bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Platelet GPVI Protects Against Myocardial Ischemia–Reperfusion Injury
Authors: Pachel Christina , Mathes Denise , Arias-Loza Anahi-Paula , Heitzmann Wolfram , Nordbeck Peter , Deppermann Carsten , Lorenz Viola , Hofmann Ulrich , Nieswandt Bernhard , Frantz Stefan 
Published: February 2016

Objective—
The objective of this study was to investigate the effects of platelet inhibition on myocardial ischemia–reperfusion (IR) injury.

Approach and Results—

Timely restoration of coronary blood flow after myocardial infarction is indispensable but leads to additional damage to the heart (myocardial IR injury). Microvascular dysfunction contributes to myocardial IR injury. We hypothesized that platelet activation during IR determines microvascular perfusion and thereby the infarct size in the reperfused myocardium. The 3 phases of thrombus formation were analyzed by targeting individual key platelet-surface molecules with monoclonal antibody derivatives: (1) adhesion (anti-glycoprotein [GP]-Ib), (2) activation (anti-GPVI), and (3) aggregation (anti-GPIIbIIIa) in a murine in vivo model of left coronary artery ligation (30 minutes of ischemia followed by 24 hours of reperfusion). Infarct sizes were determined by Evans Blue/2,3,5-triphenyltetrazolium chloride staining, infiltrating neutrophils by immunohistology. Anti-GPVI treatment significantly reduced infarct size versus control, whereas anti-GPIb or anti-GPIIbIIIa antibody fragments showed no significant differences. Mechanistically, anti-GPVI antibody–mediated reduction of infarct size was not because of impaired Ca
2+
signaling or platelet degranulation because mice deficient in store-operated calcium channels (stromal interaction molecule 1, ORAI1), α-granules (Nbeal2
−/−
), and dense granule release (Unc13d
−/−
) had similar infarct sizes as control animals. Protective effects of anti-GPVI treatment were accompanied by improved microperfusion. Leukocyte infiltration was reduced in both anti-GPVI and anti-GPIb-treated IR mice.

Conclusions—
Inhibition of platelet activation by an anti-GPVI antibody, but not inhibition of platelet adhesion or aggregation by an anti-GPIb or anti-GPIIbIIIa antibody significantly reduces infarct size. The reduction of the infarct size is primarily based on an improved microperfusion after anti-GPVI antibody treatment.
Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates
Authors: Kullo Iftikhar J. , Jouni Hayan , Austin Erin E. , Brown Sherry-Ann , Kruisselbrink Teresa M. , Isseh Iyad N. , Haddad Raad A. , Marroush Tariq S. , Shameer Khader , Olson Janet E. , Broeckel Ulrich , Green Robert C. , Schaid Daniel J. , Montori Victor M. , Bailey Kent R. 
Published: February 2016

Background—
Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels.

Methods and Results—

Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (
+
GRS). Participants in the
+
GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or
+
GRS (n=103). At the end of the study period, the
+
GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL;
P
=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (
P
=0.02) but not participants with low GRS (100.9±32.2 mg/dL;
P
=0.18). Statins were initiated more often in the
+
GRS group than in the CRS group (39% versus 22%,
P
<0.01). No significant differences in dietary fat intake and physical activity levels were noted.

Conclusions—
Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01936675.
Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis
Authors: Tomkins Amelia J. , Hood Rebecca J. , Pepperall Debbie , Null Christopher L. , Levi Christopher R. , Spratt Neil J. 
Published: February 2016

Background

Stroke associated with acute carotid occlusion is associated with poor effectiveness of tissue plasminogen activator (
tPA
) thrombolysis and poor prognosis. Rupture of atherosclerotic plaques resulting in vascular occlusions may occur on plaques, causing variable stenosis. We hypothesized that degree of stenosis may affect recanalization rates with
tPA
. Ultrasound+
tPA
(sonothrombolysis) has been shown to improve recanalization for intracranial occlusions but has not been tested for carotid occlusion. Our primary aim was to determine thrombolytic recanalization rates in a model of occlusion with variable stenosis, with a secondary aim to investigate sonothrombolysis in this model.

Methods and Results

Rat carotid arteries were crushed and focal stenosis created (25% baseline Doppler flow) with a silk‐suture tie invoking thrombosis and occlusion. To model mild or severe stenosis, the tie was released pretreatment or left in place. Animals were treated with
tPA
(10 mg/kg) or
tPA
+ultrasound (2‐MHz) in each stenosis model (n=7/group). Recanalization was assessed by Doppler flow. Thrombolytic recanalization rates were significantly higher in mild stenosis groups (71% versus 0% with severe stenosis;
P
<0.0001). Recanalization rates were not significantly higher with additional ultrasound in either model.

Conclusions
In this model, the degree of carotid stenosis had a large effect on thrombolytic recanalization. Sonothrombolysis using standard parameters for intracranial sonothrombolysis did not increase recanalization. Further testing is warranted. The degree of underlying stenosis may be an important predictor of thrombolytic recanalization, and clinical correlation of these findings may provide new approaches to treatment selection for patients with carotid occlusion.
Isolated Human Pulmonary Artery Structure and Function Pre‐ and Post‐Cardiopulmonary Bypass Surgery
Authors: Dora Kim A. , Stanley Christopher P. , Al Jaaly Emad , Fiorentino Francesca , Ascione Raimondo , Reeves Barnaby C. , Angelini Gianni D. 
Published: February 2016

Background
Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre–cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post–cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery.

Methods and Results
Pre‐ and post–cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration‐dependent vasoconstriction in 100% and 75% of pre‐ and post–cardiopulmonary bypass arteries, respectively. The endothelium‐dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre‐ and post–cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre–cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post–cardiopulmonary bypass biopsies.

Conclusions
We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium‐dependent dilation were significantly reduced in post–cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability.

Clinical Trial Registration

URL
:
http://www.isrctn.com/ISRCTN34428459
. Unique identifier:
ISRCTN
34428459.
Restoring Sinus Rhythm Improves Baroreflex Function in Patients With Persistent Atrial Fibrillation
Authors: Field Michael E. , Wasmund Stephen L. , Page Richard L. , Hamdan Mohamed H. 
Published: February 2016

Background

Studies have suggested that patients with atrial fibrillation (
AF
) have impairment in the baroreflex. It is not clear whether these findings are the result of the associated comorbid conditions or the arrhythmia itself. We hypothesized that
AF
is associated with impairment in baroreflex function and that the arrhythmia itself is a contributing factor.

Methods and Results

Twenty‐four patients with persistent
AF
referred for cardioversion were enrolled. A second group of patients with no history of
AF
matched for age and left ventricular ejection fraction was identified and served as the control group. In the
AF
group, baroreflex gain (
BRG
) was measured on the day of cardioversion (Day 1) and again at 30 days post‐cardioversion (Day 30) in patients who remained in sinus rhythm (
SR
). The clinical characteristics of patients with
AF
were not different than those of the control group. The mean
BRG
in the
AF
group on Day 1 was significantly lower than the mean
BRG
of the control group (5.2±3.6 versus 10.8±5.5 ms/mm Hg,
P
<0.05). Ten patients experienced
AF
recurrence before the 30‐day follow‐up and 14 patients remained in
SR
. In the group that remained in
SR
,
BRG
increased from 4.1±3.7 ms/mm Hg on Day 1 to 7.0±6.0 ms/mm Hg on Day 30 (
P
<0.01).

Conclusion

We have shown that
AF
is associated with impairment of the baroreflex and that restoration of
SR
improves
BRG
. Our data suggest that
AF
might be a contributing factor to the observed impairment in
BRG
and that restoring
SR
might help improve baroreflex function.
Ischemic Stroke in Children and Young Adults With Congenital Heart Disease
Authors: Mandalenakis Zacharias , Rosengren Annika , Lappas Georgios , Eriksson Peter , Hansson Per‐Olof , Dellborg Mikael 
Published: February 2016

Background

Patients with congenital heart disease (
CHD
) may be at increased risk of ischemic stroke due to residual shunts, arrhythmias, and other cardiovascular abnormalities. We studied the relative risk and potential factors for developing ischemic stroke in children and young adults with
CHD
in Sweden.

Methods and Results

All patients in the Swedish Patient Register with a diagnosis of
CHD
, born between 1970 and 1993, were identified and compared with 10 controls for each patient, matched for age, sex, and county and randomly selected from the general population. Follow‐up data through 2011 were collected for both groups. Of 25 985 children and young adults with
CHD
(51.5% male, 48.5% female), 140 (0.5%) developed ischemic stroke. The hazard ratio for
CHD
patients developing ischemic stroke was 10.8 (95%
CI
, 8.5–13.6) versus controls. All major Marelli groups had significantly increased risk, but because of small
CHD
‐group sizes, only atrial septal defect/patent foramen ovale, double‐inlet ventricle, and aortic coarctation displayed significantly increased risk. In multivariate analysis of
CHD
patients, congestive heart failure carried the highest risk for developing ischemic stroke (hazard ratio 6.9 [95%
CI
, 4.7–10.3]), followed by hypertension and atrial fibrillation, which were also significantly associated with increased risk of ischemic stroke.

Conclusions

The risk of developing ischemic stroke was almost 11 times higher in young patients with
CHD
than in the general population, although absolute risk is low. Cardiovascular comorbidities were strongly associated with the development of ischemic stroke in young
CHD
patients.
Association Between Time From Stroke Onset and Fluid-Attenuated Inversion Recovery Lesion Intensity Is Modified by Status of Collateral Circulation
Authors: Wouters Anke , Dupont Patrick , Christensen Soren , Norrving Bo , Laage Rico , Thomalla Götz , Albers Greg , Thijs Vincent , Lemmens Robin 
Published: February 2016

Background and Purpose—
In patients with acute stroke, the intensity of a fluid-attenuated inversion recovery (FLAIR) lesion in the region of diffusion restriction is associated with time from symptom onset. We hypothesized that collateral status as assessed by the hypoperfusion intensity ratio could modify the association between time from stroke onset and FLAIR lesion intensity.

Methods—

From the AX200 for ischemic stroke trial, 141 patients had appropriate FLAIR, diffusion-weighted imaging, and perfusion-weighted imaging. In the region of nonreperfused core, we calculated voxel-based relative FLAIR (rFLAIR) signal intensity. The hypoperfusion intensity ratio was defined as the ratio of the
T
max
>10 s lesion over the
T
max
>6 s lesion volume. A hypoperfusion intensity ratio threshold of ≤0.4 was used to dichotomize good versus poor collaterals. We studied the interaction between collateral status on the association between time from symptom onset and FLAIR intensity.

Results—

Time from symptom onset was associated with the rFLAIR intensity in the region of nonreperfused core (
B
=1.05; 95% confidence interval, 1.0–1.1). We identified an interaction between this association and collateral status; an association was present between time and rFLAIR intensity in patients with poor collaterals (
r
=0.53), but absent in patients with good collaterals (
r
=0.17;
P
=0.04).

Conclusions—
Our findings show that the relationship between time from symptom onset and rFLAIR lesion intensity depends on collateral status. In patients with good collaterals, the development of an rFLAIR-positive lesion is less dependent on time from symptom onset compared with patients with poor collaterals.
Potential Influence of Arctic Sea Ice to the Interannual Variations of East Asian Spring Precipitation*
Authors: Wu Zhiwei , Li Xinxin , Li Yanjie , Li Yun 
Published: February 2016

AbstractArctic sea ice (ASI) and its potential climatic impacts have received increasing attention during the past decades, yet the relevant mechanisms are far from being understood, particularly how anomalous ASI affects climate in midlatitudes. The spring precipitation takes up as much as 30% of the annual total and significantly influences agriculture in East Asia. Here, observed evidence and numerical experiment results show that the ASI variability in the Norwegian Sea and the Barents Sea in the preceding winter is intimately connected with interannual variations of the East Asian spring precipitation (EAP). The former can explain about 14% of the total variance of the latter. The ASI anomalies persist from winter through the ensuing spring and excite downstream teleconnections of a distinct Rossby wave train prevailing over the Eurasian continent. For the reduced ASI, such a wave train pattern is usually associated with an anomalous low pressure center over the Mongolian plateau, which accelerates the East Asian subtropical westerly jet. The intensified subtropical westerly jet, concurrent with lower-level convergence and upper-level divergence, enhances the local convection and consequently favors rich spring precipitation over East Asia. For the excessive ASI, the situation tends to be opposite. Given that seasonal prediction of the EAP remains a challenging issue, the winter ASI variability may provide another potential predictability source besides El Niño–Southern Oscillation.
The Arctic Ocean Spices Up
Authors: Timmermans Mary-Louise , Jayne Steven R. 
Published: February 2016

AbstractThe contemporary Arctic Ocean differs markedly from midlatitude, ice-free, and relatively warm oceans in the context of density-compensating temperature and salinity variations. These variations are invaluable tracers in the midlatitudes, revealing essential fundamental physical processes of the oceans, on scales from millimeters to thousands of kilometers. However, in the cold Arctic Ocean, temperature variations have little effect on density, and a measure of density-compensating variations in temperature and salinity (i.e., spiciness) is not appropriate. In general, temperature is simply a passive tracer, which implies that most of the heat transported in the Arctic Ocean relies entirely on the ocean dynamics determined by the salinity field. It is shown, however, that as the Arctic Ocean warms up, temperature will take on a new role in setting dynamical balances. Under continued warming, there exists the possibility for a regime shift in the mechanisms by which heat is transported in the Arctic Ocean. This may result in a cap on the storage of deep-ocean heat, having profound implications for future predictions of Arctic sea ice.
“Deep-Arvor”: A New Profiling Float to Extend the Argo Observations Down to 4000-m Depth
Authors: Le Reste Serge , Dutreuil Vincent , André Xavier , Thierry Virginie , Renaut Corentin , Le Traon Pierre-Yves , Maze Guillaume 
Published: February 2016

AbstractThe international Argo program, consisting of a global array of more than 3000 free-drifting profiling floats, has now been monitoring the upper 2000 m of the ocean for several years. One of its main proposed evolutions is to be able to reach the deeper ocean in order to better observe and understand the key role of the deep ocean in the climate system. For this purpose, Ifremer has designed the new “Deep-Arvor” profiling float: it extends the current operational depth down to 4000 m, and measures temperature and salinity for up to 150 cycles with CTD pumping continuously and 200 cycles in spot sampling mode. High-resolution profiles (up to 2000 points) can be transmitted and data are delivered in near–real time according to Argo requirements. Deep-Arvor can be deployed everywhere at sea without any preballasting operation and its light weight (~26 kg) makes its launching easy. Its design was done to target a cost-effective solution. Predefined spots have been allocated to add an optional oxygen sensor and a connector for an extra sensor. Extensive laboratory tests were successful. The results of the first at-sea experiments showed that the expected performances of the operational prototypes had been reached (i.e., to perform up to 150 cycles). Meanwhile, the industrialization phase was completed in order to manufacture the Deep-Arvor float for the pilot experiment in 2015. This paper details all the steps of the development work and presents the results from the at-sea experiments.
Prevalence and Characteristics of Positional Nystagmus in Normal Subjects
Authors: Martens Camilla , Goplen Frederik Kragerud , Nordfalk Karl Fredrik , Aasen Torbjørn , Nordahl Stein Helge Glad 
Published: February 2016

ObjectiveIn clinical practice, patients are often referred due to a finding of positional nystagmus that does not always appear to correlate with clinical symptoms of benign paroxysmal positional vertigo. To know when to consider nystagmus to be of clinical relevance, it is necessary to know the prevalence and characteristics of positional nystagmus in a healthy population.Study DesignCase series of 75 healthy subjects.SettingTwo tertiary referral centers in Norway.Subjects and MethodsSeventy‐five adult subjects aged 40 ± 13 years (mean ± SD; range, 21‐87) without a history of vertigo or balance disorder were included from 2013 to 2015. The subjects underwent 6 different standardized positional tests in a repositioning chair. Videonystagmography was used to record eye movements. Of 1350 recordings, 1329 were included and analyzed.ResultsPositional nystagmus was detected in 88% of the subjects. The most common finding was nystagmus in the Dix‐Hallpike position, which occurred in 55% of the subjects. The 95th percentile of the maximum slow‐phase velocity for each subject was found to be 5.06° per second (n = 54) in the horizontal plane and 6.48° per second (n = 48) in the vertical plane.ConclusionPositional nystagmus is a common finding in normal subjects and occurred in 88% of the healthy subjects in the present study. Horizontal direction‐changing apogeotropic or geotropic nystagmus may occur in asymptomatic subjects. However, nystagmus that is of the paroxysmal type or has a slow‐phase velocity greater than approximately 5° per second in the horizontal plane or 6.5° per second in the vertical plane should be considered outside the 95th percentile.
Mucinous Adenocarcinoma of the Salivary Gland
Authors: Farhood Zachary , Zhan Kevin Y. , Lentsch Eric J. 
Published: February 2016

ObjectiveTo describe the clinical, demographic, and prognostic features of salivary gland mucinous adenocarcinoma, a rare head and neck malignancy.Study DesignPopulation‐based national cancer registry analysis.SettingAcademic medical center.Subjects and MethodsA review was performed with the National Cancer Database from 1998 to 2012. Demographic, clinical, and survival characteristics were compiled and analyzed. Cox multivariate regression was used to identify predictors of survival. Log‐rank tests were used to test survival differences unless otherwise specified.ResultsA total of 170 cases were identified. The most common site of involvement was the parotid gland. Rates of nodal and distant metastases were 45.9% and 10.6%, respectively. High histologic grade was associated with nodal disease (P <. 001) and advanced‐stage disease (P =. 006). Overall 5‐ and 10‐year survival rates were 60% and 44%, respectively. Multivariate analysis found tumor size ≥2 cm (hazard ratio, 22.6; 95% confidence interval: 4.06‐126.09; P <. 001) and distant metastases (hazard ratio, 17.6; 95% confidence interval: 3.75‐82.68; P <. 001) to predict poor outcomes.ConclusionsMucinous adenocarcinoma of the salivary gland is a rare otolaryngic cancer. Regional metastases and advanced stage are more common with high histologic grade. Tumor size and distant metastases negatively influence survival.