bluuebunny/crossref_metadata_2025 huggingface dataset:
Clerodendrum inermeLeaf Extract Alleviates Animal Behaviors, Hyperlocomotion, and Prepulse Inhibition Disruptions, Mimicking Tourette Syndrome and Schizophrenia
Authors: Chen Hon-Lie , Lee Hsin-Jung , Huang Wei-Jan , Chou Jui-Feng , Fan Pi-Chuan , Du Jung-Chieh , Ku Yuan-Ling , Chiou Lih-Chu
Published: July 2012

Previously, we found a patient with intractable motor tic disorder, a spectrum of Tourette syndrome (TS), responsive to the ground leaf juice ofClerodendrum inerme(CI). Here, we examined the effect of the ethanol extract ofCIleaves (CIextract) on animal behaviors mimicking TS, hyperlocomotion, and sensorimotor gating deficit. The latter is also observed in schizophrenic patients and can be reflected by a disruption of prepulse inhibition of acoustic startle response (PPI) in animal models induced by methamphetamine and NMDA channel blockers (ketamine or MK-801), based on hyperdopaminergic and hypoglutamatergic hypotheses, respectively.CIextract (10–300 mg/kg,i.p.) dose-dependently inhibited hyperlocomotion induced by methamphetamine (2 mg/kg,i.p.) and PPI disruptions induced by methamphetamine, ketamine (30 mg/kg,i.p.), and MK-801 (0.3 mg/kg,i.p.) but did not affect spontaneous locomotor activity, rotarod performance, and grip force. These results suggest thatCIextract can relieve hyperlocomotion and improve sensorimotor gating deficit, supporting the therapeutic potential ofCIfor TS and schizophrenia.
Elevated Circulating Interleukin-27 in Patients with Coronary Artery Disease Is Associated with Dendritic Cells, Oxidized Low-Density Lipoprotein, and Severity of Coronary Artery Stenosis
Authors: Jin Wen , Zhao Yiqiao , Yan Wen , Cao Longxing , Zhang Weiwei , Wang Ming , Zhang Ting , Fu Qiang , Li Zhiliang
Published: July 2012

Coronary artery disease (CAD) is an immune-mediated chronic inflammatory disease mainly caused by atherosclerosis. The aims of this study were to investigate the role of interleukin-27 (IL-27) in patients with CAD and the severity of coronary artery lesions, which was evaluated by Gensini score and to investigate the biosynthesis of IL-27 and oxidized low-density lipoprotein (ox-LDL)in vitrousing monocyte-derived dendritic cells (DCs). To this aim, plasma levels of IL-27, ox-LDL, and Gensini score were analyzed in patients with CAD (n=136) and normal subjects (controls,n=29). IL-27 concentration of the supernatant and the mRNA expression levels of p28 and ebi3, subunits of IL-27, from cultured immature DCs incubated with different concentrations of ox-LDL for 24 h were also analyzed. We found that circulating IL-27 levels were significantly elevated in patients with CAD than in controls (P<0.01), and positively correlated to ox-LDL and Gensini score. ox-LDL dose-dependently upregulated expression of both IL-27 protein and IL-27 (p28 and EBI3) mRNAin vitro,indicating that ox-LDL can stimulate DCs to produce IL-27. These results demonstrate that IL-27 might regulate the network of immunity and inflammation in the pathogenesis of atherosclerosis.
Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies
Authors: Yang Qiong , Wang Yuanjia
Published: July 2012

Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical) or different types of components (e.g., some are continuous and others are categorical). We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.
Oxidative Stress and Epilepsy: Literature Review
Authors: Aguiar Carlos Clayton Torres , Almeida Anália Barbosa , Araújo Paulo Victor Pontes , Abreu Rita Neuma Dantas Cavalcante de , Chaves Edna Maria Camelo , Vale Otoni Cardoso do , Macêdo Danielle Silveira , Woods David John , Fonteles Marta Maria de França , Vasconcelos Silvania Maria Mendes
Published: July 2012

Backgrounds. The production of free radicals has a role in the regulation of biological function, cellular damage, and the pathogenesis of central nervous system conditions. Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. Experimental studies suggest that oxidative stress is a contributing factor to the onset and evolution of epilepsy.Objective. A review was conducted to investigate the link between oxidative stress and seizures, and oxidative stress and age as risk factors for epilepsy. The role of oxidative stress in seizure induction and propagation is also discussed.Results/Conclusions. Oxidative stress and mitochondrial dysfunction are involved in neuronal death and seizures. There is evidence that suggests that antioxidant therapy may reduce lesions induced by oxidative free radicals in some animal seizure models. Studies have demonstrated that mitochondrial dysfunction is associated with chronic oxidative stress and may have an essential role in the epileptogenesis process; however, few studies have shown an established link between oxidative stress, seizures, and age.
New Classes of Weighted Hölder-Zygmund Spaces and the Wavelet Transform
Authors: Pilipović Stevan , Rakić Dušan , Vindas Jasson
Published: July 2012

We provide a new and elementary proof of the continuity theorem for the wavelet and left-inverse wavelet transforms on the spaces𝒮0(ℝn)and𝒮(ℍn+1). We then introduce and study a new class of weighted Hölder-Zygmund spaces, where the weights are regularly varying functions. The analysis of these spaces is carried out via the wavelet transform and generalized Littlewood-Paley pairs.
On Guaranteed Detectability for Surveillance Sensor Networks
Authors: Zhu Yanmin
Published: July 2012

Surveillance is an important class of applications for wireless senor networks (WSNs), whose central task is to detect events of interest. Existing approaches seriously suffer from blind spots and low energy efficiency. In this paper, we propose a fully distributed algorithm GAP for energy-efficient event detection for surveillance applications. Employing the probabilistic approach, GAP actively tunes the active probability and minimizes the energy consumption of each sensor. The unique features of GAP are threefold. First, it provides guaranteed detectability for any event occurring in the sensing field. Second, it exposes a convenient interface of the user to specify the desired detectability. Finally, it supports differentiated service to empower better surveillance for critical spots. Without relying on costly time synchronization, GAP is a lightweight distributed protocol and is truly scalable to network scale and sensor density. Theoretical analysis and comprehensive simulation experiments are conducted, which jointly demonstrate that GAP is able to provide guaranteed detectability while significantly prolonging the system lifetime compared with other schemes.
The Radiology Fellowship Application and Selection Process in the United States: Experiences and Perceptions from Both Sides
Authors: Mulcahy Hyojeong , Chew Felix S. , Mulcahy Michael J.
Published: July 2012

Objective. Our purpose was to investigate radiology fellowship directors' and recent fellows' experiences and perceptions with regard to the fellowship application and selection process and to compare these experiences and perceptions.Materials and Methods. Institutional review board approval was obtained. We conducted an online survey of the memberships of three radiology subspecialty societies between October 2009 and December 2009 to learn about radiologists' views regarding various aspects of radiology fellowships.Results. In the process of selecting fellows, program directors and recent fellows consider performance during the radiology residency and the quality or prestige of the residency program as the most important objective factors, and the personal interview, letters of recommendation, and personality as the most important subjective factors. 25% of the program directors were in the match, and 41% of the recent fellows were in the match. Most (48%) of program directors favored a match, but most (56%) of the recent fellows disfavored participating in a match. Both program directors and recent fellows expressed satisfaction with the fellowship application and selection process.Conclusion. There was no majority support for a fellowship match among program directors and recent fellows and less support among recent fellows. Recent fellows appear more satisfied with the current selection and application process than program directors.
Determinants of Childhood Obesity in Representative Sample of Children in North East of Iran
Authors: Baygi Fereshteh , Dorosty Ahmad Reza , Kelishadi Roya , Qorbani Mostafa , Asayesh Hamid , Mansourian Morteza , Mirkarimi Kamal
Published: July 2012

Childhood obesity has become, a global public health problem, and epidemiological studies are important to identify its determinants in different populations. This study aimed to investigate factors associated with obesity in a representative sample of children in Neishabour, Iran. This study was conducted among 1500 randomly selected 6–12-year-old students from urban areas of Neishabour, northeast of Iran. Then, through a case-control study, 114 obese (BMI≥95th percentile of Iranian reference) children were selected as the case group and were compared with 102 controls (15th≤BMI<85th percentile). Factors suggested to be associated with weight status were investigated, for example, parental obesity, child physical activity levels, socio-economic status (SES), and so forth. The analysis was conducted using univariate and multivariate logistic regression (MLR) in SPSS version 16. In univariate logistic regression model, birth weight, birth order, family extension, TV watching, sleep duration, physical activity, parents’ job, parents’ education, parental obesity history, and SES were significantly associated with children’s obesity. After MLR analysis, physical activity and parental obesity history remained statistically significant in the model. Our findings showed that physical activity and parental obesity history are the most important determinants for childhood obesity in our population. This finding should be considered in implementation of preventive interventions.
Risk Factors for Mortality among 2009 A/H1N1 Influenza Hospitalizations in Maricopa County, Arizona, April 2009 to March 2010
Authors: Chowell G. , Ayala A. , Berisha V. , Viboud C. , Schumacher M.
Published: July 2012

We analyzed individual-level data on pandemic influenza A/H1N1pdm hospitalizations from the enhanced surveillance system of the Maricopa County Department of Public Health, AZ, USA from April 1st, 2009 to March 31st, 2010. We also assessed the the risk of death among A/H1N1 hospitalizations using multivariate logistic regression. Hospitalization rates were significantly higher among Native Americans (risk ratio (RR) = 6.2; 95% CI: 6.15, 6.21), non-Hispanic Black (RR = 3.84; 95% CI: 3.8, 3.9), and Hispanics (RR = 2.0; 95% CI: 2.0, 2.01) compared to non-Hispanic Whites. Throughout the spring, 59.2% of hospitalized patients received antiviral treatment; the proportion of patients treated increased significantly during the fall to 74.4% (Chi-square test,P<0.0001). In our best-fit logistic model, the adjusted risk of death among A/H1N1 inpatients was significantly higher during the fall wave (August 16, 2009 to March 31, 2010, OR = 3.94; 95% CI: 1.72, 9.03) compared to the spring wave (April 1, 2009 to August 15, 2009). Moreover, chronic lung disease (OR = 3.5; 95% CI: 1.7, 7.4), cancer within the last 12 months (OR = 4.3; 95%CI: 1.3, 14.8), immuno-suppression (OR = 4.0; 95% CI: 1.84, 8.9), and admission delays (OR = 4.6; 95% CI: 2.2, 9.5) were significantly associated with an increased the risk of death among A/H1N1 inpatients.
Characterization of Minimum Impeller Speed for Suspension of Solids in Liquid at High Solid Concentration, Using Gamma-Ray Densitometry
Authors: Jafari Rouzbeh , Tanguy Philippe A. , Chaouki Jamal
Published: July 2012

The successful design and operation of Liquid-Solid (LS) and Gas-Liquid-Solid (GLS) stirred tank reactors requires an accurate determination of the level of solid suspension needed for the process at hand. A poor design of the stirred tank to achieve optimum conditions and maintain the system under these conditions during operation may cause significant drawbacks concerning product quality (selectivity and yield) and cost. In this paper, the limitations of applying conventional measurement techniques for the accurate characterization of critical impeller speed for just off-bottom suspension (NJS) at high solid concentrations are described. Subsequently, the Gamma-Ray Densitometry technique for characterizingNJSis introduced, which can overcome the limitations of previous experimental techniques. The theoretical concept of this method is explained, and experimental validation is presented to confirm the accuracy of the Gamma-Ray Densitometry technique. The effects of clearance, scale, and solid loading onNJSfor several impellers are discussed. ExperimentalNJSvalues are compared with correlations proposed in the literatures, and modifications are made to improve the prediction. Finally, by utilizing the similarity to the incipient movement of solid particles in other systems, a theoretical model forNJSprediction is presented.
Functional Effects of GRM1 Suppression in Human Melanoma Cells
Authors: Wangari-Talbot Janet , Wall Brian A. , Goydos James S. , Chen Suzie
Published: July 2012

Ectopic expression of a neuronal receptor, metabotropic glutamate receptor 1 (Grm1), in melanocytes has been implicated in melanoma development in mouse models. The human relevance of this receptor's involvement in melanoma pathogenesis was shown by detecting GRM1 expression in subsets of human melanomas, an observation lacking in benign nevi or normal melanocytes. Grm1-transformed mouse melanocytes and a conditional Grm1 transgenic mouse model confirmed a requirement for sustained expression of Grm1 for the maintenance of transformed phenotypes in vitro and tumorigenicity in vivo. Here, we investigate if continued GRM1 expression is also required in human melanoma cell lines by using two inducible, silencing RNA systems: the ecdysone/Ponasterone A and tetracycline on/off approaches to regulate GRM1 expression in the presence of each inducer. Various in vitro assays were conducted to assess the consequences of a reduction in GRM1 expression on cell proliferation, apoptosis, downstream targeted signaling pathways, and in vivo tumorigenesis. We showed that suppression of GRM1 expression in several human melanoma cell lines resulted in a reduction in the number of viable cells and a decrease in stimulated mitogen-activated protein kinase (MAPK) and PI3K/AKT and suppressed tumor progression in vivo. These results reinforce earlier observations where a reduction in cell growth in vitro and tumorigenesis in vivo were correlated with decreased GRM1 activities by pharmacologic inhibitors of the receptor, supporting the notion that GRM1 plays a role in the maintenance of transformed phenotypes in human melanoma cells in vitro and in vivo and could be a potential therapeutic target for the treatment of melanoma. Mol Cancer Res; 10(11); 1440–50. ©2012 AACR.
RBM38 Is a Direct Transcriptional Target of E2F1 that Limits E2F1-Induced Proliferation
Authors: Feldstein Orit , Ben-Hamo Rotem , Bashari Dana , Efroni Sol , Ginsberg Doron
Published: July 2012

The E2F family of transcription factors plays a pivotal role in the regulation of cell proliferation in higher eukaryotes and is a critical downstream target of the tumor suppressor pRB. The pRB/E2F pathway is defective in most human tumors, resulting in deregulated E2F activity that induces uncontrolled cell proliferation, a hallmark of tumor cells.

The RNA-binding protein RBM38, also named RNPC1, induces cell-cycle arrest in G1, at least in part, via binding to and stabilizing the mRNA of the cyclin-dependent kinase inhibitor p21. RBM38 levels are altered in human cancer. Generally, RBM38 is overexpressed in various tumors; however, RBM38 mRNA levels are reduced in some breast tumors due to increased methylation of its promoter region.

We show here that expression of RBM38 is regulated by E2F1. Specifically, RBM38 mRNA and protein levels are elevated upon activation of either exogenous E2F1 or endogenous E2Fs. Moreover, endogenous E2F1 binds the human RBM38 promoter and E2F1 knockdown reduces RBM38 levels. Our data raise the possibility that E2F1 together with E2F1-regulated RBM38 constitute a negative feedback loop that modulates E2F1 activity. In support of this, inhibition of RBM38 expression increases E2F1-mediated cell-cycle progression. Moreover, in human ovarian cancer, high correlation between expression of E2F1 and RBM38 is associated with increased survival.

Overall, our data identify RBM38 as novel transcriptional target of E2F1 that restricts E2F1-induced proliferation. Furthermore, this negative feedback loop seems to restrict tumor aggressiveness, thereby promoting survival of patients with cancer. Mol Cancer Res; 10(9); 1169–77. ©2012 AACR.
Selective Hepatic Insulin Resistance, VLDL Overproduction, and Hypertriglyceridemia
Authors: Sparks Janet D. , Sparks Charles E. , Adeli Khosrow
Published: July 2012

Insulin plays a central role in regulating energy metabolism, including hepatic transport of very low-density lipoprotein (VLDL)–associated triglyceride. Hepatic hypersecretion of VLDL and consequent hypertriglyceridemia leads to lower circulating high-density lipoprotein levels and generation of small dense low-density lipoproteins characteristic of the dyslipidemia commonly observed in metabolic syndrome and type 2 diabetes mellitus. Physiological fluctuations of insulin modulate VLDL secretion, and insulin inhibition of VLDL secretion upon feeding may be the first pathway to become resistant in obesity that leads to VLDL hypersecretion. This review summarizes the role of insulin–related signaling pathways that determine hepatic VLDL production. Disruption in signaling pathways that reduce generation of the second messenger phosphatidylinositide (3,4,5) triphosphate downstream of activated phosphatidylinositide 3-kinase underlies the development of VLDL hypersecretion. As insulin resistance progresses, a number of pathways are altered that further augment VLDL hypersecretion, including hepatic inflammatory pathways. Insulin plays a complex role in regulating glucose metabolism, and it is not surprising that the role of insulin in VLDL and lipid metabolism will prove equally complex.
Intima-Media Thickness of Brachial Artery, Vascular Function, and Cardiovascular Risk Factors
Authors: Iwamoto Yumiko , Maruhashi Tatsuya , Fujii Yuichi , Idei Naomi , Fujimura Noritaka , Mikami Shinsuke , Kajikawa Masato , Matsumoto Takeshi , Kihara Yasuki , Chayama Kazuaki , Noma Kensuke , Nakashima Ayumu , Higashi Yukihito
Published: July 2012

Objective—

Cardiovascular diseases are associated with impaired flow-mediated vasodilation (FMD) and increase in carotid intima-media thickness (IMT). Both FMD and IMT are independent predictors for cardiovascular outcomes. When measuring FMD and nitroglycerine-induced vasodilation in the brachial artery, IMT can also be simultaneously assessed in the same brachial artery. The purpose of this study was to determine the relationships between IMT of the brachial artery, vascular function, and cardiovascular risk factors.

Methods and Results—

We measured brachial IMT, FMD, and nitroglycerine-induced vasodilation by ultrasound in 388 subjects who underwent health examination (mean age, 45±22 years; age range, 19–86), including patients with cardiovascular diseases. Univariate regression analysis revealed that brachial IMT significantly correlated with age (
r
=0.71;
P
<0.001), body mass index (
r
=0.27;
P
<0.001), systolic blood pressure (
r
=0.40;
P
<0.001), diastolic blood pressure (
r
=0.31;
P
<0.001), heart rate (
r
=0.15;
P
=0.002), glucose level (
r
=0.18;
P
=0.01), and smoking pack-years (
r
=0.42;
P
<0.001), as well as Framingham risk score, a cumulative cardiovascular risk index for heart attack (
r
=0.49;
P
<0.001). FMD and nitroglycerine-induced vasodilation were inversely associated with brachial IMT (
r
=−0.39,
P
<0.001;
r
=−0.32,
P
<0.001, respectively). In addition, there was a significant relationship between brachial IMT and carotid IMT (
r
=0.58;
P
<0.001). Multivariate analysis revealed that age, sex, hypertension, and brachial artery diameter were independent predictors of brachial IMT.

Conclusion—

These findings suggest that brachial IMT may be a marker of the grade of atherosclerosis and may be used as a marker of vascular function, providing additive information for stratifying subjects with cardiovascular risk factors.
Thrombomodulin Protects Endothelial Cells From a Calcineurin Inhibitor–Induced Cytotoxicity by Upregulation of Extracellular Signal–Regulated Kinase/Myeloid Leukemia Cell-1 Signaling
Authors: Ikezoe Takayuki , Yang Jing , Nishioka Chie , Honda Goichi , Furihata Mutsuo , Yokoyama Akihito
Published: July 2012

Objective—

We have recently reported that recombinant human soluble thrombomodulin (rTM) counteracted capillary leakage associated with engraftment, as well as sinusoidal obstructive syndrome after hematopoietic stem cell transplantation. These observations prompted us to explore whether rTM possessed cytoprotective effects on endothelial cells.

Methods and Results—

Exposure of human umbilical vein endothelial cells to rTM induced expression of antiapoptotic protein myeloid leukemia cell-1 through the activation of extracellular signal–regulated kinase in these cells. Additional studies found that exposure of human umbilical vein endothelial cells to cyclosporine A and FK506, an immunosuppressant used for the individuals receiving hematopoietic stem cell transplantation, induced apoptosis, which was attenuated when human umbilical vein endothelial cells were exposed to these agents in the presence of rTM. Further studies using deletion mutants of thrombomodulin (TM) identified that the epidermal growth factor domain of TM possessed cytoprotective effects. A single nucleotide substitution at codon 376 or 424 of TM, which impairs the ability of TM to produce activated protein C or bind to thrombin, respectively, did not hamper the cytoprotective effects of TM, which suggested that cytoprotective effects of rTM were distinctive from those of activated protein C.

Conclusion—

TM may be useful for prevention, as well as treatment of endothelial cell damage after hematopoietic stem cell transplantation.
Mineralocorticoid Receptor Antagonists and Cardiovascular Mortality in Patients With Atrial Fibrillation and Left Ventricular Dysfunction
Authors: O’Meara Eileen , Khairy Paul , Blanchet Malorie Chabot , de Denus Simon , Pedersen Ole D. , Levesque Sylvie , Talajic Mario , Ducharme Anique , White Michel , Racine Normand , Rouleau Jean-Lucien , Tardif Jean-Claude , Roy Denis ,   and for the AF-CHF investigators
Published: July 2012

Background—

Patients with heart failure (HF) and atrial fibrillation (AF) may differ from the larger HF population with respect to comorbidities, including renal impairment and overall prognosis. Associated cardiorenal interactions may mitigate the effects of pharmacological agents. Our primary objective was to assess the impact of mineralocorticoid receptor antagonists on cardiovascular mortality in patients with AF and HF enrolled in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial.

Methods and Results—

All 1376 patients randomized in the AF-CHF trial were included. The median baseline creatinine was 105.2 (Q1 88.4, Q3 125.0) μmol/L, and the median estimated glomerular filtration rate was 62.3 (Q1 49.0, Q3 77.2) mL/min per 1.73 m
2
. The renal function was moderately or severely impaired (ie, estimated glomerular filtration rate <60 mL/min per 1.73 m
2
) in 46.5% of patients. In multivariable analyses, increased creatinine was associated with worsening HF but not mortality. Mineralocorticoid receptor antagonists were prescribed in 44.8% and were independently associated with a 1.4-fold increase in total mortality (hazard ratio, 1.4; 95% CI [1.1–1.8];
P
=0.005) and a 1.4-fold increase in cardiovascular mortality (hazard ratio, 1.4; 95% CI [1.1–1.9];
P
=0.009). This was driven by an increased incidence of sudden cardiac death (hazard ratio, 2.0; 95% CI [1.3, 3.0];
P
=0.001).

Conclusions—

Renal dysfunction was highly prevalent in patients with AF and HF. Mineralocorticoid receptor antagonists were independently associated with an increased incidence of cardiovascular deaths, predominantly of presumed arrhythmic cause. Although these provocative findings merit prospective validation, they underscore the importance of careful monitoring of renal function and electrolytes in patients with AF and HF receiving mineralocorticoid receptor antagonists.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00597077.
Hemodynamic, Hormonal, and Renal Effects of (Pro)Renin Receptor Blockade in Experimental Heart Failure
Authors: Rademaker Miriam T. , Yandle Tim G. , Ellmers Leigh J. , Charles Christopher J. , Nicholls M. Gary , Richards A. Mark
Published: July 2012

Background—

The (pro)renin receptor (P)RR is implicated in blood pressure regulation and the pathophysiology of heart failure (HF). The effects of (P)RR blockade in HF have not been previously investigated.

Methods and Results—

Eight sheep received on 2 separate days a vehicle control and incremental intravenous boluses of a (P)RR antagonist, ovine handle region peptide (HRP) (1, 5, and 25 mg at 90-minute intervals), both before (normal) and after induction of HF by rapid left ventricular pacing. In normal sheep, HRP reduced heart rate (
P
<0.001) and hematocrit (
P
=0.019) compared with time-matched control data, without significantly affecting any other hemodynamic, hormonal, or renal variables. In sheep with HF, HRP treatment induced progressive falls in mean arterial pressure (
P
<0.001) in association with decreases in left atrial pressure (
P
<0.001), peripheral resistance (
P
=0.014), and hematocrit (
P
<0.001). Cardiac contractility tended to decline (
P
=0.096), whereas cardiac output was unaltered. HRP administration produced a dose-dependent decrease in plasma renin activity (
P
=0.004), with similar trends observed for plasma angiotensin II and aldosterone (
P
=0.093 and
P
=0.088, respectively). Circulating natriuretic peptides, endothelin-1, and catecholamine levels were unchanged. HRP also induced a reduction in plasma sodium concentrations relative to control (
P
=0.024), a natriuresis (
P
=0.046), and a tendency for creatinine excretion and clearance to improve.

Conclusions—

(P)RR antagonism in experimental HF resulted in cardiovascular and renal benefits in association with inhibition of the renin-angiotensin-aldosterone system. These findings suggest that (P)RR contributes to pressure/volume regulation in HF and identifies the receptor as a potential therapeutic target in this disease.
Evaluation of Aortic Valve Stenosis Using Cardiovascular Magnetic Resonance
Authors: Defrance Carine , Bollache Emilie , Kachenoura Nadjia , Perdrix Ludivine , Hrynchyshyn Nataliya , Bruguière Eric , Redheuil Alban , Diebold Benoit , Mousseaux Elie
Published: July 2012

Background—

Accurate quantification of aortic valve stenosis (AVS) is needed for relevant management decisions. However, transthoracic Doppler echocardiography (TTE) remains inconclusive in a significant number of patients. Previous studies demonstrated the usefulness of phase-contrast cardiovascular magnetic resonance (PC-CMR) in noninvasive AVS evaluation. We hypothesized that semiautomated analysis of aortic hemodynamics from PC-CMR might provide reproducible and accurate evaluation of aortic valve area (AVA), aortic velocities, and gradients in agreement with TTE.

Methods and Results—

We studied 53 AVS patients (AVA
TTE
=0.87±0.44 cm
2
) and 21 controls (AVA
TTE
=2.96±0.59 cm
2
) who had TTE and PC-CMR of aortic valve and left ventricular outflow tract on the same day. PC-CMR data analysis included left ventricular outflow tract and aortic valve segmentation, and extraction of velocities, gradients, and flow rates. Three AVA measures were performed: AVA
CMR1
based on Hakki formula, AVA
CMR2
based on continuity equation, AVA
CMR3
simplified continuity equation=left ventricular outflow tract peak flow rate/aortic peak velocity. Our analysis was reproducible, as reflected by low interoperator variability (<4.56±4.40%). Comparison of PC-CMR and TTE aortic peak velocities and mean gradients resulted in good agreement (
r
=0.92 with mean bias=−29±62 cm/s and
r
=0.86 with mean bias=−12±15 mm Hg, respectively). Although good agreement was found between TTE and continuity equation–based CMR-AVA (
r
>0.94 and mean bias=−0.01±0.38 cm
2
for AVA
CMR2
, −0.09±0.28 cm
2
for AVA
CMR3
), AVA
CMR1
values were lower than AVA
TTE
especially for higher AVA (mean bias=−0.45±0.52 cm
2
). Besides, ability of PC-CMR to detect severe AVS, defined by TTE, provided the best results for continuity equation–based methods (accuracy >94%).

Conclusions—

Our PC-CMR semiautomated AVS evaluation provided reproducible measurements that accurately detected severe AVS and were in good agreement with TTE.
Cardiomyocyte GTP Cyclohydrolase 1 and Tetrahydrobiopterin Increase NOS1 Activity and Accelerate Myocardial Relaxation
Authors: Carnicer Ricardo , Hale Ashley B. , Suffredini Silvia , Liu Xing , Reilly Svetlana , Zhang Mei Hua , Surdo Nicoletta C. , Bendall Jennifer K. , Crabtree Mark J. , Lim Gregory B.S. , Alp Nicholas J. , Channon Keith M. , Casadei Barbara
Published: July 2012

Rationale:

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOS). Oral BH4 supplementation preserves cardiac function in animal models of cardiac disease; however, the mechanisms underlying these findings are not completely understood.

Objective:

To study the effect of myocardial transgenic overexpression of the rate-limiting enzyme in BH4 biosynthesis, GTP cyclohydrolase 1 (GCH1), on NOS activity, myocardial function, and Ca
2+
handling.

Methods and Results:

GCH1
overexpression significantly increased the biopterins level in left ventricular (LV) myocytes but not in the nonmyocyte component of the LV myocardium or in plasma. The ratio between BH4 and its oxidized products was lower in mGCH1-Tg, indicating that a large proportion of the myocardial biopterin pool was oxidized; nevertheless, myocardial NOS1 activity was increased in mGCH1-Tg, and superoxide release was significantly reduced. Isolated hearts and field-stimulated LV myocytes (3 Hz, 35°C) overexpressing
GCH1
showed a faster relaxation and a PKA-mediated increase in the PLB Ser
16
phosphorylated fraction and in the rate of decay of the [Ca
2+
]
i
transient. RyR2 S-nitrosylation and diastolic Ca
2+
leak were larger in mGCH1-Tg and
I
Ca
density was lower; nevertheless the amplitude of the [Ca
2+
]
i
transient and contraction did not differ between genotypes, because of an increase in the SR fractional release of Ca
2+
in mGCH1-Tg myocytes. Xanthine oxidoreductase inhibition abolished the difference in superoxide production but did not affect myocardial function in either group. By contrast, NOS1 inhibition abolished the differences in
I
Ca
density, Ser
16
PLB phosphorylation, [Ca
2+
]
i
decay, and myocardial relaxation between genotypes.

Conclusions:

Myocardial GCH1 activity and intracellular BH4 are a limiting factor for constitutive NOS1 and SERCA2A activity in the healthy myocardium. Our findings suggest that GCH1 may be a valuable target for the treatment of LV diastolic dysfunction.
Development of a Clinical Score (A
2
DS
2
) to Predict Pneumonia in Acute Ischemic Stroke
Authors: Hoffmann Sarah , Malzahn Uwe , Harms Hendrik , Koennecke Hans-Christian , Berger Klaus , Kalic Marianne , Walter Georg , Meisel Andreas , Heuschmann Peter Ulrich
Published: July 2012

Background and Purpose—

Poststroke pneumonia is a potentially preventable complication after stroke associated with poor outcome. We developed and externally validated a prognostic score for predicting risk of pneumonia after ischemic stroke.

Methods—

The prognostic score was developed based on clinical data routinely collected after admission from the Berlin Stroke Register, Germany. The association of demographics, comorbidities, and clinical characteristics with poststroke pneumonia was investigated using multivariable logistic regression analyses. Independent predictors of poststroke pneumonia were translated into a point scoring system based on the corresponding regression coefficients. The predictive properties of the developed prognostic score were externally validated using an independent data set from the Stroke Register Northwest-Germany.

Results—

Between 2007 and 2009, 15 335 patients with ischemic stroke were registered within the Berlin Stroke Register. The observed rate of pneumonia in hospital was 7.2%. A 10-point score was derived for prediction of poststroke pneumonia (Age ≥75 years=1, Atrial fibrillation=1, Dysphagia=2, male Sex=1, stroke Severity, National Institutes of Health Stroke Scale 0–4=0, 5–15=3, ≥16=5; A
2
DS
2
). The proportion of pneumonia varied between 0.3% in patients with a score of 0 point to 39.4% in patients with a score of 10 points. The score demonstrated excellent discrimination (C-statistic 0.84; 95% CI, 0.83–0.85) and calibration (McFadden
R
2
=0.21). Prediction, discrimination, and calibration properties were reproduced in the validation cohort consisting of 45 085 patients with ischemic stroke.

Conclusions—

The A
2
DS
2
score is a valid tool for predicting poststroke pneumonia based on routinely available data. A
2
DS
2
might be useful for guiding monitoring of high-risk patients or prophylactic pneumonia management in clinical routine.
Higher Plasma Fractalkine Is Associated With Better 6-Month Outcome From Ischemic Stroke
Authors: Donohue Megan M. , Cain Kevin , Zierath Dannielle , Shibata Dean , Tanzi Patricia M. , Becker Kyra J.
Published: July 2012

Background and Purpose—

Fractalkine (CX3CL1) is a unique chemokine that is constitutively expressed on neurons where it serves as an adhesion molecule for lymphocytes and monocytes. CX3CL1 may also be cleaved from the surface of these cells and enter the circulation to act as a traditional chemokine. CX3CL1 could thus influence the inflammatory response after stroke. We hypothesized that patients with higher plasma CX3CL1 after stroke would have a more robust inflammatory response and experience worse outcome.

Methods—

Plasma CX3CL1 concentrations were assessed in 85 patients who were part of a larger study evaluating immune responses after ischemic stroke; CX3CL1 values were available from Day 1 to Day 180 after stroke onset. CX3CL1 was correlated to measures of inflammation and its effect on outcome assessed.

Results—

At 1 day after stroke, CX3CL1 was lower in patients with severe strokes. At 180 days after stroke, CX3CL1 concentrations were lower in patients with poor outcome. The association of CX3CL1 and outcome at 180 days was independent of initial stroke severity. Plasma CX3CL1 at 180 days was inversely associated with systemic markers of inflammation, including white blood cell counts and high-sensitivity C-reactive protein.

Conclusions—

In contrast to our original hypothesis, lower concentrations of CX3CL1 are associated with worse stroke outcome. In light of recent studies suggesting an immunomodulatory and neuroprotective role for CX3CL1 in a variety of neurodegenerative diseases, a therapeutic role for CX3CL1 in stroke recovery should be considered.
Spectrum of Transient Focal Neurological Episodes in Cerebral Amyloid Angiopathy
Authors: Charidimou Andreas , Peeters Andre , Fox Zoe , Gregoire Simone M. , Vandermeeren Yves , Laloux Patrice , Jäger Hans R. , Baron Jean-Claude , Werring David J.
Published: July 2012

Background and Purpose—

Transient focal neurological episodes (TFNE) are recognized in cerebral amyloid angiopathy (CAA) and may herald a high risk of intracerebral hemorrhage (ICH). We aimed to determine their prevalence, clinical neuroimaging spectrum, and future ICH risk.

Methods—

This was a multicenter retrospective cohort study of 172 CAA patients. Clinical, imaging, and follow-up data were collected. We classified TFNE into: predominantly positive symptoms (“aura-like” spreading paraesthesias/positive visual phenomena or limb jerking) and predominantly negative symptoms (“transient ischemic attack–like” sudden-onset limb weakness, dysphasia, or visual loss). We pooled our results with all published cases identified in a systematic review.

Results—

In our multicenter cohort, 25 patients (14.5%; 95% confidence interval, 9.6%–20.7%) had TFNE. Positive and negative symptoms were equally common (52% vs 48%, respectively). The commonest neuroimaging features were leukoaraiosis (84%), lobar ICH (76%), multiple lobar cerebral microbleeds (58%), and superficial cortical siderosis/convexity subarachnoid hemorrhage (54%). The CAA patients with TFNE more often had superficial cortical siderosis/convexity subarachnoid hemorrhage (but not other magnetic resonance imaging features) compared with those without TFNE (50% vs 19%;
P
=0.001). Over a median period of 14 months, 50% of TFNE patients had symptomatic lobar ICH. The meta-analysis showed a risk of symptomatic ICH after TFNE of 24.5% (95% confidence interval, 15.8%–36.9%) at 8 weeks, related neither to clinical features nor to previous symptomatic ICH.

Conclusions—

TFNE are common in CAA, include both positive and negative neurological symptoms, and may be caused by superficial cortical siderosis/convexity subarachnoid hemorrhage. TFNE predict a high early risk of symptomatic ICH (which may be amenable to prevention). Blood-sensitive magnetic resonance imaging sequences are important in the investigation of such episodes.
Impact of Acute Ischemic Stroke Treatment in Patients >80 Years of Age
Authors: Willey Joshua Z. , Ortega-Gutierrez Santiago , Petersen Nils , Khatri Pooja , Ford Andria L. , Rost Natalia S. , Ali Latisha K. , Gonzales Nichole R. , Merino Jose G. , Meyer Brett C. , Marshall Randolph S.
Published: July 2012

Background and Purpose—

Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA).

Methods—

Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged ≥80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age ≥80 years using multivariable logistic regression. An age-stratified analysis was also performed.

Results—

A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients ≥80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60–2.84). When limited to those aged ≥80 years, IAT (OR, 0.95; 95% CI, 0.60–1.49), bridging therapy (OR, 0.82; 95% CI, 0.47–1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64–2.08) versus IV rtPA were not associated with increased in-hospital mortality.

Conclusions—

IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone.
Cortical Changes After Mental Imagery Training Combined With Electromyography-Triggered Electrical Stimulation in Patients With Chronic Stroke
Authors: Hong Il Ki , Choi Jong Bae , Lee Jong Ha
Published: July 2012

Background and Purpose—

Paresis of the upper extremity after stroke is not effectively solved by existing therapies. We investigated whether mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic upper extremity in patients with chronic stroke and induced cortical changes.

Methods—

Fourteen subjects with chronic stroke (≥12 months) were randomly allocated to receive mental imagery training combined with electromyogram-triggered electric stimulation (n=7) or generalized functional electric stimulation (n=7) on the forearm extensor muscles of the paretic extremity in 2 20-minute daily sessions 5 days a week for 4 weeks. The upper extremity component of the Fugl-Meyer Motor Assessment, the Motor Activity Log, the modified Barthel Index, and
18
F-fluorodeoxyglucose brain positron emission tomography were measured before and after the intervention.

Results—

The group receiving mental imagery training combined with electromyogram-triggered electric stimulation exhibited significant improvements in the upper extremity component of the Fugl-Meyer Motor Assessment after intervention (median, 7; interquartile range, 5–8;
P
<0.05), but the group receiving functional electric stimulation did not (median, 0; interquartile range, 0–3). Differences in score changes between the 2 groups were significant. The mental imagery training combined with electromyogram-triggered electric stimulation group showed significantly increased metabolism in the contralesional supplementary motor, precentral, and postcentral gyri (
P
uncorrected
<0.001) after the intervention, but the functional electric stimulation group showed no significant differences.

Conclusions—

Mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic extremity in patients with chronic stroke. The intervention increased metabolism in the contralesional motor–sensory cortex.

Clinical Trial Registration—

URL:
https://e-irb.khmccri.or.kr/eirb/receipt/index.html?code=02&status=5
. Unique identifier: KHUHMDIRB 1008-02.
Hangar Talk Survey
Authors: Kearns Suzanne K. , Sutton Jennifer E.
Published: July 2012

Objective:

The current study developed an online hangar talk survey (HTS) to solicit narratives describing challenging scenarios that professional pilots encountered during the hours-building phase of their career.

Background:

The predicted pilot shortage will effectively reduce the minimum flying hours required for pilots to be hired at an airline, resulting in less opportunity to develop nontechnical skills naturalistically. To compensate, threat and error data from the hours-building phase of a pilot’s career are required to inform training development. Pilots often share stories of such experiences, colloquially termed “hangar talk.”

Method:

The HTS gathered 132 narrative descriptions of general aviation (GA) events from pilots along with the event’s impact and whether the pilots would react differently if the scenario were encountered again.

Results:

The distribution of threats reported by GA pilots was similar to that reported at the airline level. Logistic regression analysis revealed that decision-making errors were associated with recognition of the need to react differently in the future, and decision-making errors and proficiency errors were associated with greater perceived impact on skill development.

Conclusion:

The current HTS solicited an array of data similar to the findings of airline-based threat and error observations. Pilots perceive decision-making and proficiency errors as impactful on skill development.

Application:

An HTS can be used to gather naturalistic threat and error data and to create a database of operational stories that can be used to develop nontechnical training based on narrative thought.
The Complex Spine
Authors: Marras William S.
Published: July 2012

Objective:

The aim of this study was to examine the logic behind the knowledge of low-back problem causal pathways.

Background:

Low-back pain and low-back disorders (LBDs) continue to represent the major musculoskeletal risk problem in the workplace, with the prevalence and costs of such disorders increasing over time. In recent years, there has been much criticism of the ability of ergonomics methods to control the risk of LBDs.

Method:

Logical assessment of the systems logic associated with our understanding and prevention of LBDs.

Results:

Current spine loading as well as spine tolerance research efforts are bringing the field to the point where there is a better systems understanding of the inextricable link between the musculoskeletal system and the cognitive system. Loading is influenced by both the physical environment factors as well as mental demands, whereas tolerances are defined by both physical tissue tolerance and biochemically based tissue sensitivities to pain. However, the logic used in many low-back risk assessment tools may be overly simplistic, given what is understood about causal pathways. Current tools typically assess only load or position in a very cursory manner.

Conclusion:

Efforts must work toward satisfying both the physical environment and the cognitive environment for the worker if one is to reliably lower the risk of low-back problems.

Application:

This systems representation of LBD development may serve as a guide to identify gaps in our understanding of LBDs.
A new strategy of carbon fiber reinforced plastic drilling evaluation using thermal measurement
Authors: Park Joung-Man , Kwon Dong-Jun , Wang Zuo-Jia , Gu Ga-Young , DeVries K Lawrence
Published: July 2012

Carbon fiber reinforced plastic composites are being increasingly used for more applications. The evaluation of hole-drilling in these composites remains a difficult and unsolved problem. The drilling process for multi-material composites is quite different than those for their more conventional metal counterparts. In the research reported here, the drilling ability and durability of drills used for drilling carbon fiber reinforced plastic composites, made with a diamond layer was deposited by chemical vapor deposition are evaluated with different r/min. Spindle speed was fixed reasoning based in abundant previous works. A thermal camera and related techniques were used to evaluate chip removal, temperature measurement inside the hole, associated thermal damage during the drilling operation, in an effort to ascertain optimal drilling conditions. Currently, chemical vapor deposition diamond drills appear to produce better holes at lower r/min.