bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep mRNA Sequencing for In Vivo Functional Analysis of Cardiac Transcriptional Regulators
Authors: Matkovich Scot J. , Zhang Yan , Van Booven Derek J. , Dorn Gerald W.
Published: April 2010

Rationale
:

Transcriptional profiling can detect subclinical heart disease and provide insight into disease etiology and functional status. Current microarray-based methods are expensive and subject to artifact.

Objective
:

To develop RNA sequencing methodologies using next generation massively parallel platforms for high throughput comprehensive analysis of individual mouse cardiac transcriptomes. To compare the results of sequencing- and array-based transcriptional profiling in the well-characterized Gαq transgenic mouse hypertrophy/cardiomyopathy model.

Methods and Results
:

The techniques for preparation of individually bar-coded mouse heart RNA libraries for Illumina Genome Analyzer II resequencing are described. RNA sequencing showed that 234 high-abundance transcripts (>60 copies/cell) comprised 55% of total cardiac mRNA. Parallel transcriptional profiling of Gαq transgenic and nontransgenic hearts by Illumina RNA sequencing and Affymetrix Mouse Gene 1.0 ST arrays revealed superior dynamic range for mRNA expression and enhanced specificity for reporting low-abundance transcripts by RNA sequencing. Differential mRNA expression in Gαq and nontransgenic hearts correlated well between microarrays and RNA sequencing for highly abundant transcripts. RNA sequencing was superior to arrays for accurately quantifying lower-abundance genes, which represented the majority of the regulated genes in the Gαq transgenic model.

Conclusions
:

RNA sequencing is rapid, accurate, and sensitive for identifying both abundant and rare cardiac transcripts, and has significant advantages in time- and cost-efficiencies over microarray analysis.
Effects of Free Immunoglobulin Light Chains on Viral Myocarditis
Authors: Matsumori Akira , Shimada Miho , Jie Xiao , Higuchi Hirokazu , Kormelink Tom Groot , Redegeld Frank A.
Published: April 2010

Rationale
:

In recent work, we have demonstrated a crucial role of mast cells in the development of viral myocarditis. Viral infection could lead to increased synthesis of free immunoglobulin light chains (FLC) and our earlier work showed that FLC can trigger mast cell activation.

Objective
:

We studied the possible involvement of FLC in the pathogenesis of viral myocarditis, and therapeutic effects of FLC using an animal model of viral myocarditis.

Methods and Results
:

DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis (EMC) virus. Serum levels and concentrations in the heart of κ FLC on day 14 in mice inoculated with EMC virus were significantly increased compared with controls. Myocardial viral concentration was significantly inhibited, the area of myocardial lesions was smaller in mice treated with κ or λ FLC, and survival of mice given FLC significantly improved. In contrast, an FLC antagonist deteriorated myocarditis. κ and λ FLC chains inhibited EMC viral replication in human amnion cells in vitro. λ FLC significantly increased the gene expression of interleukin-10 in the heart which was previously shown to improve viral myocarditis when given exogenously. FLC also tended to increase the gene expressions of interferon-α and -γ in the heart mice.

Conclusions
:

FLC have antiviral and antiinflammatory effects and improved viral myocarditis in mice. FLC may be promising agents for the treatment of viral myocarditis.
Pregnenolone Sulphate- and Cholesterol-Regulated TRPM3 Channels Coupled to Vascular Smooth Muscle Secretion and Contraction
Authors: Naylor Jacqueline , Li Jing , Milligan Carol J. , Zeng Fanning , Sukumar Piruthivi , Hou Bing , Sedo Alicia , Yuldasheva Nadira , Majeed Yasser , Beri Dhananjay , Jiang Shan , Seymour Victoria A.L. , McKeown Lynn , Kumar Bhaskar , Harteneck Christian , O'Regan David , Wheatcroft Stephen B. , Kearney Mark T. , Jones Clare , Porter Karen E. , Beech David J.
Published: April 2010

Rationale
:

Transient receptor potential melastatin (TRPM)3 is a calcium-permeable ion channel activated by the neurosteroid pregnenolone sulfate and positively coupled to insulin secretion in β cells. Although vascular TRPM3 mRNA has been reported, there is no knowledge of TRPM3 protein or its regulation and function in the cardiovascular system.

Objective
:

To determine the relevance and regulation of TRPM3 in vascular biology.

Methods and Results
:

TRPM3 expression was detected at mRNA and protein levels in contractile and proliferating vascular smooth muscle cells. Calcium entry evoked by pregnenolone sulfate or sphingosine was suppressed by TRPM3 blocking antibody or knock-down of TRPM3 by RNA interference. Low-level constitutive TRPM3 activity was also detected. In proliferating cells, channel activity was coupled negatively to interleukin-6 secretion via a calcium-dependent mechanism. In freshly isolated aorta, TRPM3 positively modulated contractile responses independently of L-type calcium channels. Concentrations of pregnenolone sulfate required to evoke responses were higher than the known plasma concentrations of the steroids, leading to a screen for other stimulators. β-Cyclodextrin was one of few stimulators of TRPM3, revealing the channels to be partially suppressed by endogenous cholesterol, the precursor of pregnenolone. Elevation of cholesterol further suppressed channel activity and loading with cholesterol to generate foam cells precluded observation of TRPM3 activity.

Conclusions
:

The data suggest functional relevance of TRPM3 in contractile and proliferating phenotypes of vascular smooth muscle cells, significance of constitutive channel activity, regulation by cholesterol, and potential value of pregnenolone sulfate in therapeutic vascular modulation.
Enhanced Oligodendrogenesis and Recovery of Neurological Function by Erythropoietin After Neonatal Hypoxic/Ischemic Brain Injury
Authors: Iwai Masanori , Stetler R. Anne , Xing Juan , Hu Xiaoming , Gao Yanqin , Zhang Wenting , Chen Jun , Cao Guodong
Published: April 2010

Background and Purpose—

Neuronal replacement has recently gained attention as a potential therapeutic target under ischemic conditions. However, the oligodendrogenic infrastructure is equally critical for restoration of brain function and is also sensitive to ischemic injury. Erythropoietin (EPO) is a neuroprotective molecule that stimulates neuronal replacement after neonatal hypoxia/ischemia (H/I) when delivered soon after the onset of reperfusion. Because EPO can improve recovery of neurological function in the absence of tissue protection, we hypothesize that EPO may improve neurological function via enhancement of white matter recovery after H/I. Thus, we sought to determine the effects of delayed administration of EPO on white matter injury and recovery of neurological function after neonatal H/I.

Methods—

EPO (1000 U/kg) was injected intraperitoneally at multiple time points beginning 48 hours after H/I in postnatal day 7 rats. The effects of EPO on oligodendrogenesis, white matter injury, and neurogenesis were evaluated using bromodeoxyuridine incorporation and cell-specific immunohistochemistry. Neurological function was assessed by sensorimotor behavioral tests.

Results—

Delayed administration of EPO was incapable of reducing brain volume loss but significantly increased oligodendrogenesis and maturation of oligodendrocytes and attenuated white matter injury after H/I. These effects occurred concurrently with enhanced neurogenesis. Delayed EPO treatment improved behavioral neurological outcomes 14 days after H/I injury.

Conclusions—

Our study demonstrates that delayed administration of EPO promotes oligodendrogenesis and attenuates white matter injury concurrently with increased neurogenesis. These effects likely contribute to the observed improvement in neurological functional outcomes.
Improving the Reliability of Stroke Disability Grading in Clinical Trials and Clinical Practice
Authors: Saver Jeffrey L. , Filip Bogdan , Hamilton Scott , Yanes Anna , Craig Sharon , Cho Michelle , Conwit Robin , Starkman Sidney
Published: April 2010

Background and Purpose—

The modified Rankin Scale rates global disability after stroke and is the most comprehensive and widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability in modified Rankin Scale scoring has been reported. This study sought to develop and validate a short, practicable structured assessment that would enhance interrater reliability.

Methods—

The Rankin Focused Assessment was developed by selecting and refining elements from prior instruments. The Rankin Focused Assessment takes 3 to 5 minutes to apply and provides clear, operationalized criteria to distinguish the 7 assignable global disability levels. The Rankin Focused Assessment was prospectively validated 3 months poststroke among 50 consecutive patients enrolled in the Phase 3 National Institutes of Health Field Administration of Stroke Therapy–Magnesium (FAST-MAG) Trial.

Results—

Among the 50 patients, mean age was 71.5 years (range, 43 to 93 years), 48% were female, and stroke subtype was hemorrhagic in 24%. At Day 90, 43 patients were alive and 7 had died. The modified Rankin Scale median was 2.0 and mean was 2.8. When pairs of 14 raters assessed all enrolled patients, the percent agreement was 94%, the weighted κ was 0.99 (95% CI, 0.99 to 1.0), and the unweighted κ was 0.93 (95% CI, 0.85 to 1.00). Among the 43 surviving patients, the percent agreement was 93%, the weighted κ was 0.99 (0.98 to 1.0), and the unweighted κ was 0.91 (0.82 to 1.00).

Conclusions—

The Rankin Focused Assessment yields high interrater reliability in the grading of final global disability among consecutive patients with stroke participating in a randomized clinical trial. The Rankin Focused Assessment is brief and practical for use in multicenter clinical trials and quality improvement activities.
Key Role of CD36 in Toll-Like Receptor 2 Signaling in Cerebral Ischemia
Authors: Abe Takato , Shimamura Munehisa , Jackman Katherine , Kurinami Hitomi , Anrather Josef , Zhou Ping , Iadecola Costantino
Published: April 2010

Background and Purpose—

Toll-like receptors (TLRs) and the scavenger receptor CD36 are key molecular sensors for the innate immune response to invading pathogens. However, these receptors may also recognize endogenous “danger signals” generated during brain injury, such as cerebral ischemia, and trigger a maladaptive inflammatory reaction. Indeed, CD36 and TLR2 and 4 are involved in the inflammation and related tissue damage caused by brain ischemia. Because CD36 may act as a coreceptor for TLR2 heterodimers (TLR2/1 or TLR2/6), we tested whether such interaction plays a role in ischemic brain injury.

Methods—

The TLR activators FSL-1 (TLR2/6), Pam3 (TLR2/1), or lipopolysaccharide (TLR4) were injected intracerebroventricularly into wild-type or CD36-null mice, and inflammatory gene expression was assessed in the brain. The effect of TLR activators on the infarct produced by transient middle cerebral artery occlusion was also studied.

Results—

The inflammatory response induced by TLR2/1 activation, but not TLR2/6 or TLR4 activation, was suppressed in CD36-null mice. Similarly, TLR2/1 activation failed to increase infarct volume in CD36-null mice, whereas TLR2/6 or TLR4 activation exacerbated postischemic inflammation and increased infarct volume. In contrast, the systemic inflammatory response evoked by TLR2/6 activation, but not by TLR2/1 activation, was suppressed in CD36-null mice.

Conclusions—

In the brain, TLR2/1 signaling requires CD36. The cooperative signaling of TLR2/1 and CD36 is a critical factor in the inflammatory response and tissue damage evoked by cerebral ischemia. Thus, suppression of CD36-TLR2/1 signaling could be a valuable approach to minimize postischemic inflammation and the attendant brain injury.
Efficacy of Intra-Arterial Fibrinolysis for Acute Ischemic Stroke
Authors: Lee Meng , Hong Keun-Sik , Saver Jeffrey L.
Published: April 2010

Background and Purpose—

Although intra-arterial (IA) fibrinolysis for acute ischemic stroke has been clinically available for many years, it is not a therapy approved by the US Food and Drug Administration. Single, randomized, clinical trials (RCTs) have suggested beneficial effects, but no single RCT has demonstrated that IA fibrinolysis yields increases in both good (modified Rankin Scale score 0 to 2) and excellent (modified Rankin Scale score 0 to 1) outcomes when compared with the control group. Relatively few participants and inadequate statistical power in single RCTs may have contributed to this difficulty.

Method—

We performed a systematic literature search to identified RCTs of IA fibrinolysis in acute ischemic stroke. Multiple outcomes were analyzed, with emphasis on good and excellent outcomes at 90 days or at trial end point.

Results—

The systematic search identified 5 RCTs with 395 participants comparing IA fibrinolysis and control. IA fibrinolysis was associated with increased good (odds ratio=2.05; 95% CI, 1.33 to 3.14;
P
=0.001) and excellent (odds ratio=2.14; 95% CI, 1.31 to 3.51;
P
=0.003) outcomes. For additional end points, IA fibrinolysis was associated with increased frequencies of minimal neurologic deficit (National Institutes of Health Stroke Scale score 0 to 1), minimal impairment of activities of daily living (Barthel Index 90 to 100 or 95 to 100), and recanalization. IA fibrinolysis was associated with increased radiological and symptomatic intracerebral hemorrhage. However, there was no difference in mortality between groups.

Conclusions—

Formal meta-analysis suggests that IA fibrinolysis substantially increases recanalization rates and good and excellent clinical outcomes in acute ischemic stroke. Increased hemorrhage frequencies are not associated with any increase in mortality.
Combination of Tissue-Plasminogen Activator With Erythropoietin Induces Blood–Brain Barrier Permeability, Extracellular Matrix Disaggregation, and DNA Fragmentation After Focal Cerebral Ischemia in Mice
Authors: Zechariah Anil , ElAli Ayman , Hermann Dirk M.
Published: April 2010

Background and Purpose—

After 1 clinical study in which recombinant erythropoietin (EPO) protected against ischemic stroke and improved clinical outcome, the German multicenter EPO trial recently reported increased mortality in stroke patients receiving EPO after tissue-plasminogen activator (t-PA)-induced thrombolysis. The reasons for the adverse effects of EPO in t-PA–treated patients are unknown.

Methods—

Mice were submitted to 90 minutes of middle cerebral artery occlusion. Immediately after reperfusion, animals were treated with normal saline or t-PA (10 mg/kg). Animals subsequently received injections of normal saline or EPO that were administered after reperfusion and 12 hours later (2500 IU/kg each). Ischemic injury and brain edema were analyzed at 24 hours after reperfusion by cresyl violet staining and terminal transferase biotinylated-dUTP nick end labeling. Blood–brain barrier integrity was assessed by histochemistry for extravasated serum IgG. Matrix metalloproteinase activity was evaluated by gelatinase zymography.

Results—

EPO did not influence ischemic infarct size but reduced brain swelling. This effect was abolished by t-PA, which exacerbated serum IgG extravasation in ischemic tissue. Gelatinase zymographies revealed that EPO promoted matrix metalloproteinase-9 activity that was markedly elevated by t-PA. Add-on treatment with t-PA increased the density of DNA-fragmented cells in ischemic tissue of EPO-treated, but not vehicle-treated, mice.

Conclusions—

Our data demonstrate a hitherto unknown interaction of t-PA with EPO at the blood–brain interface, ie, promotion of vascular permeability and extracellular matrix breakdown, which may account for the unfavorable actions of EPO in t-PA–treated patients. After t-PA–induced thrombolysis, EPO may not be suitable as stroke treatment.
Intercellular Adhesion Molecule-1 G241R Polymorphism Predicts Risk of Incident Ischemic Stroke
Authors: Volcik Kelly A. , Ballantyne Christie M. , Hoogeveen Ron , Folsom Aaron R. , Boerwinkle Eric
Published: April 2010

Background and Purpose—

Intercellular adhesion molecule-1 levels are increased in pathological studies of atherosclerosis. We evaluated 13 491 participants from the Atherosclerosis Risk in Communities Study to determine the association of intercellular adhesion molecule-1 G241R and K469E polymorphisms with incident coronary heart disease and ischemic stroke.

Methods—

Incidences of ischemic stroke (N=517) and coronary heart disease (N=1629) through 2003 were determined by annual telephone calls and hospital and death certificate surveillance. Risk factors were measured at the baseline examination. Cox proportional-hazards models were used to estimate hazard rate ratios.

Results—

The intercellular adhesion molecule-1 G241
RR
genotype was associated with a significantly increased risk of ischemic stroke in both whites (hazard rate ratio=2.18; 95% CI, 1.01 to 4.68;
P
=0.05) and blacks (hazard rate ratio=7.04; 95% CI, 3.72 to 13.3;
P
<0.001).

Conclusions—

The intercellular adhesion molecule-1 241
RR
genotype is associated with an increased risk of incident ischemic stroke in both whites and blacks.
Is Health-Related Quality of Life Improving After Stroke?
Authors: Edwards Jodi D. , Koehoorn Mieke , Boyd Lara A. , Levy Adrian R.
Published: April 2010

Background and Purpose—

Recent innovations in diagnosis, management, and rehabilitation have resulted in measurable improvements in clinical and functional outcomes after acute stroke. However, whether gains in health-related quality of life after stroke have also occurred is not well characterized. Using 2 Canadian population surveys, the purpose of this study was to identify changes in health-related quality of life in individuals with stroke from 1996 to 2005.

Methods—

Data from the public use files of the National Population Health Survey, Cycle 2 (1996), and the Canadian Community Health Survey, Cycle 3.1. (2005), were used. A total of 847 individuals with stroke were included. Self-reported information on health status based on the Health Utilities Index Mark 3 was used to generate single-attribute and overall health-related quality of life scores. Analysis of covariance and multiple logistic regression were used to determine the relationship between survey year and poststroke impairment adjusting for demographic variables and clinical comorbidities.

Results—

A statistically significant and clinically important reduction in mean overall Health Utilities Index Mark 3 scores was observed for respondents with stroke from 1996 to 2005. In addition, 2 of the 8 single-attribute Health Utilities Index Mark 3 domains showed a significant change between survey years. Significantly more individuals with stroke reported dexterity and cognitive impairment in 2005 compared with respondents in 1996, indicating reduced health-related quality of life for these domains.

Conclusion—

Despite improvements in medical management, quality of life is not improving after stroke in the Canadian population. These findings are useful to generate hypotheses about the impact of advances in management on quality of life after stroke and identify specific domains that may benefit from future study in stroke populations.
Autopsy Findings After Intracranial Thrombectomy for Acute Ischemic Stroke
Authors: Yin Nicole S. , Benavides Sebastian , Starkman Sidney , Liebeskind David S. , Saver Jeffrey A. , Salamon Noriko , Jahan Reza , Duckwiler Gary R. , Tateshima Satoshi , Vinuela Fernando , Vespa Paul M. , Chute Dennis J. , Vinters Harry V.
Published: April 2010

Background and Purpose—

Endovascular thrombectomy is an increasingly used treatment for arterial occlusion in acute stroke. Various devices (including most extensively the Mechanical Embolus Removal in Cerebral Ischemia [MERCI] Retriever device) have been used for this.

Methods—

We review the neuropathologic findings in 5 patients (age range, 59 to 87 years) who died acutely or as late as 38 days after procedures using the MERCI (4 patients) and Penumbra (1 patient) devices were carried out to remove thromboemboli from the middle cerebral artery. Partial recanalization was achieved by thrombectomy in all 5 patients.

Results—

All patients showed extensive cerebral infarcts, 3 of 5 with clinical hemorrhagic transformations of the infarct or frank intraparenchymal hemorrhage after thrombectomy; in 1 case, this was judged to be at least partly on the basis of concomitant hypertensive microvascular disease. With 1 exception, basal arteries examined in detail by immunohistochemistry showed prominent, although usually nonocclusive (and generally nonulcerated), atheromata, often with significant luminal stenosis. One patient showed a subintimal dissection with resultant occlusion of the middle cerebral artery.

Conclusions—

In this highly selected group of patients, the vascular pathological abnormalities affecting basal arteries were variable, but complicated atherosclerosis was a common finding. Extensive irreversible brain necrosis before therapeutic procedures may have contributed to deaths.
Hospitalized Stroke Surveillance in the Community of Durango, Mexico
Authors: Cantu-Brito Carlos , Majersik Jennifer J. , Sánchez Brisa N. , Ruano Angel , Quiñones Gerardo , Arzola José , Morgenstern Lewis B.
Published: April 2010

Background and Purpose—

Vascular conditions are becoming the greatest cause of morbidity and mortality in developing countries. Few studies exist in Latin America. We aimed to perform a rigorous stroke surveillance study in Durango, Mexico.

Methods—

Active and passive surveillance were used to identify all patients with potential stroke presenting to Durango Municipality hospitals from August 2007 to July 2008. Exclusion criteria were subjects younger than 25 years old, stroke attributable to head trauma, and non-Durango Municipality residents. Brain Attack Surveillance in Durango-trained neurologists validated cases as stroke using source documentation. Stroke hospitalization rates were defined to include patients examined in the emergency department or admitted to the hospital.

Results—

Abstractors identified 435 potential cases; 309 (71%) were validated as stroke. Of the validated stroke cases, the median age was 71 and 49% were female. Subtypes were 61.5% ischemic stroke, 20.7% intracerebral hemorrhage, 7.4% subarachnoid hemorrhage, and 10.4% undetermined. Overall initial NIHSS was a median of 11 (interquartile range, 7–17); in-hospital mortality was 39%. When adjusted to the world population, the age-adjusted hospitalization rate of first-ever stroke was 118.2 per 100 000; rates by type were: ischemic stroke, 69.1 (95% CI, 57.5–80.7); intracerebral hemorrhage, 26.7 (95% CI, 19.6–33.8); subarachnoid hemorrhage, 9.5 (95% CI, 5.3–13.8); and unknown, 12.3 (95% CI, 7.4–17.3). Of 190 patients with validated ischemic stroke, 44.2% received lipid testing and 7.4% received carotid imaging and echocardiography; 1.1% received tissue plasminogen activator.

Conclusion—

To our knowledge, this is the first estimate of stroke hospitalization rates in a Mexican community and it provides information important for design of interventions to prevent and treat stroke. This information is critical to reduce Mexico’s stroke burden.
Hyperthyroidism and Risk of Ischemic Stroke in Young Adults
Authors: Sheu Jau-Jiuan , Kang Jiunn-Horng , Lin Hsiu-Chen , Lin Herng-Ching
Published: April 2010

Background and Purpose—

Case reports or case series have reported the association between hyperthyroidism and cerebrovascular disease. However, hyperthyroidism has never been considered as a potential risk factor for stroke in young people. The aim of the present study is to estimate the risk for ischemic stroke among hyperthyroidism patients aged 18 to 44 years during a 5-year period after the diagnosis of hyperthyroidism as compared to a cohort of patients without hyperthyroidism during the same period.

Methods—

A total of 3176 patients with hyperthyroidism were included as the study cohort and 25 408 patients without hyperthyroidism were included as comparison cohort. Each patient was individually tracked for 5 years from their index ambulatory visit to identify those in whom ischemic stroke developed. Cox proportional hazard regressions were performed to compute the 5-year stroke-free survival rate between these 2 cohorts.

Results—

Of the total sample of 28 584 patients, 198 patients (0.7%) had ischemic strokes during the 5-year follow-up period (31 [1.0% of the hyperthyroidism patients] from the study cohort and 167 [0.6% of comparison patients] from the comparison cohort). After adjusting for the patient’s age, gender, income, level of urbanization, hypertension, diabetes, atrial fibrillation, hyperlipidemia, coronary heart disease, and whether they were using antiarrhythmics, the hazard of having ischemic stroke during the 5-year follow-up period was 1.44-times greater (95% CI, 1.02–2.12;
P
=0.038) for patients with hyperthyroidism than for patients in the comparison cohort.

Conclusions—

We conclude that hyperthyroidism is associated with an increased risk for ischemic stroke among young adults.
Intra-Arterial Iodinated Radiographic Contrast Material Injection Administration in a Rat Middle Cerebral Artery Occlusion and Reperfusion Model
Authors: Kurosawa Yuko , Lu Aigang , Khatri Pooja , Carrozzella Janice A. , Clark Joseph F. , Khoury Jane , Tomsick Thomas A.
Published: April 2010

Background and Purpose—

Observations in human interventional stroke treatment led us to hypothesize that iodinated radiographic contrast material use may contribute to intracerebral hemorrhage. Effects of intra-arterial iodinated radiographic contrast material on hemorrhagic transformation after middle cerebral artery occlusion and reperfusion were studied in a placebo-controlled, blinded preclinical study in rats.

Methods—

Four groups of male Sprague-Dawley rats were studied: saline group (n=8), contrast group (n=12), heparin group (n=9), and contrast+heparin group (n=9). The middle cerebral artery was occluded for 5 hours using suture placement. Heparin was infused before suture removal and reperfusion. Saline and/or contrast were infused immediately during reperfusion. Incidence, location, and size of hemorrhage were determined by brain necropsy inspection at 24 hours.

Results—

There was a significant increase in incidence of cortical hemorrhage from control (37.5%), contrast (75.0%), heparin (77.8%) to contrast+heparin (100%; Cochran-Mantel-Haenszel correlation,
P
<0.01). Both pooled contrast groups (85.7%) and pooled heparin groups (88.9%) had higher rates of cortical intracerebral hemorrhage compared with the control group (
P
<0.05). Similar trends for increased cortical intracerebral hemorrhage were seen in the contrast-only (
P
=0.18) and heparin-only (
P
=0.18) groups. There was a trend for decreased infarct edema in rats receiving contrast versus those without (
P
=0.06).

Conclusion—

Intraarterial iodinated radiographic contrast material may increase cortical intracerebral hemorrhage, similar to heparin. Iodinated radiographic contrast material effect may be additive to heparin effect on the incidence of cortical intracerebral hemorrhage.
Preservation of GABAAReceptor Function by PTEN Inhibition Protects Against Neuronal Death in Ischemic Stroke
Authors: Liu Baosong , Li Lijun , Zhang Quanguang , Chang Ning , Wang Dianshi , Shan Yuexin , Li Lei , Wang Hanbin , Feng Hua , Zhang Liang , Brann Darrell W. , Wan Qi
Published: April 2010

Background and Purpose—Downregulation of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), is thought to be a novel neuroprotective strategy in ischemic stroke, but the underlying mechanisms remain unclear. In this study, we aimed to validate the use of PTEN regulation of γ-aminobutyric acid subtype A receptors (GABAARs) as a molecular target for the treatment of ischemic stroke. Because suppression of GABAARs contributes to ischemic neuron death, describing the intracellular signaling that interacts with GABAARs in ischemic neurons would provide a molecular basis for novel stroke therapies.

Methods—We measured surface GABAAR expression by immunocytochemical labeling and surface protein biotinylation assay. Knockdown and overexpression approaches were used to test the effects of PTEN on the expression and function of GABAARs. Neuronal death was detected in both in vitro and in vivo stroke models.

Results—The knockdown and overexpression approaches provided the first evidence that PTEN negatively regulated membrane expression and function of GABAARs in rat hippocampal neurons. Importantly, we demonstrated that a PTEN inhibitor prevented the reduction of surface GABAARs in injured hippocampal neurons subjected to oxygen-glucose deprivation, an in vitro insult that mimics ischemic injury, whereas a GABAAR antagonist significantly reduced this PTEN inhibitor–induced neuroprotection in both the in vitro and in vivo ischemic stroke models.

Conclusions—Our study provides direct evidence that downregulation of PTEN protects against ischemic neuron death by preserving GABAAR function. Targeting this pathway may be an effective strategy for development of selective, potent stroke treatments.
Belgian Fabry Study
Authors: Brouns Raf , Thijs Vincent , Eyskens François , Van den Broeck Marleen , Belachew Shibeshih , Van Broeckhoven Christine , Redondo Patricia , Hemelsoet Dimitri , Fumal Arnaud , Jeangette Sandrine , Verslegers Werner , Baker Robert , Hughes Derralynn , De Deyn Peter Paul
Published: April 2010

Background and Purpose—

Data on the prevalence of Fabry disease in patients with central nervous system pathology are limited and controversial. In this study, we assessed the prevalence of Fabry disease in young patients presenting with cerebrovascular disease in Belgium.

Methods—

In this national, prospective, multicenter study, we screened for Fabry disease in 1000 patients presenting with ischemic stroke, transient ischemic attack, or intracranial hemorrhage; unexplained white matter lesions; or vertebrobasilar dolichoectasia. In male patients, we measured α-galactosidase A (α-GAL A) activity in dried blood spots. Female patients were screened for mutations by exonic DNA sequencing of the α-GAL A gene.

Results—

α-GAL A activity was deficient in 19 men (3.5%), although all had normal α-GAL A gene sequences. Enzymatic deficiency was confirmed on repeat assessment in 2 male patients (0.4%). We identified missense mutations in 8 unrelated female patients (1.8%): Asp313Tyr (n=5), Ala143Thr (n=2), and Ser126Gly (n=1). The pathogenicity of the 2 former missense mutations is controversial. Ser126Gly is a novel mutation that can be linked to late-onset Fabry disease.

Conclusion—

α-GAL A deficiency may play a role in up to 1% of young patients presenting with cerebrovascular disease. These findings suggest that atypical variants of Fabry disease with late-onset cerebrovascular disease exist, although the clinical relevance is unclear in all cases.
Coronary Artery Calcium, Brain Function and Structure
Authors: Vidal Jean-Sébastien , Sigurdsson Sigurdur , Jonsdottir Maria K. , Eiriksdottir Gudny , Thorgeirsson Gudmundur , Kjartansson Olafur , Garcia Melissa E. , van Buchem Mark A. , Harris Tamara B. , Gudnason Vilmundur , Launer Lenore J.
Published: April 2010

Background and Purpose—

Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function.

Methods—

This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function.

Results—

Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes.

Conclusions—

In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology.
The Stingy Hour: How Accounting for Time Affects Volunteering
Authors: DeVoe Sanford E. , Pfeffer Jeffrey
Published: April 2010

These studies examined how the practice of accounting for one’s time—so that work can be billed or charged to specific clients or projects—affects the decision to allocate time to volunteer activities. Using longitudinal data collected from law students transitioning to their first jobs, Study 1 showed that exposure to billing time diminished individuals’ willingness to volunteer, even after controlling for attitudes about volunteering held before entering the workforce as well as the individual’s specific opportunity costs of volunteering time. Studies 2-5 experimentally manipulated billing time and confirmed its causal effect on individuals’ willingness to volunteer and actual volunteering behavior. Study 5 showed that the effect of exposure to billing time on volunteering occurred above and beyond any effects on general self-efficacy or self-determination. Individual differences moderated the effects of billing, such that people who did not value money as much were less affected.
Can’t Control Yourself? Monitor Those Bad Habits
Authors: Quinn Jeffrey M. , Pascoe Anthony , Wood Wendy , Neal David T.
Published: April 2010

What strategies can people use to control unwanted habits? Past work has focused on controlling other kinds of automatic impulses, especially temptations. The nature of habit cuing calls for certain self-control strategies. Because the slow-to-change memory trace of habits is not amenable to change or reinterpretation, successful habit control involves inhibiting the unwanted response when activated in memory. In support, two episode-sampling diary studies demonstrated that bad habits, unlike responses to temptations, were controlled most effectively through spontaneous use of vigilant monitoring (thinking “don’t do it,” watching carefully for slipups). No other strategy was useful in controlling strong habits, despite that stimulus control was effective at inhibiting responses to temptations. A subsequent experiment showed that vigilant monitoring aids habit control, not by changing the strength of the habit memory trace but by heightening inhibitory, cognitive control processes. The implications of these findings for behavior change interventions are discussed.
Information, Perspective, and Judgments About the Self in Face and Dignity Cultures
Authors: Kim Young-Hoon , Cohen Dov
Published: April 2010

People’s judgments about their own moral status and well-being were made differently by those from a Dignity culture (Anglo-Americans) and by those from a Face culture (Asian Americans). Face culture participants were more influenced by information processed from a third-person (compared with first-person) perspective, with information about the self having a powerful effect only when seen through another’s eyes. Thus, (a) Asian Americans felt the greatest need for moral cleansing when thinking about how others would judge their many (vs. few) transgressions, but this effect did not hold when others were not invoked, and (b) Asian Americans defined themselves as having a rich social network and worthwhile life when thinking about how others would evaluate their many (vs. few) friendships, but again, effects did not hold when others were not invoked. In contrast, Anglo-Americans responded to information about their transgressions or friendships, but effects were pronounced only when other people were not invoked.
Reducing the Expression of Implicit Stereotypes: Reflexive Control Through Implementation Intentions
Authors: Mendoza Saaid A. , Gollwitzer Peter M. , Amodio David M.
Published: April 2010

The authors tested the effectiveness of implementation intentions as a strategy for limiting the behavioral expression of implicit stereotypes. Implementation intentions are if-then plans that link an intended response to an anticipated situational cue, thereby enabling a reflexive form of control. The authors examined whether two different types of implementation intentions could improve response accuracy on the Shooter Task, a reaction time measure of implicit stereotyping. In Study 1, participants used a distraction-inhibiting implementation intention designed to engage control over the perception of goal-irrelevant stimuli (e.g., race). In Study 2, participants used a response-facilitating implementation intention designed to promote goal-directed action. Across studies, implementation intentions improved accuracy, thereby limiting the behavioral expression of implicit stereotypes. Furthermore, process dissociation analyses indicated that the distraction-inhibiting implementation intention increased controlled processing while reducing automatic stereotype activation, whereas the response-facilitating implementation intention increased only controlled processing. Implications for goal strategy approaches to reducing prejudice are discussed.
Stigmatizing Materialism: On Stereotypes and Impressions of Materialistic and Experiential Pursuits
Authors: Van Boven Leaf , Campbell Margaret C. , Gilovich Thomas
Published: April 2010

Five studies examined the stigmatization of materialism. Participants expressed negative stereotypes of materialistic people, considering them to be more selfish and self-centered than experiential people (Study 1). Participants also viewed materialistic pursuits as more extrinsically motivated than experiential pursuits (Study 2). These stereotypes led respondents from varied demographic backgrounds to form less favorable impressions of individuals who were associated with prototypically materialistic versus experiential purchases, a result that was statistically mediated by impressions that materialistic purchases were more extrinsically motivated (Study 3). These differential impressions are primarily attributable to the denigration of materialistic people rather than the admiration of experiential people (Study 4). The stigmatization of materialism led participants to like less and enjoy interacting less with their conversation partners when discussing materialistic rather than experiential purchases (Study 5). The authors discuss these findings’ implications for self-perception, accurate social perception, and well-being.
“Think” Versus “Feel” Framing Effects in Persuasion
Authors: Mayer Nicole D. , Tormala Zakary L.
Published: April 2010

Three studies explored think (“I think . . . ”) versus feel (“I feel . . . ”) message framing effects on persuasion.The authors propose a matching hypothesis, suggesting that think framing will be more persuasive when the target attitude or message recipient is cognitively oriented, whereas feel framing will be more persuasive when the target attitude or message recipient is affectively oriented. Study 1 presented cognitively and affectively oriented individuals with a think- or feel-framed message. Study 2 primed cognitive or affective orientation and then presented a think- or feel-framed message. Study 3 presented male and female participants with an advertisement containing think- or feel-framed arguments. Results indicated that think (feel) framing was more persuasive when the target attitude or recipient was cognitively (affectively) oriented. Moreover, Study 2 demonstrated that this matching effect was mediated by processing fluency. Theoretical and practical implications are discussed.
Self-Knowledge Reduces Conflict by Biasing One of Plural Possible Answers
Authors: Nakao Takashi , Mitsumoto Mayo , Nashiwa Hitomi , Takamura Masahiro , Tokunaga Satoko , Miyatani Makoto , Ohira Hideki , Katayama Kaori , Okamoto Akane , Watanabe Yu
Published: April 2010

The authors investigated whether self-knowledge has a function to reduce conflict by biasing one of two choices during occupational choice (e.g., Which occupation do you think you could do better?—dancer or chemist). In the three experiments, event-related brain potentials were recorded. Experiment 1 revealed that the amplitude of the conflict-related negativity (CRN) reflects strength of conflict during occupational choice. Results of Experiment 2 demonstrated that the CRN amplitude during occupational choice was smaller when self-knowledge was activated than when other-knowledge was activated. Experiment 3 showed that the CRN amplitude during occupational choice was decreased more when self-knowledge that biases one choice of occupation was activated than when self-knowledge that does not bias was activated. These results suggest that self-knowledge reduces conflict by biasing one of multiple choices in situations where two or more possible correct answers can be given.
Affective Regulation of Stereotype Activation: It’s the (Accessible) Thought That Counts
Authors: Huntsinger Jeffrey R. , Sinclair Stacey , Dunn Elizabeth , Clore Gerald L.
Published: April 2010

Prior research has found that positive affect, compared to negative affect, increases stereotype activation. In four experiments the authors explore whether the link between affect and stereotype activation depends on the relative accessibility of stereotype-relevant thoughts and response tendencies. As well as manipulating mood, the authors measured or manipulated the accessibility of egalitarian response tendencies (Experiments 1 and 2) and counterstereotypic thoughts (Experiments 2 through 4). In the absence of such response tendencies and thoughts, people in positive moods displayed greater stereotype activation—consistent with past research. By contrast, in the presence of accessible egalitarian response tendencies or counterstereotypic thoughts, people in positive moods exhibited less stereotype activation than those in negative moods. Implications of these results for existing affect—cognition models are discussed.
LMX, Context Perceptions, and Performance: An Uncertainty Management Perspective
Authors: Rosen Christopher C. , Harris Kenneth J. , Kacmar K. Michele
Published: April 2010

This study investigates the role of leader—member exchange in moderating the effects of perceptions of organizational justice and politics on job performance. In contrast to previous research, which has relied on social exchange theory to explain these relationships, the current study uses uncertainty management theory to propose that relationships between employee perceptions of the context (e.g., perceptions of organizational politics, procedural justice, and distributive justice) and performance are stronger for employees who have lower quality leader—member exchange relationships with their supervisors. Analysis of data from a sample of 157 government employees and their supervisors provided partial support for the three hypothesized interactions and indicated that leaders play an important role in determining how employees respond to their perceptions of politics and justice and that neither social exchange theory nor uncertainty management theory fully explained our results. Theoretical and practical implications of our findings as well as directions for future research are provided.
Benevolent Sexism at Work
Authors: King Eden B. , Botsford Whitney , Hebl Michelle R. , Kazama Stephanie , Dawson Jeremy F. , Perkins Andrew
Published: April 2010

The current research draws from ambivalent sexism theory to examine potential gender differences in the quantity and quality of developmental work experiences. In a sample of managers in the energy industry, men and women reported participating in a similar number of developmental experiences (with comparable levels of support), but men rated these experiences as more challenging and received more negative feedback than did women. Similarly, a sample of female managers in the health care industry reported comparable amounts, but less challenging types, of developmental experiences than their male counterparts’. The results of three complementary experiments suggest that benevolent sexism is negatively related to men’s assignment of challenging experiences to female targets but that men and women were equally likely to express interest in challenging experiences. Taken together, these results suggest that stereotype-based beliefs that women should be protected may limit women’s exposure to challenging assignments, which in turn may partially explain the underrepresentation of women at the highest levels of organizations.
Social and psychological adjustment of Chinese Canadian children
Authors: Xinyin Chen  , Tse Hennis Chi-Hang
Published: April 2010

This study examined social and psychological adjustment of immigrant and Canadian-born Chinese children in Canada. Participants included a sample of elementary school children (N = 356, M age = 11 years). Data on social functioning, peer relationships, school-related social competence, perceived self-worth, and loneliness were collected from peer assessments, teacher ratings, and self-reports. The results indicated that immigrant and Canadian-born Chinese children had different experiences of social and psychological adjustment in the school. Among aspects of acculturation, English proficiency and participation in Chinese cultural activities were positively associated with social competence and negatively associated with adjustment problems, particularly in immigrant Chinese children. These results indicate the involvement of contextual factors in children’s social functioning and psychological well-being.
The presence or absence of older siblings and variation in infant goal-directed motor development
Authors: Reid Vincent , Stahl Daniel , Striano Tricia
Published: April 2010

This study investigates the relationship between having an older sibling and early goal-directed motor development. In a longitudinal study, infants were filmed playing with their mother and were observed at 5 and 12 months of age. After each observation, they were assessed with the Mental Bayley Scale. From the mother—child interaction, playing was coded in terms of the production of infant goal-directed actions. Results indicated that infants with siblings produced fewer goal-directed actions at 5 months than infants without older siblings, but at 12 months they produced relatively more goal-directed actions than infants without older siblings. There was no relationship with scores on the Mental Bayley Scale. In order to examine differences in adult behavior that may account for variation in infant motor performance, maternal level of motionese was scored with no differences found between the sibling—no sibling groups.