes differing only in an applicant’s health status were faxed to advertised job openings. The outcomes imply that employers use health conditions as a factor when reviewing resumes. The rate of net discrimination against HIV-positive males was between 82.6 percent and 97.8 percent. Similarly, net discrimination against HIV-positive females was between 81.6 percent and 98.8 percent. Interestingly, the degree of discrimination was randomly assigned and unrelated to an applicant’s education level and job status. The current study develops a new methodology that could promote researchers worldwide to conduct similar surveys. As efforts to address HIV discrimination grow, so does the need for a set of standard discrimination indicators that have been tested and validated.
Exploring the Link Among Behavior Intervention Plans, Treatment Integrity, and Student Outcomes Under Natural Educational Conditions
Authors: Cook Clayton R. , Mayer G. Roy , Wright Diana Browning , Kraemer Bonnie , Wallace Michele D. , Dart Evan , Collins Tai , Restori Alberto
Published: May 2010

Several researchers have argued that the functional behavior assessment (FBA) and behavior intervention plan (BIP) mandates in the Individuals With Disabilities Education Act of 2004 have gone beyond the current research base. For instance, although BIPs have been shown to improve student outcomes when implemented with strict control and oversight by researchers, it is unclear whether these relationships hold true when implemented under real educational conditions. The purpose of this research was to conduct an initial study evaluating the relationship among the evidence-based quality of federally mandated BIPs, treatment integrity, and student outcomes under real-world educational conditions free from the help of researchers. Results indicated that the evidence-based quality of BIPs was significantly related to positive student outcomes. Results also supported the role of treatment integrity as a mediator of the relationship between the evidence-based quality of BIPs and student outcomes. The implications and limitations of this research as well as directions for future research are discussed.
Ethnic Differences in Autism Eligibility in the United States Public Schools
Authors: Morrier Michael J. , Hess Kristen L.
Published: May 2010

This study investigates ethnic differences for 295,945 children and youth with an autism eligibility reported to the U.S. Department of Education (USDOE) by 49 states plus the District of Columbia. Data analyses used relative difference, risk index, and risk ratio (RR). Results indicate that 80% of states report underrepresentation across ethnicities, with Hispanic children underrepresented in 95% of states. Use of developmental delay label was significantly related to disproportionate representation for school-age population ( F = 3.291, p = .046). Region of country yielded significant differences in RR for children classified as Asian ( F = 3.532, p = .014) and Caucasian ( F = 5.219, p = .002), for Black ( F = 4.355, p = .005) and Caucasian ( F = 2.840, p = .038) preschoolers, and for Asian ( F = 5.676, p = .001) and Caucasian ( F =4.906, p = .002) youth. Policy, training, and programming implications of the data are discussed.
Early Intervention Providers’ Perspectives About Implementing Participation-Based Practices
Authors: Fleming Jennifer L. , Sawyer L. Brook , Campbell Philippa H.
Published: May 2010

Early intervention providers submitted videotapes of home visits as part of requirements for a professional development course. Taped visits were classified into two practice groups: providers who demonstrated use of participation-based practices and those who did not (i.e., traditional practices). A sample of providers, selected from each of these groups, were interviewed to elicit perspectives about implementing participation-based practices. Findings indicate that providers, regardless of practice classification, did not fully understand participation-based practices. In particular, a provider role of promoting children’s participation in family/community activities and routines was not articulated. The caregiver’s role as facilitator of the child’s participation and learning was seldom described although the importance of involving, teaching, and supporting caregivers was acknowledged. Most providers described themselves as able to implement optimal services for only a small percentage of families and attributed both their ability and inability to family characteristics.
Diagnosing the Etiology of Hypercalcemia in a Dog
Authors: Sakals S. A. , Gillick M. S. , Kerr M. E. , Boston S. E.
Published: May 2010

A 13-year-old spayed Labrador Retriever cross dog presented for polyuria and polydipsia. Serum total calcium, free calcium, and intact parathyroid hormone concentrations were elevated. Surgical exploration of the ventral neck revealed a grossly enlarged right external parathyroid gland. The histopathological diagnosis for the excised right parathyroid gland was an incompletely resected parathyroid carcinoma. Parathyroid carcinoma in the dog is an infrequent cause of hypercalcemia and primary hyperparathyroidism.
A Morphological Study of 608 Cases of Canine Malignant Lymphoma in France With a Focus on Comparative Similarities Between Canine and Human Lymphoma Morphology
Authors: Ponce F. , Marchal T. , Magnol J. P. , Turinelli V. , Ledieu D. , Bonnefont C. , Pastor M. , Delignette M. L. , Fournel-Fleury C.
Published: May 2010

This study reports cytomorphological, histomorphological, and immunological characterization of 608 biopsy cases of canine malignant lymphoma, with epidemiological and clinical data, collected from 7 French veterinary pathology laboratories. It compares morphological characteristics of malignant lymphoma in canines, per the updated Kiel classification system, with those reported in humans, per the World Health Organization (WHO) classification system. Of tumors described, 24.5% and 75.5% were classified as low- and high-grade malignant lymphomas, respectively. Presenting clinical signs included generalized or localized lymphadenopathy (82.4%) and extranodal diseases (17.6%) involving the skin (12.34%) and other sites (5.26%). Immunohistochemistry confirmed 63.8% B-cell (CD3–, CD79a+), 35.4% T-cell (CD3+, CD79a–), and 0.8% null-cell (CD3–, CD79a–) lymphomas. Most B-cell cases (38.49%) were of high-grade centroblastic polymorphic subtype; most T-cell cases (8.55%), high-grade pleomorphic mixed and large T-cell lymphoma subtypes. Some B-cell tumors showed morphologic characteristics consistent with follicular lymphomas and marginal zone lymphomas per the Revised European American Classification of Lymphoid Neoplasms and WHO canine classification systems and the WHO human classification system. Unusual high-grade B-cell subtypes included an atypical high-grade small B-cell lymphoma (0.66%), Burkitt-type B-cell lymphoma (1.64%), plasmacytoid lymphoma (0.99%), and mediastinal anaplastic large B-cell lymphoma (0.16%). Unusual T-cell subtypes included a previously undescribed high-grade canine immunoblastic T-cell type (1.15%), a rare low-grade prolymphocytic T-cell lymphoma (0.16%), and a recently described high-grade canine T-cell entity—aggressive granulocytic large-cell lymphoma (0.16%). Marginal zone lymphomas were common (10.86%); follicular lymphomas were rare (0.49%). Canine primary cutaneous malignant lymphoma subtypes were present (11.84%). There was no significant difference between B- and T-cell malignant lymphoma in regard to canine age and sex. A significant overrepresentation of Boxers (24.19%) was found for T-cell lymphomas.
Outbreak of Neonatal Diarrhea in Farmed Mink Kits (Mustella vison) Associated With Enterotoxigenic Staphylococcus delphini
Authors: Sledge D. G. , Danieu P. K. , Bolin C. A. , Bolin S. R. , Lim A. , Anderson B. C. , Kiupel M.
Published: May 2010

An outbreak of diarrhea on a large commercial mink farm affected 5,000 of 36,000 neonatal mink kits, with 2,000 dying within a 2-week period. Affected kits were severely dehydrated, and their furcoats and paws were covered with yellow- to green-tinged mucoid feces. On necropsy, the small intestines of examined animals were markedly distended by serous to mucoid fluid. Microscopically, there was prominent colonization of the intestinal villar epithelium by gram-positive bacterial cocci in the absence of inflammation and morphologic changes in villous enterocytes. The colonizing bacteria were phenotypically identified as belonging to the Staphylococcus intermedius group of bacteria. This was confirmed by nucleic acid sequence analysis of the 16S ribosomal RNA gene. Further nucleic acid sequencing of polymerase chain reaction (PCR) amplicons from the superoxide dismutase gene and the heat shock protein 60 gene differentiated the isolate as Staphylococcus delphini. Production of staphylococcal enterotoxins A and E was demonstrated with a commercial ELISA-based immunoassay. Sequencing of PCR amplicons confirmed the presence of the enterotoxin E gene, but PCR amplification of the enterotoxin A, B, C, or D genes was not successful. Although direct causation was not confirmed in this study, the authors postulate that the observed hypersecretory diarrhea in these mink kits was the result of colonization of the small intestine by S delphini and subsequent production of enterotoxin.
Multicentric Squamous Cell Carcinoma In Situ Associated With Papillomavirus in a Ferret
Authors: Rodrigues A. , Gates L. , Payne H. R. , Kiupel M. , Mansell J.
Published: May 2010

A 6-year-old castrated male ferret presented with multiple black and tan proliferative skin lesions. Histologically, the lesions were characterized by multifocal plaques of irregular epidermal hyperplasia and full-thickness dysplasia, with loss of normal epithelial stratification, loss of nuclear polarity, and rare eosinophilic intranuclear inclusion bodies in the superficial layers of the epidermis. Immunohistochemical staining with a monoclonal antibody against papillomaviruses was strongly immunoreactive. Ultrastructurally, large numbers of hexagonal viral particles approximately 50 nm were observed within the nuclei of dysplastic superficial keratinocytes. To the authors' knowledge, this is the first report of a ferret multicentric squamous cell carcinoma in situ associated with papillomavirus.
Tularemia of European Brown Hare (Lepus europaeus)
Authors: Gyuranecz M. , Szeredi L. , Makrai L. , Fodor L. , Mészáros Á. R. , Szépe B. , Füleki M. , Erdélyi K.
Published: May 2010

The European brown hare ( Lepus europaeus) plays an important role in the ecology of tularemia, and it may serve as a significant source of human infection. The aim of the present study was to examine the lesions induced by Francisella tularensis in 50 cases of naturally infected seropositive European brown hares. Gross pathological examination revealed scant to numerous grayish-white foci with diameters of 0.1 to 1.0 cm in single organs (24 cases) or multiple organs (20 cases) in 44 of 50 cases (88%). These lesions proved to be areas of granulomatous inflammation, frequently encompassing necrosis. F tularensis antigen was detected with immunohistochemistry in 46 of 50 cases (92%), whereas F tularensis ssp holarctica was isolated by culture and identified by polymerase chain reaction from 35 of 50 cases (70%). Infection by the respiratory route is suggested by the presence of the tissue lesions in thoracic organs of 44 of 50 cases (88%). These results emphasize the importance of the European brown hare as a reservoir of tularemia.