bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of ATF3 Gene Network by Triglyceride-Rich Lipoprotein Lipolysis Products Increases Vascular Apoptosis and Inflammation
Authors: Aung Hnin H. , Lame Michael W. , Gohil Kishorchandra , An Chung-Il , Wilson Dennis W. , Rutledge John C. 
Published: July 2013

Objective—
Elevation of triglyceride-rich lipoproteins (TGRLs) contributes to the risk of atherosclerotic cardiovascular disease. Our work has shown that TGRL lipolysis products in high physiological to pathophysiological concentrations cause endothelial cell injury; however, the mechanisms remain to be delineated.

Approach and Results—

We analyzed the transcriptional signaling networks in arterial endothelial cells exposed to TGRL lipolysis products. When human aortic endothelial cells in culture were exposed to TGRL lipolysis products, activating transcription factor 3 (ATF3) was identified as a principal response gene. Induction of ATF3 mRNA and protein was confirmed by quantitative reverse-transcription polymerase chain reaction and Western blot respectively. Immunofluorescence analysis showed that ATF3 accumulated in the nuclei of cells treated with lipolysis products. Nuclear expression of phosphorylated c-Jun N-terminal kinase (JNK), previously shown to be an initiator of the ATF3 signaling cascade, also was demonstrated. Small interfering RNA (siRNA)–mediated inhibition of ATF3 blocked lipolysis products–induced transcription of E-selectin and interleukin-8, but not interleukin-6 or nuclear factor-κB. c-Jun, a downstream protein in the JNK pathway, was phosphorylated, whereas expression of nuclear factor-κB–dependent JunB was downregulated. Additionally, JNK siRNA suppressed ATF3 and p-c-Jun protein expression, suggesting that JNK is upstream of the ATF3 signaling pathway. In vivo studies demonstrated that infusion of TGRL lipolysis products into wild-type mice induced nuclear ATF3 accumulation in carotid artery endothelium. ATF3
−/−
mice were resistant to vascular apoptosis precipitated by treatment with TGRL lipolysis products. Also peripheral blood monocytes isolated from postprandial humans had increased ATF3 expression as compared with fasting monocytes.

Conclusions—
This study demonstrates that TGRL lipolysis products activate ATF3-JNK transcription factor networks and induce endothelial cells inflammatory response.
Cardioprotective Effects of Exenatide in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Woo Jong Shin , Kim Weon , Ha Sang Jin , Kim Jin Bae , Kim Soo-Joong , Kim Woo-Shik , Seon Hyun Ju , Kim Kwon Sam 
Published: July 2013

Objective—
Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment–elevation myocardial infarction.

Approach and Results—

Fifty-eight patients with ST-segment–elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g;
P
<0.01). At 6 months, the exenatide group showed a significantly lower value of
E
/
E
′ with improved strain parameters. No significant adverse effects of exenatide administration were detected.

Conclusions—
In patients with ST-segment–elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.
Aortic Remodeling After Transverse Aortic Constriction in Mice Is Attenuated With AT
1
Receptor Blockade
Authors: Kuang Shao-Qing , Geng Liang , Prakash Siddharth K. , Cao Jiu-Mei , Guo Steven , Villamizar Carlos , Kwartler Callie S. , Peters Andrew M. , Brasier Allan R. , Milewicz Dianna M. 
Published: July 2013

Objective—
Although hypertension is the most common risk factor for thoracic aortic diseases, it is not understood how increased pressures on the ascending aorta lead to aortic aneurysms. We investigated the role of angiotensin II type 1 receptor activation in ascending aortic remodeling in response to increased biomechanical forces using a transverse aortic constriction (TAC) mouse model.

Approach and Results—

Two weeks after TAC, the increased biomechanical pressures led to ascending aortic dilatation and thickening of the medial and adventitial layers of the aorta. There was significant adventitial hyperplasia and inflammatory responses in TAC ascending aortas were accompanied by increased adventitial collagen, elevated inflammatory and proliferative markers, and increased cell density attributable to accumulation of myofibroblasts and macrophages. Treatment with losartan significantly blocked TAC-induced vascular inflammation and macrophage accumulation. However, losartan only partially prevented TAC-induced adventitial hyperplasia, collagen accumulation, and ascending aortic dilatation. Increased
Tgfb2
expression and phosphorylated-Smad2 staining in the medial layer of TAC ascending aortas were effectively blocked with losartan. In contrast, the increased
Tgfb1
expression and adventitial phospho-Smad2 staining were only partially attenuated by losartan. In addition, losartan significantly blocked extracellular signal–regulated kinase activation and reactive oxygen species production in the TAC ascending aorta.

Conclusions—
Inhibition of the angiotensin II type 1 receptor using losartan significantly attenuated the vascular remodeling associated with TAC but did not completely block the increased transforming growth factor-β1 expression, adventitial Smad2 signaling, and collagen accumulation. These results help to delineate the aortic transforming growth factor-β signaling that is dependent and independent of the angiotensin II type 1 receptor after TAC.
Toll-Like Receptor 2/6 Agonist Macrophage-Activating Lipopeptide-2 Promotes Reendothelialization and Inhibits Neointima Formation After Vascular Injury
Authors: Grote Karsten , Sonnenschein Kristina , Kapopara Piyushkumar R. , Hillmer Anja , Grothusen Christina , Salguero Gustavo , Kotlarz Daniel , Schuett Harald , Bavendiek Udo , Schieffer Bernhard 
Published: July 2013

Objective—
Reendothelialization after vascular injury (ie, balloon angioplasty or stent implantation) is clinically extremely relevant to promote vascular healing. We here investigated the therapeutic potential of the toll-like receptor 2/6 agonist macrophage-activating lipopeptide (MALP)-2 on reendothelialization and neointima formation in a murine model of vascular injury.

Approach and Results—

The left common carotid artery was electrically injured, and reendothelialization was quantified by Evans blue staining after 3 days. A single injection of MALP-2 (1 or 10 µg, IV) after vascular injury accelerated reendothelialization (
P
<0.001). Proliferation of endothelial cells at the wound margins determined by 5-ethynyl-2′-deoxyuridine incorporation was significantly higher in MALP-2–treated animals (
P
<0.05). Furthermore, wire injury–induced neointima formation of the left common carotid artery was completely prevented by a single injection of MALP-2 (10 µg, IV). In vitro, MALP-2 induced proliferation (BrdU incorporation) and closure of an artificial wound of endothelial cells (
P
<0.05) but not of smooth muscle cells. Protein array and ELISA analysis of isolated primary endothelial cells and ex vivo stimulated carotid segments revealed that MALP-2 stimulated the release of multiple growth factors and cytokines predominantly from endothelial cells. MALP-2 induced a strong activation of the mitogen-activated protein kinase cascade in endothelial cells, which was attenuated in smooth muscle cells. Furthermore, MALP-2 significantly enhanced circulating monocytes and hematopoietic progenitor cells.

Conclusions—
The toll-like receptor 2/6 agonist MALP-2 promotes reendothelialization and inhibits neointima formation after experimental vascular injury via enhanced proliferation and migration of endothelial cells. Thus, MALP-2 represents a novel therapeutic option to accelerate reendothelialization after vascular injury.
Prospective Randomized Study to Assess the Efficacy of Site and Rate of Atrial Pacing on Long-Term Progression of Atrial Fibrillation in Sick Sinus Syndrome
Authors: Lau Chu-Pak , Tachapong Ngarmukos , Wang Chun-Chieh , Wang Jing-feng , Abe Haruhiko , Kong Chi-Woon , Liew Reginald , Shin Dong-Gu , Padeletti Luigi , Kim You-Ho , Omar Razali , Jirarojanakorn Kreingkrai , Kim Yoon-Nyun , Chen Mien-Cheng , Sriratanasathavorn Charn , Munawar Muhammad , Kam Ruth , Chen Jan-Yow , Cho Yong-Keun , Li Yi-Gang , Wu Shu-Lin , Bailleul Christophe , Tse Hung-Fat 
Published: July 2013

Background—
Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF.

Methods and Results—

We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79–1.75;
P
=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79–1.74;
P
=0.69) did not prevent the development of persistent AF.

Conclusions—
In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00419640.
In-Hospital Risk Prediction for Post-stroke Depression
Authors: de Man-van Ginkel Janneke M. , Hafsteinsdóttir Thóra B. , Lindeman Eline , Ettema Roelof G.A. , Grobbee Diederick E. , Schuurmans Marieke J. 
Published: July 2013

Background and Purpose—
The timely detection of post-stroke depression is complicated by a decreasing length of hospital stay. Therefore, the Post-stroke Depression Prediction Scale was developed and validated. The Post-stroke Depression Prediction Scale is a clinical prediction model for the early identification of stroke patients at increased risk for post-stroke depression.

Methods—
The study included 410 consecutive stroke patients who were able to communicate adequately. Predictors were collected within the first week after stroke. Between 6 to 8 weeks after stroke, major depressive disorder was diagnosed using the Composite International Diagnostic Interview. Multivariable logistic regression models were fitted. A bootstrap-backward selection process resulted in a reduced model. Performance of the model was expressed by discrimination, calibration, and accuracy.

Results—

The model included a medical history of depression or other psychiatric disorders, hypertension, angina pectoris, and the Barthel Index item dressing. The model had acceptable discrimination, based on an area under the receiver operating characteristic curve of 0.78 (0.72–0.85), and calibration (
P
value of the
U-
statistic, 0.96). Transforming the model to an easy-to-use risk-assessment table, the lowest risk category (sum score, <−10) showed a 2% risk of depression, which increased to 82% in the highest category (sum score, >21).

Conclusions—
The clinical prediction model enables clinicians to estimate the degree of the depression risk for an individual patient within the first week after stroke.
Physical Activity Frequency and Risk of Incident Stroke in a National US Study of Blacks and Whites
Authors: McDonnell Michelle N. , Hillier Susan L. , Hooker Steven P. , Le Anh , Judd Suzanne E. , Howard Virginia J. 
Published: July 2013

Background and Purpose—
Regular physical activity (PA) is an important recommendation for stroke prevention. We compared the associations of self-reported PA with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Methods—
REGARDS recruited 30 239 US blacks (42%) and whites, aged ≥45 years with follow-up every 6 months for stroke events. Excluding those with prior stroke, analysis involved 27 348 participants who reported their frequency of moderate to vigorous intensity PA at baseline according to 3 categories: none (physical inactivity), 1 to 3×, and ≥4× per week. Stroke and transient ischemic attack cases were identified during an average of 5.7 years of follow-up. Cox proportional hazards models were constructed to examine whether self-reported PA was associated with risk of incident stroke.

Results—

Physical inactivity was reported by 33% of participants and was associated with a hazard ratio of 1.20 (95% confidence intervals, 1.02–1.42;
P
=0.035). Adjustment for demographic and socioeconomic factors did not affect hazard ratio, but further adjustment for traditional stroke risk factors (diabetes mellitus, hypertension, body mass index, alcohol use, and smoking) partially attenuated this risk (hazard ratio, 1.14 [0.95–1.37];
P
=0.17). There was no significant association between PA frequency and risk of stroke by sex groups, although there was a trend toward increased risk for men reporting PA 0 to 3× a week compared with ≥4× a week.

Conclusions—
Self-reported low PA frequency is associated with increased risk of incident stroke. Any effect of PA is likely to be mediated through reducing traditional risk factors.
Natural History of Unruptured Intracranial Aneurysms
Authors: Juvela Seppo , Poussa Kristiina , Lehto Hanna , Porras Matti 
Published: July 2013

Background and Purpose—
Unruptured intracranial aneurysms are increasingly being detected and are a notable healthcare burden. We investigated the long-term natural history of unruptured intracranial aneurysms and risk factors predictive of subsequent rupture.

Methods—
A total of 142 patients with 181 unruptured intracranial aneurysms diagnosed between 1956 and 1978, when these were not treated, were followed up until death or subarachnoid hemorrhage, or until 2011 to 2012. Annual and cumulative incidences of aneurysm rupture and risk factors for rupture were studied using Kaplan–Meier survival analysis and Cox proportional hazards regression models.

Results—

The median follow-up time was 21.0 (range, 0.8–52.3) years. During 3064 person-years, there were 34 first episodes of aneurysm rupture, giving an average annual incidence of 1.1%. Eighteen patients died on account of an initial or recurrent aneurysm rupture. The cumulative rate of bleeding was 10.5% (95% confidence interval [CI], 5.2–15.8) at 10 years, 23.0% (95% CI, 15.4–30.6) at 20 years, and 30.1% (95% CI, 21.3–38.9) at 30 years. None of the index aneurysms bled after a follow-up of 25 years. Cigarette smoking (adjusted hazard ratio, 2.44; 95% CI, 1.02–5.88), location of the aneurysm in the anterior communicating artery (adjusted hazard ratio, 3.73; 95% CI, 1.23–11.36), patient age inversely (0.96 per year, 95% CI, 0.92–1.00) and aneurysm diameter ≥7 mm (adjusted hazard ratio, 2.60; 95% CI, 1.13–5.98) independently predicted subsequent aneurysm rupture, as did alcohol consumption (1.27 per 100 g/week; 95% CI, 1.05–1.53;
P
<0.05), but only in univariable analysis.

Conclusions—
Cigarette smoking, patient age inversely, and the size and location of the unruptured intracranial aneurysm seem to be risk factors for aneurysm rupture. The risk of bleeding decreases with a very long-term follow-up.
The Stroke Impact Scale
Authors: Jenkinson Crispin , Fitzpatrick Ray , Crocker Helen , Peters Michele 
Published: July 2013

Background and Purpose—
The Stroke Impact Scale (SIS) covers 8 dimensions and a composite disability score. This study evaluates the SIS in the UK context, and develops a single index and an 8-item short form.

Methods—
Patients with a diagnosis of stroke were recruited through general practices in London and the North-West of England. Patients completed the SIS and the EQ-5D.

Results—

Internal consistency of the SIS dimensions and the disability score ranged from α 0.86 to 0.95. Complete data were available on 73 questionnaires (48.34%). Factor analysis suggested the 8 domains could be aggregated into a single index. A short-form SIS (SF-SIS) index was created by summing 1 item per dimension. Selected items were those that most highly correlated with their respective domain score (ρ ranged from 0.77–0.94,
P
<0.001). The SF-SIS index scores were highly correlated with those gained from the parent form (ρ=0.98;
P
<0.001). The correlation of the SIS index and SF-SIS index with the EQ-5D was identical (ρ=0.83;
P
<0.001). The disability score, whether scored from the dimensions of the SIS, or relevant items on the SF-SIS, were highly correlated (ρ=0.97;
P
<0.001).

Conclusions—
The SIS covers aspects of health, which are of importance to stroke patients, and the dimensions were found to have high levels of internal consistency in the UK context. The amount of incomplete data suggests that the length of the questionnaire may present a substantial patient burden. In comparison to the parent form the SF-SIS can accurately provide the disability score and overall index score with considerable brevity.
Systolic Blood Pressure During Acute Stroke Is Associated With Functional Status and Long-term Mortality in the Elderly
Authors: Weiss Avraham , Beloosesky Yichayaou , Kenett Ron S. , Grossman Ehud 
Published: July 2013

Background and Purpose—
The prognostic value of blood pressure (BP) levels during acute stroke has not been adequately studied. Most studies do not use continuous BP measurements, and patients are followed only for a short period. We designed a study to assess, with 24-hour BP monitoring (24H BPM), the impact of BP levels during the first day of stroke, on the short-term functional status and long-term mortality in elderly patients.

Methods—
We studied 177 patients with acute stroke (89 men), mean age 84±6 years. BP was measured on admission and 24H BPM was recorded within 24 hours of admission. After 7 days, patients were assessed for functional status according to the modified Rankin Scale and were subsequently followed up for mortality ≤5 years (mean, 2.07±1.48).

Results—

After 7 days, functional status improved and modified Rankin Scale decreased from 4.2 to 3.7. Follow-up analysis disclosed that 71 patients (27 men and 44 women) had died. Mortality rate was higher in women (50% versus 30%;
P
<0.01) and in patients with a history of congestive heart failure. Only average systolic BP, recorded by 24H BPM, predicted short-term functional status and long-term mortality. Cox proportional hazards model analysis demonstrated that age, sex, congestive heart failure, and average systolic BP >160 mm Hg, recorded by 24H BPM, were associated with increased mortality.

Conclusions—
High systolic BP recorded by 24H BPM on the first day of stroke was found to be associated with unfavorable short-term functional status and long-term mortality in elderly patients.
Unilateral Versus Bilateral Upper Limb Training After Stroke
Authors: van Delden A. (Lex) E.Q. , Peper C. (Lieke) E. , Nienhuys Kirsten N. , Zijp Nienke I. , Beek Peter J. , Kwakkel Gert 
Published: July 2013

Background and Purpose—
Unilateral and bilateral training protocols for upper limb rehabilitation after stroke represent conceptually contrasting approaches with the same ultimate goal. In a randomized controlled trial, we compared the merits of modified constraint-induced movement therapy, modified bilateral arm training with rhythmic auditory cueing, and a dose-matched conventional treatment. Modified constraint-induced movement therapy and modified bilateral arm training with rhythmic auditory cueing targeted wrist and finger extensors, given their importance for functional recovery. We hypothesized that modified constraint-induced movement therapy and modified bilateral arm training with rhythmic auditory cueing are superior to dose-matched conventional treatment.

Methods—
Sixty patients, between 1 to 6 months after stroke, were randomized over 3 intervention groups. The primary outcome measure was the Action Research Arm test, which was conducted before, directly after, and 6 weeks after intervention.

Results—
Although all groups demonstrated significant improvement on the Action Research Arm test after intervention, which persisted at 6 weeks follow-up, no significant differences in change scores on the Action Research Arm test were found between groups postintervention and at follow-up.

Conclusions—
Modified constraint-induced movement therapy and modified bilateral arm training with rhythmic auditory cueing are not superior to dose-matched conventional treatment or each other in improving upper limb motor function 1 to 6 months after stroke.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR1665.
Surgical Decompression for Space-Occupying Cerebral Infarction
Authors: Geurts Marjolein , van der Worp H. Bart , Kappelle L. Jaap , Amelink G. Johan , Algra Ale , Hofmeijer Jeannette 
Published: July 2013

Background and Purpose—
We assessed whether the effects of surgical decompression for space-occupying hemispheric infarction, observed at 1 year, are sustained at 3 years.

Methods—
Patients with space-occupying hemispheric infarction, who were enrolled in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial within 4 days after stroke onset, were followed up at 3 years. Outcome measures included functional outcome (modified Rankin Scale), death, quality of life, and place of residence. Poor functional outcome was defined as modified Rankin Scale >3.

Results—
Of 64 included patients, 32 were randomized to decompressive surgery and 32 to best medical treatment. Just as at 1 year, surgery had no effect on the risk of poor functional outcome at 3 years (absolute risk reduction, 1%; 95% confidence interval, −21 to 22), but it reduced case fatality (absolute risk reduction, 37%; 95% confidence interval, 14–60). Sixteen surgically treated patients and 8 controls lived at home (absolute risk reduction, 27%; 95% confidence interval, 4–50). Quality of life improved between 1 and 3 years in patients treated with surgery.

Conclusions—
In patients with space-occupying hemispheric infarction, the effects of decompressive surgery on case fatality and functional outcome observed at 1 year are sustained at 3 years.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN94237756.