bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Prevalence of “Ideal Cardiovascular Health” in a Community-Based Population
Authors: Bambs Claudia , Kip Kevin E. , Dinga Andrea , Mulukutla Suresh R. , Aiyer Aryan N. , Reis Steven E. 
Published: February 2011

Background—
Cardiovascular health is a new construct defined by the American Heart Association (AHA) as part of its 2020 Impact Goal definition. The applicability of this construct to community-based populations and the distributions of its components by race and sex have not been reported.

Methods and Results—

The AHA construct of cardiovascular health and the AHA ideal health behaviors index and ideal health factors index were evaluated among 1933 participants (mean age 59 years; 44% blacks; 66% women) in the community-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. One of 1933 participants (0.1%) met all 7 components of the AHA's definition of ideal cardiovascular health. Less than 10% of participants met ≥5 components of ideal cardiovascular health in all subgroups (by race, sex, age, and income level). Thirty-nine subjects (2.0%) had all 4 components of the ideal health behaviors index and 27 (1.4%) had all 3 components of the ideal health factors index. Blacks had significantly fewer ideal cardiovascular health components than whites (2.0±1.2 versus 2.6±1.4;
P
<0.001). After adjustment by sex, age, and income level, blacks had 82% lower odds of having ≥5 components of ideal cardiovascular health (odds ratio 0.18, 95% confidence interval, 0.10 to 0.34;
P
<0.001). No interaction was found between race and sex.

Conclusion—
The prevalence of ideal cardiovascular health is extremely low in a middle-aged community-based study population. Comprehensive individual and population-based interventions must be developed to support the attainment of the AHA′s 2020 Impact Goal for cardiovascular health.
Outcome of Patients With Low-Gradient “Severe” Aortic Stenosis and Preserved Ejection Fraction
Authors: Jander Nikolaus , Minners Jan , Holme Ingar , Gerdts Eva , Boman Kurt , Brudi Philippe , Chambers John B. , Egstrup Kenneth , Kesäniemi Y. Antero , Malbecq William , Nienaber Christoph A. , Ray Simon , Rossebø Anne , Pedersen Terje R. , Skjærpe Terje , Willenheimer Ronnie , Wachtell Kristian , Neumann Franz-Josef , Gohlke-Bärwolf Christa 
Published: February 2011

Background—

Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area <1.0 cm
2
and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient “severe” stenosis (defined as aortic valve area <1.0 cm
2
and mean gradient ≤40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.

Methods and Results—

Outcome in patients with low-gradient “severe” aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm
2
; mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67±10 years; ejection fraction, ≥55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182±64 versus 212±68 g;
P
<0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (
P
=0.37; major cardiovascular events, 50.9% versus 48.5%,
P
=0.58; cardiovascular death, 7.8% versus 4.9%,
P
=0.19). Low-gradient severe stenosis patients with reduced stroke volume index (≤35 mL/m
2
; n=223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%;
P
=0.53).

Conclusions—
Patients with low-gradient “severe” aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis.
Amount but Not Pattern of Protective Sensory Stimulation Alters Recovery After Permanent Middle Cerebral Artery Occlusion
Authors: Davis Melissa F. , Lay Christopher C. , Chen-Bee Cynthia H. , Frostig Ron D. 
Published: February 2011

Background and Purpose—
Using a rodent model of ischemia (permanent middle cerebral artery occlusion), our laboratory previously demonstrated that 4.27 minutes of patterned single-whisker stimulation delivered over 120 minutes can fully protect from impending damage when initiated within 2 hours of permanent middle cerebral artery occlusion (“early”). When initiated 3 hours postpermanent middle cerebral artery occlusion (“late”), stimulation resulted in irreversible damage. Here we investigate the effect of altering pattern, distribution, or amount of stimulation in this model.

Methods—
We assessed the cortex using functional imaging and histological analysis with altered stimulation treatment protocols. In 2 groups of animals we administered the same number of whisker deflections but in a random rather than patterned fashion distributed either over 120 minutes or condensed into 10 minutes postpermanent middle cerebral artery occlusion. We also tested increased (full-whisker array versus single-whisker) stimulation.

Results—
Early random whisker stimulation (condensed or dispersed) resulted in protection equivalent to early patterned stimulation. Early full-whisker array patterned stimulation also resulted in complete protection but promoted faster recovery. Late full-whisker array patterned stimulation, however, resulted in loss of evoked function and infarct volumes larger than those sustained by single-whisker counterparts.

Conclusions—
When induced early on after ischemic insult, stimulus-evoked cortical activity, irrespective of the parameters of peripheral stimulation that induced it, seems to be the important variable for neuroprotection.
Interrater Reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a Multicenter Study
Authors: Ichord Rebecca N. , Bastian Rachel , Abraham Lisa , Askalan Rand , Benedict Susan , Bernard Timothy J. , Beslow Lauren , deVeber Gabrielle , Dowling Michael , Friedman Neil , Fullerton Heather , Jordan Lori , Kan Li , Kirton Adam , Amlie-Lefond Catherine , Licht Daniel , Lo Warren , McClure Chalmer , Pavlakis Steve , Smith Sabrina E. , Tan Marilyn , Kasner Scott , Jawad Abbas F. 
Published: February 2011

Background and Purpose—
Stroke is an important cause of death and disability among children. Clinical trials for childhood stroke require a valid and reliable acute clinical stroke scale. We evaluated interrater reliability (IRR) of a pediatric adaptation of the National Institutes of Health Stroke Scale.

Methods—
The pediatric adaptation of the National Institutes of Health Stroke Scale was developed by pediatric and adult stroke experts by modifying each item of the adult National Institutes of Health Stroke Scale for children, retaining all examination items and scoring ranges of the National Institutes of Health Stroke Scale. Children 2 to 18 years of age with acute arterial ischemic stroke were enrolled in a prospective cohort study from 15 North American sites from January 2007 to October 2009. Examiners were child neurologists certified in the adult National Institutes of Health Stroke Scale. Each subject was examined daily for 7 days or until discharge. A subset of patients at 3 sites was scored simultaneously and independently by 2 study neurologists.

Results—
IRR testing was performed in 25 of 113 a median of 3 days (interquartile range, 2 to 4 days) after symptom onset. Patient demographics, total initial pediatric adaptation of the National Institutes of Health Stroke Scale scores, risk factors, and infarct characteristics in the IRR subset were similar to the non-IRR subset. The 2 raters' total scores were identical in 60% and within 1 point in 84%. IRR was excellent as measured by concordance correlation coefficient of 0.97 (95% CI, 0.94 to 0.99); intraclass correlation coefficient of 0.99 (95% CI, 0.97 to 0.99); precision measured by Pearson ρ of 0.97; and accuracy measured by the bias correction factor of 1.0.

Conclusions—
There was excellent IRR of the pediatric adaptation of the National Institutes of Health Stroke Scale in a multicenter prospective cohort performed by trained child neurologists.
Endothelial Nitric Oxide Synthase Mediates Endogenous Protection Against Subarachnoid Hemorrhage-Induced Cerebral Vasospasm
Authors: Vellimana Ananth K. , Milner Eric , Azad Tej D. , Harries Michael D. , Zhou Meng-Liang , Gidday Jeffrey M. , Han Byung Hee , Zipfel Gregory J. 
Published: February 2011

Background and Purpose—
Vasospasm-induced delayed cerebral ischemia remains a major source of morbidity in patients with aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that activating innate neurovascular protective mechanisms by preconditioning (PC) may represent a novel therapeutic approach against SAH-induced vasospasm and neurological deficits and, secondarily, that the neurovascular protection it provides is mediated by endothelial nitric oxide synthase (eNOS).

Methods—
Wild-type mice were subjected to hypoxic PC or normoxia followed 24 hours later by SAH. Neurological function was analyzed daily; vasospasm was assessed on post-surgery Day 2. Nitric oxide availability, eNOS expression, and eNOS activity were also assessed. In a separate experiment, wild-type and eNOS-null mice were subjected to hypoxic PC or normoxia followed by SAH and assessed for vasospasm and neurological deficits.

Results—

PC nearly completely prevented SAH-induced vasospasm and neurological deficits. It also prevented SAH-induced reduction in nitric oxide availability and increased eNOS activity in mice with and without SAH. PC-induced protection against vasospasm and neurological deficits was lost in wild-type mice treated with the nitric oxide synthase inhibitor
N
G
-nitro-
l
-arginine methyl ester and in eNOS-null mice.

Conclusions—
Endogenous protective mechanisms against vasospasm exist, are powerful, and can be induced by PC. eNOS-derived nitric oxide is a critical mediator of PC-induced neurovascular protection. These data provide strong “proof-of-principle” evidence that PC represents a promising new strategy to reduce vasospasm and delayed cerebral ischemia after SAH.
Looming Auditory Collision Warnings for Driving
Authors: Gray Rob 
Published: February 2011

Objective: A driving simulator was used to compare the effectiveness of increasing intensity (looming) auditory warning signals with other types of auditory warnings. Background: Auditory warnings have been shown to speed driver reaction time in rear-end collision situations; however, it is not clear which type of signal is the most effective. Although verbal and symbolic (e.g., a car horn) warnings have faster response times than abstract warnings, they often lead to more response errors. Method: Participants ( N = 20) experienced four nonlooming auditory warnings (constant intensity, pulsed, ramped, and car horn), three looming auditory warnings (“veridical,” “early,” and “late”), and a no-warning condition. In 80% of the trials, warnings were activated when a critical response was required, and in 20% of the trials, the warnings were false alarms. For the early (late) looming warnings, the rate of change of intensity signaled a time to collision ( TTC) that was shorter (longer) than the actual TTC. Results: Veridical looming and car horn warnings had significantly faster brake reaction times (BRT) compared with the other nonlooming warnings (by 80 to 160 ms). However, the number of braking responses in false alarm conditions was significantly greater for the car horn. BRT increased significantly and systematically as the TTC signaled by the looming warning was changed from early to veridical to late. Conclusion: Looming auditory warnings produce the best combination of response speed and accuracy. Application: The results indicate that looming auditory warnings can be used to effectively warn a driver about an impending collision.
An elevated level of BNP in plasma is related to the development of good collateral circulation in coronary artery disease
Authors: Xi Wei-Wei , Cheng Gang , Lv Shumin , Gao Qinqin , Bu Gang , Zhou Ying , Xu Geng 
Published: February 2011

Objective: B-type natriuretic peptide (BNP) was recently demonstrated to be a potential stimulator of angiogenesis and arteriogenesis. The correlation between BNP level and collateral formation in patients with coronary artery disease (CAD) has not been reported. Methods and results: The study included 311 consecutive patients who underwent coronary angiography were divided into three groups according to coronary angiography and collateral formation: normal group (100 patients with normal coronary angiographic findings); poor collateral group (116 patients with at least one coronary stenosis of ≥75% without visible collateral circulation); and good collateral group (95 patients with at least one coronary stenosis of ≥75% with well-developed collateral circulation). Collateral score was analyzed using the Cohen–Rentrop classification. Plasma BNP levels were 45.77 ± 4.66 pg/ml, 116.40 ± 28.15 pg/ml, and 254.20 ± 42.85 pg/ml for patients in normal, poor collateral, and good collateral groups, respectively. Plasma BNP levels in the latter were significantly higher than in the normal group ( p < 0.01) and poor collateral group ( p < 0.05). There were no significant differences between the good collateral group and poor collateral group when compared with left ventricular ejection fraction (LVEF), left ventricular dimensions at end diastole (LVEDd), age, severity of angiographic disease, and other cardiovascular risk factors. After adjustment in the multiple ordinal logistic regression model, plasma BNP levels showed a strong independent association with collateral Cohen–Rentrop score (χ2 = 5.636, OR = 1.002, 95% CI 1.000–1.004, p = 0.018). Conclusions: An elevated level of BNP in plasma is independently associated with collateral development; patients with good collaterals tend to have a higher BNP level.
Lenalidomide targets clonogenic side population in multiple myeloma: pathophysiologic and clinical implications
Authors: Jakubikova Jana , Adamia Sophia , Kost-Alimova Maria , Klippel Steffen , Cervi David , Daley John F. , Cholujova Dana , Kong Sun-Young , Leiba Merav , Blotta Simona , Ooi Melissa , Delmore Jake , Laubach Jacob , Richardson Paul G. , Sedlak Jan , Anderson Kenneth C. , Mitsiades Constantine S. 
Published: February 2011

Abstract
Recurrence of multiple myeloma (MM) after therapy suggests the presence of tumor-initiating subpopulations. In our study, we performed flow cytometry–based Hoechst 33342 staining to evaluate the existence of a MM population with stem-like features known as side population (SP) cells. SP cells exhibit substantial heterogeneity in MM cell lines and primary MM cells; express CD138 antigen in MM cell lines; display higher mRNA expression and functional activity of ABCG2 transporter; and have a higher proliferation index compared with non-SP cells. We observed evidence for clonogenic potential of SP cells, as well as the ability of SP cells to regenerate original population. Moreover, SP cells revealed higher tumorigenicity compared with non-SP cells. Importantly, lenalidomide decreased the percentage and clonogenicity of SP cells, and also induced phosphorylation changes in Akt, GSK-3α/β, MEK1, c-Jun, p53, and p70S6K in SP cells. Adherence to bone marrow stromal cells (BMSCs) increased the percentage, viability, and proliferation potential of SP cells. Lenalidomide and thalidomide abrogated this stimulatory effect of BMSCs and significantly decreased the percentage of SP cells. Our studies demonstrate a novel mechanism of action for lenalidomide, namely targeting SP fraction, providing the framework for new therapeutic strategies targeting subpopulations of MM cells including presumptive stem cells.
An embryonic stage–specific enhancer within the murine β-globin locus mediates domain-wide histone hyperacetylation
Authors: Fromm George , Cadiz-Rivera Brenda , de Vries Christina , Getman Michael , McGrath Kathleen E. , Kingsley Paul D. , Fields Jennifer , Fiering Steven , Bulger Michael 
Published: February 2011

Abstract
In mammalian nuclei, a select number of tissue-specific gene loci exhibit broadly distributed patterns of histone modifications, such as histone hyperacetylation, that are normally associated with active gene promoters. Previously, we characterized such hyperacetylated domains within mammalian β-globin gene loci, and determined that within the murine locus, neither the β-globin locus control region nor the gene promoters were required for domain formation. Here, we identify a developmentally specific erythroid enhancer, hypersensitive site-embryonic 1 (HS-E1), located within the embryonic β-globin domain in mouse, which is homologous to a region located downstream of the human embryonic ϵ-globin gene. This sequence exhibits nuclease hypersensitivity in primitive erythroid cells and acts as an enhancer in gain-of-function assays. Deletion of HS-E1 from the endogenous murine β-globin locus results in significant decrease in the expression of the embryonic β-globin genes and loss of the domain-wide pattern of histone hyperacetylation. The data suggest that HS-E1 is an enhancer that is uniquely required for β-like globin expression in primitive erythroid cells, and that it defines a novel class of enhancer that works in part by domain-wide modulation of chromatin structure.
PrPSc spreading patterns in the brain of sheep linked to different prion types
Authors: Wemheuer Wiebke M , Benestad Sylvie L , Wrede Arne , Wemheuer Wilhelm E , Brenig Bertram , Bratberg Bjørn , Schulz-Schaeffer Walter J 
Published: February 2011

Abstract
Scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (BSE) and Creutzfeldt-Jakob disease in humans. According to the prion hypothesis, the pathological isoform (PrPSc) of the cellular prion protein (PrPc) comprises the essential, if not exclusive, component of the transmissible agent. Currently, two types of scrapie disease are known - classical and atypical/Nor98 scrapie. In the present study we examine 24 cases of classical and 25 cases of atypical/Nor98 scrapie with the sensitive PET blot method and validate the results with conventional immunohistochemistry. The sequential detection of PrPSc aggregates in the CNS of classical scrapie sheep implies that after neuroinvasion a spread from spinal cord and obex to the cerebellum, diencephalon and frontal cortex via the rostral brainstem takes place. We categorize the spread of PrPSc into four stages: the CNS entry stage, the brainstem stage, the cruciate sulcus stage and finally the basal ganglia stage. Such a sequential development of PrPSc was not detectable upon analysis of the present atypical/Nor98 scrapie cases. PrPSc distribution in one case of atypical/Nor98 scrapie in a presumably early disease phase suggests that the spread of PrPSc aggregates starts in the di- or telencephalon. In addition to the spontaneous generation of PrPSc, an uptake of the infectious agent into the brain, that bypasses the brainstem and starts its accumulation in the thalamus, needs to be taken into consideration for atypical/Nor98 scrapie.
Staphylococcus aureus seroproteomes discriminate ruminant isolates causing mild or severe mastitis
Authors: Le Maréchal Caroline , Jardin Julien , Jan Gwenaël , Even Sergine , Pulido Coralie , Guibert Jean-Michel , Hernandez David , François Patrice , Schrenzel Jacques , Demon Dieter , Meyer Evelyne , Berkova Nadia , Thiéry Richard , Vautor Eric , Le Loir Yves 
Published: February 2011

Abstract

Staphylococcus aureus is a major cause of mastitis in ruminants. In ewe mastitis, symptoms range from subclinical to gangrenous mastitis. S. aureus factors or host-factors contributing to the different outcomes are not completely elucidated. In this study, experimental mastitis was induced on primiparous ewes using two S. aureus strains, isolated from gangrenous (strain O11) or subclinical (strain O46) mastitis. Strains induced drastically distinct clinical symptoms when tested in ewe and mice experimental mastitis. Notably, they reproduced mild (O46) or severe (O11) mastitis in ewes. Ewe sera were used to identify staphylococcal immunoreactive proteins commonly or differentially produced during infections of variable severity and to define core and accessory seroproteomes. Such SERological Proteome Analysis (SERPA) allowed the identification of 89 immunoreactive proteins, of which only 52 (58.4%) were previously identified as immunogenic proteins in other staphylococcal infections. Among the 89 proteins identified, 74 appear to constitute the core seroproteome. Among the 15 remaining proteins defining the accessory seroproteome, 12 were specific for strain O11, 3 were specific for O46. Distribution of one protein specific for each mastitis severity was investigated in ten other strains isolated from subclinical or clinical mastitis. We report here for the first time the identification of staphylococcal immunogenic proteins common or specific to S. aureus strains responsible for mild or severe mastitis. These findings open avenues in S. aureus mastitis studies as some of these proteins, expressed in vivo, are likely to account for the success of S. aureus as a pathogen of the ruminant mammary gland.
Cellular stress-induced up-regulation of FMRP promotes cell survival by modulating PI3K-Akt phosphorylation cascades
Authors: Jeon Se Jin , Seo Jung Eun , Yang Sung-Il , Choi Ji Woong , Wells David , Shin Chan Young , Ko Kwang Ho 
Published: February 2011

Abstract

Background
Fragile X syndrome (FXS), the most commonly inherited mental retardation and single gene cause of autistic spectrum disorder, occurs when the Fmr1 gene is mutated. The product of Fmr1, fragile X linked mental retardation protein (FMRP) is widely expressed in HeLa cells, however the roles of FMRP within HeLa cells were not elucidated, yet. Interacting with a diverse range of mRNAs related to cellular survival regulatory signals, understanding the functions of FMRP in cellular context would provide better insights into the role of this interesting protein in FXS. Using HeLa cells treated with etoposide as a model, we tried to determine whether FMRP could play a role in cell survival.

Methods
Apoptotic cell death was induced by etoposide treatment on Hela cells. After we transiently modulated FMRP expression (silencing or enhancing) by using molecular biotechnological methods such as small hairpin RNA virus-induced knock down and overexpression using transfection with FMRP expression vectors, cellular viability was measured using propidium iodide staining, TUNEL staining, and FACS analysis along with the level of activation of PI3K-Akt pathway by Western blot. Expression level of FMRP and apoptotic regulator BcL-xL was analyzed by Western blot, RT-PCR and immunocytochemistry.

Results
An increased FMRP expression was measured in etoposide-treated HeLa cells, which was induced by PI3K-Akt activation. Without FMRP expression, cellular defence mechanism via PI3K-Akt-Bcl-xL was weakened and resulted in an augmented cell death by etoposide. In addition, FMRP over-expression lead to the activation of PI3K-Akt signalling pathway as well as increased FMRP and BcL-xL expression, which culminates with the increased cell survival in etoposide-treated HeLa cells.

Conclusions
Taken together, these results suggest that FMRP expression is an essential part of cellular survival mechanisms through the modulation of PI3K, Akt, and Bcl-xL signal pathways.