bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathological comparison of biodegradable polymer and permanent polymer based sirolimus eluting stents in a porcine model of coronary stent implantation
Authors: Koppara Tobias , Joner Michael , Bayer Gerd , Steigerwald Kristin , Diener Tobias , Wittchow Eric 
Published: April 2012

SummaryBiodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (CypherTM) at 28,90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to CypherTM at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm2 vs. 3.1 ± 1.5 mm2, p=0.03 and 1.8 ± 1.2 mm2 vs. 3.0 ± 1.5 mm2, p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drugeluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to CypherTM may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.
Peroxisome proliferator-activated receptor-alpha agonists repress expression of thrombin-activatable fibrinolysis inhibitor by decreasing transcript stability
Authors: Masuda Yutaka , Saotome Dan , Takada Kimihiko , Sugimoto Katsuyoshi , Sasaki Tomoyuki , Ishii Hidemi 
Published: April 2012

SummaryThrombin-activatable fibrinolysis inhibitor (TAFI) (carboxypeptidase B2) is a plasma zymogen that is biosynthesised in the liver and released into the circulation. Activated TAFI is a prothrombotic factor which inhibits fibrin clot lysis. Cultured human hepatoma HepG2 cells were treated with peroxisome proliferator-activated receptor (PPAR)α, β or γ agonists, and the levels of TAFI antigen and mRNA (here, termed CPB2 mRNA) were measured. HepG2 cells treated with the PPARα agonist WY14643, but not agonists for PPARβ or PPARγ, decreased their release of TAFI antigen into the conditioned medium. In parallel, there were decreased levels of CPB2 mRNA and TAFI antigen in the cells. The WY14643-mediated decrease in CPB2 mRNA levels was accelerated by overexpression of PPARα and abolished by RNA interference of PPARA mRNA. CPB2 gene promoter activity was not influenced by treatment of the cells with WY14643. The half-life of the CPB2 transcript was shortened by treatment with WY14643 as compared with that of the control, and the decreased half-life of mRNA returned to control levels by treatment with a PPARα antagonist MK886 or transfection of PPARΑ-specific siRNA to WY14643-treated HepG2 cells. The present results suggest that PPARα agonists not only play a hypolipidaemic role, but also decrease the expression of TAFI, a prothrombotic factor, by decreasing stability of CPB2 transcripts.
Early Repolarization Is an Independent Predictor of Occurrences of Ventricular Fibrillation in the Very Early Phase of Acute Myocardial Infarction
Authors: Naruse Yoshihisa , Tada Hiroshi , Harimura Yoshie , Hayashi Mayu , Noguchi Yuichi , Sato Akira , Yoshida Kentaro , Sekiguchi Yukio , Aonuma Kazutaka 
Published: April 2012

Background—
Recent evidence has linked early repolarization (ER) to idiopathic ventricular fibrillation (VF) in patients without structural heart disease. However, no studies have clarified whether or not there is an association between ER and the VF occurrences after the onset of an acute myocardial infarction (AMI).

Methods and Results—

This study retrospectively included 220 consecutive patients with an AMI (57 female; mean age, 69 ± 11 years) in whom the 12-lead ECGs before the AMI onset could be evaluated. The patients were classified on the basis of a VF occurrence within 48 hours after the AMI onset. Early repolarization was defined as an elevation of the QRS-ST junction of >0.1 mV from baseline in at least 2 inferior or lateral leads, manifested as QRS slurring or notching. Twenty-one (10%) patients had a VF occurrence within 48 hours of the AMI onset. A multivariate analysis revealed that ER (odds ratio [OR], 7.31; 95% confidence interval [CI], 2.21–24.14;
P
<0.01), a time from the onset to admission of <180 minutes (OR, 3.77; 95% CI, 1.13–12.59;
P
<0.05), and a Killip class greater than I (OR, 13.60; 95% CI, 3.43–53.99;
P
<0.001) were independent predictors of VF occurrences. As features of the ER pattern, a J-point elevation in the inferior leads, greater magnitude of the J-point elevation, notched morphology of the ER, and ER with a horizontal/descending ST segment, all were significantly associated with a VF occurrence.

Conclusions—
The presence of ER increased the risk of VF occurrences within 48 hours after the AMI onset.
Predictors of Increased Intravenous Tissue Plasminogen Activator Use Among Hospitals Participating in the Massachusetts Primary Stroke Service Program
Authors: Rost Natalia S. , Smith Eric E. , Pervez Muhammad A. , Mello Philip , Dreyer Paul , Schwamm Lee H. 
Published: April 2012

Background—
We sought to determine if intravenous tissue plasminogen activator (IV tPA) use for acute ischemic stroke increased in Massachusetts in association with the Primary Stroke Service program, a statewide stroke center designation and quality improvement initiative.

Methods and Results—

We analyzed prospectively acquired data from the Massachusetts Department of Public Health between October 2004 and June 2008, including 10 045 consecutive emergency department–based acute ischemic stroke encounters arriving ≤3 hours after stroke onset at 69 participating Massachusetts PSS hospitals. The overall rate of IV tPA use was 854 of 3866 (22.1%) of patients arriving ≤2 hours of symptom onset. IV tPA use increased steadily from 2005 (the first full year of the program) to 2008 (18.4%, 21.9%, 22.6%, 25.5%;
P
=0.001). Patients treated with IV tPA were more likely to be younger (72.3±14.1 versus 74.7±14.0 years,
P
<0.005) and to have presented after emergency medical services rerouting in July 2005 (96% versus 94%,
P
=0.009). Patients who arrived at hospitals with a performance achievement award from the Get With The Guidelines-Stroke program were more likely to receive IV tPA after versus before award recognition (28.1% versus 22.3%,
P
<0.001).

Conclusions—
In this nearly complete capture of statewide data, rates of IV tPA improved significantly in Massachusetts from 2005 to 2008 in association with a state Primary Stroke Service designation program. Further studies are needed to confirm that treatment disparities exist for older acute ischemic stroke patients and that the rates of thrombolysis have increased above and beyond secular trends.
Risk of Intracerebral Hemorrhage in Patients With Cerebral Microbleeds Undergoing Endovascular Intervention
Authors: Soo Yannie O.Y. , Siu Deyond Y.W. , Abrigo Jill , Yu Simon , Ng Nick , Ahuja Anil T. , Wong Lawrence K.S. , Leung Thomas W. 
Published: April 2012

Background and Purpose—
Cerebral microbleeds (CMBs) on MRI gradient echo images are hemosiderin deposits, which may predict intracerebral hemorrhage (ICH). The risk of ICH in patients with CMBs could be exacerbated by the use of antithrombotics. The purpose of our study is to prospectively evaluate the risk of ICH in patients with ischemic stroke who receive dual antiplatelet therapy for endovascular intervention.

Methods—
We analyzed MRI of 133 patients admitted consecutively for intra- and extracranial stenting for symptomatic large artery atherosclerosis who received aspirin and clopidogrel. Quantity and location of CMBs were recorded by neuroradiologists independent from the angioplasty team. The primary end point was symptomatic ICH as evident in CT of the brain within 12 weeks of procedure.

Results—

CMBs were identified in 23 patients. Mean number of CMBs was 2.3±1.6. Four patients had >5 CMBs. Forty-seven patients had intracranial stents, 84 patients had extracranial stents, and 2 patients had both intracranial and extracranial stents. There was no difference in risk of symptomatic ICH between those with (4.3%) and without CMBs (5.5%) patient with CMBs (
P
=1.000).

Conclusions—
The presence of a small number of CMBs does not cause a large increase in the short-term risk of symptomatic ICH in patients with ischemic stroke who undergo endovascular intervention with dual antiplatelet therapy. The risk of ICH in patients with ≥5 CMBs, however, remains unclear. Further studies with a larger sample size of patients with multiple CMBs are needed.
Timing of Intra-Arterial Neural Stem Cell Transplantation After Hypoxia–Ischemia Influences Cell Engraftment, Survival, and Differentiation
Authors: Rosenblum Sahar , Wang Nancy , Smith Tenille N. , Pendharkar Arjun V. , Chua Joshua Y. , Birk Harjus , Guzman Raphael 
Published: April 2012

Background and Purpose—
Intra-arterial neural stem cell (NSC) transplantation shows promise as a minimally invasive therapeutic option for stroke. We assessed the effect of timing of transplantation on cell engraftment, survival, and differentiation.

Methods—
Mouse NSCs transduced with a green fluorescent protein and renilla luciferase reporter gene were transplanted into animals 6 and 24 hours and 3, 7, and 14 days after hypoxia–ischemia (HI). Bioluminescent imaging was used to assess cell survival at 6 hours and 4 and 7 days after transplantation. Immunohistochemistry was used to assess NSC survival and phenotypic differentiation 1 month after transplantation. NSC receptor expression and brain gene expression were evaluated using real-time reverse transcription–quantitative polymerase chain reaction to elucidate mechanisms of cell migration. Boyden chamber assays were used to assess cell migratory potential in vitro.

Results—

NSC transplantation 3 days after HI resulted in significantly higher cell engraftment and survival at 7 and 30 days compared with all other groups (
P
<0.05). Early transplantation at 6 and 24 hours after HI resulted in significantly higher expression of glial fibrillary acidic protein (
P
=0.0140), whereas late transplantation at 7 and 14 days after HI resulted in higher expression of β-tubulin (
P
<0.0001). Corroborating the high cell engraftment 3 days after HI was robust expression of vascular cell adhesion molecule-1, CCL2, and CXCL12 in brain homogenates 3 days after HI.

Conclusion—
Intra-arterial transplantation 3 days after HI results in the highest cell engraftment. Early transplantation of NSCs leads to greater differentiation into astrocytes, whereas transplantation at later time points leads to greater differentiation into neurons.
Delayed Administration of a Small Molecule Tropomyosin-Related Kinase B Ligand Promotes Recovery After Hypoxic–Ischemic Stroke
Authors: Han Jullet , Pollak Julia , Yang Tao , Siddiqui Mohammad R. , Doyle Kristian P. , Taravosh-Lahn Kereshmeh , Cekanaviciute Egle , Han Alex , Goodman Jeremy Z. , Jones Britta , Jing Deqiang , Massa Stephen M. , Longo Frank M. , Buckwalter Marion S. 
Published: April 2012

Background and Purpose—
Stroke is the leading cause of long-term disability in the United States, yet no drugs are available that are proven to improve recovery. Brain-derived neurotrophic factor stimulates neurogenesis and plasticity, processes that are implicated in stroke recovery. It binds to both the tropomyosin-related kinase B and p75 neurotrophin receptors. However, brain-derived neurotrophic factor is not a feasible therapeutic agent, and no small molecule exists that can reproduce its binding to both receptors. We tested the hypothesis that a small molecule (LM22A-4) that selectively targets tropomyosin-related kinase B would promote neurogenesis and functional recovery after stroke.

Methods—
Four-month-old mice were trained on motor tasks before stroke. After stroke, functional test results were used to randomize mice into 2 equally, and severely, impaired groups. Beginning 3 days after stroke, mice received LM22A-4 or saline vehicle daily for 10 weeks.

Results—
LM22A-4 treatment significantly improved limb swing speed and accelerated the return to normal gait accuracy after stroke. LM22A-4 treatment also doubled both the number of new mature neurons and immature neurons adjacent to the stroke. Drug-induced differences were not observed in angiogenesis, dendritic arborization, axonal sprouting, glial scar formation, or neuroinflammation.

Conclusions—
A small molecule agonist of tropomyosin-related kinase B improves functional recovery from stroke and increases neurogenesis when administered beginning 3 days after stroke. These findings provide proof-of-concept that targeting of tropomyosin-related kinase B alone is capable of promoting one or more mechanisms relevant to stroke recovery. LM22A-4 or its derivatives might therefore serve as “pro-recovery” therapeutic agents for stroke.
The Cost-Effectiveness of Primary Stroke Centers for Acute Stroke Care
Authors: Guzauskas Gregory F. , Boudreau Denise M. , Villa Kathleen F. , Levine Steven R. , Veenstra David L. 
Published: April 2012

Background and Purpose—
Primary stroke centers (PSC) have demonstrated improved survival in patients with acute ischemic stroke (AIS). The objective of this study was to evaluate the cost-effectiveness of treating AIS patients in a PSC compared with a nonPSC hospital setting.

Methods—
We developed a decision analytic model to project the lifetime outcomes and costs of 2 hypothetical cohorts of 75 AIS patients. Clinical data were derived from a recent observational study comparing PSC- and nonPSC-admitted patients, clinical trials, longitudinal cohort studies, and health state preference studies. Cost data were based on Medicare reimbursement and other published sources. We used a healthcare payer perspective, and the primary outcomes were incremental life expectancy, quality-adjusted life years, and healthcare costs. We performed sensitivity and scenario analyses to evaluate uncertainty in the results.

Results—
Admission to a PSC resulted in a gain of 0.22 years of life (95% credible range [CR], 0.12–0.33) and 0.15 quality-adjusted life years (95% CR, 0.08–0.23) per patient, at a cost of $3600 (95% CR, $2400–$5000) per patient, compared with admission to a nonPSC hospital. The incremental cost/quality-adjusted life year gained was $24 000, and all probabilistic simulation results were below the $100 000/quality-adjusted life year threshold. In scenario analyses accounting for as few as 7 and as many as 500 AIS patients/year per PSC, cost-effectiveness improved as the number of AIS patients admitted per year increased.

Conclusions—
Our study indicates that care at a PSC for patients with AIS is cost-effective and improves outcomes across a wide range of possible scenarios.
Effects of Blood Pressure Lowering on Intracranial and Extracranial Bleeding in Patients on Antithrombotic Therapy
Authors: Arima Hisatomi , Anderson Craig , Omae Teruo , Woodward Mark , MacMahon Stephen , Mancia Giuseppe , Bousser Marie-Germaine , Tzourio Christophe , Rodgers Anthony , Neal Bruce , Chalmers John 
Published: April 2012

Background and Purpose—
Observational studies demonstrate strong associations between blood pressure and bleeding complications of antithrombotic therapy. The objective was to determine whether blood pressure lowering reduces risks of bleeding in patients on antithrombotic therapy.

Methods—
This is a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial. A total of 6105 patients with cerebrovascular disease were randomly assigned to either active treatment (perindopril±indapamide) or placebo(s). The outcomes were intracranial and extracranial bleeding.

Results—
There were 4876 (80%) patients on antithrombotic therapy at baseline. Over a mean follow-up of 3.9 years, 119 intracranial and 123 extracranial bleeding events were observed. Among patients with and without antithrombotic therapy, active treatment lowered blood pressure by 8.9/4.0 and 9.3/3.8 mm Hg and reduced the risks of intracranial bleeding by 46% (95% CI, 7%–69%) and 70% (39%–85%), respectively. However, active treatment did not reduce the risks of extracranial bleeding significantly in either group. Among patients on antithrombotic therapy, the lowest risk of intracranial bleeding was observed in participants with the lowest follow-up systolic blood pressure levels (median, 113 mm Hg).

Conclusions—
Blood pressure lowering provides protection against intracranial bleeding among patients with cerebrovascular disease including those receiving antithrombotic therapy.

Clinical Trial Registration Information—
This trial was not registered because patients were enrolled before July 1, 2005.
No Increased Risk of Symptomatic Intracerebral Hemorrhage After Thrombolysis in Patients With European Cooperative Acute Stroke Study (ECASS) Exclusion Criteria
Authors: Cronin Carolyn A. , Shah Nikeith , Morovati Tanya , Hermann Lisa D. , Sheth Kevin N. 
Published: April 2012

Background and Purpose—
The European Cooperative Acute Stroke Study (ECASS) III trial used additional exclusion criteria not present in current guidelines for thrombolytic therapy in the United States (age >80 years; National Institutes of Health Stroke Scale >25, combination of previous stroke and diabetes, aggressive measures required to control blood pressure [intravenous infusion], and oral anticoagulant treatment). We tested the hypothesis that thrombolysis is not safe in patients with 1 of the additional exclusion criteria.

Methods—
All patients treated with intravenous tissue-type plasminogen activator for acute stroke at our center between June 2006 and June 2010 were identified (n=191), and stratified based on presence of each of the exclusion criteria. Primary outcomes were rate of symptomatic intracerebral hemorrhage and in-hospital mortality. Additionally, patients with and without symptomatic intracerebral hemorrhage were analyzed for differences in baseline characteristics.

Results—

No exclusion criterion was associated with increased risk of symptomatic intracerebral hemorrhage. Symptomatic intracerebral hemorrhage was associated with atrial fibrillation (5 of 9 [55%], versus 35 of 182 [19.2%];
P
=0.021), larger final infarct volume (mean 173 mL
3
versus 42 mL
3
;
P
=0.0002), and elevated glucose (mean 166 mg/dL versus 127 mg/dL;
P
=0.038). There was higher mortality in patients >80 years (5 of 31 [16%] versus 6 of 160 [4%];
P
=0.0186) and those with National Institutes of Health Stroke Scale >25 (2 of 5 [40%] versus 7 of 159 [4.4%];
P
=0.025).

Conclusions—
In our cohort, none of the more stringent exclusion criteria from ECASS III were associated with increased risk of symptomatic intracerebral hemorrhage. Prospective randomized studies are needed clarify the safety and efficacy of tissue-type plasminogen activator in these patients through all treatment time windows.
Diagnosis of Tropical Biases and the MJO from Patterns in the MERRA Analysis Tendency Fields
Authors: Mapes Brian E. , Bacmeister Julio T. 
Published: April 2012

Abstract
The Modern-Era Reanalysis for Research and Applications (MERRA) is realistic, including its Madden–Julian oscillation (MJO), which the underlying model [Goddard Earth Observing System, version 5 (GEOS-5)] lacks. In the MERRA budgets, analysis tendencies (ATs) make evolution realistic despite model shortcomings. The ATs are the negative of physical process errors, if dynamical tendencies are accurate. Pattern resemblances between ATs and physical tendencies suggest which processes are erroneous. The authors examined patterns of tropical ATs in four dimensions and found several noteworthy features. Temperature AT profiles show that moist physics has erroneous sharp cooling at 700 hPa, a signature of misplaced melting and perhaps excessive precipitation evaporation. This excites a distinctive (fingerprint) erroneous short vertical wavelength temperature structure, perhaps a cause of the GEOS-5 too-slow convectively coupled waves. The globe’s largest AT of 200-hPa wind stems from overactive heating over the intra-Americas seas region in summer, with the same moist physics fingerprint. The erroneous heating produces a baroclinic vortex that is countered by ATs opposing its temperature and momentum fields in a thermal wind balanced sense. Lack of restraint in the deep convection scheme is also indicated in MJO composites, where the water vapor AT is anomalously positive on the leading edge, indicating a premature vapor sink. Since GEOS-5 lacks an MJO, this diagnosis suggests that the transition from shallow to deep convection (moistening to drying) is crucial in the real-world MJO. This is not news, but its diagnosis by ATs provides an objective, repeatable way to measure the effect that could be a useful guide in model development.
Some Observational Evidence for Dry Soils Supporting Enhanced Relative Humidity at the Convective Boundary Layer Top
Authors: Westra D. , Steeneveld G. J. , Holtslag A. A. M. 
Published: April 2012

Abstract
The tendency of the relative humidity at the top of a clear convective boundary layer (RHtop) is studied as an indicator of cloud formation over a semiarid region within the conceptual framework introduced by Ek and Holtslag. Typically the tendency of RHtop increases if the evaporative fraction at the land surface increases, which supports boundary layer moistening but only when boundary layer growth is limited by atmospheric factors. This regime was supported by Cabauw observations in the original study. Here, new observational evidence that the tendency of RHtop can also increase as the surface becomes more dry, as is consistent with another regime of the conceptual framework, is provided. The observations used are from the African Monsoon Multidisciplinary Analyses (AMMA) intensive observational campaign near Niamey, Niger, 20–25 June 2006. In addition, the authors evaluate whether various versions of the Weather Research and Forecasting single-column model confirm the different regimes of the conceptual framework for a typical day in the AMMA campaign. It appears that the model confirms that dryer soils can support cloud formation.