bluuebunny/crossref_metadata_2025_split huggingface dataset:
F-Actin–Anchored Focal Adhesions Distinguish Endothelial Phenotypes of Human Arteries and Veins
Authors: van Geemen Daphne , Smeets Michel W.J. , van Stalborch Anne-Marieke D. , Woerdeman Leonie A.E. , Daemen Mat J.A.P. , Hordijk Peter L. , Huveneers Stephan 
Published: July 2014

Objective—
Vascular endothelial–cadherin- and integrin-based cell adhesions are crucial for endothelial barrier function. Formation and disassembly of these adhesions controls endothelial remodeling during vascular repair, angiogenesis, and inflammation. In vitro studies indicate that vascular cytokines control adhesion through regulation of the actin cytoskeleton, but it remains unknown whether such regulation occurs in human vessels. We aimed to investigate regulation of the actin cytoskeleton and cell adhesions within the endothelium of human arteries and veins.

Approach and Results—
We used an ex vivo protocol for immunofluorescence in human vessels, allowing detailed en face microscopy of endothelial monolayers. We compared arteries and veins of the umbilical cord and mesenteric, epigastric, and breast tissues and find that the presence of central F-actin fibers distinguishes the endothelial phenotype of adult arteries from veins. F-actin in endothelium of adult veins as well as in umbilical vasculature predominantly localizes cortically at the cell boundaries. By contrast, prominent endothelial F-actin fibers in adult arteries anchor mostly to focal adhesions containing integrin-binding proteins paxillin and focal adhesion kinase and follow the orientation of the extracellular matrix protein fibronectin. Other arterial F-actin fibers end in vascular endothelial–cadherin-based endothelial focal adherens junctions. In vitro adhesion experiments on compliant substrates demonstrate that formation of focal adhesions is strongly induced by extracellular matrix rigidity, irrespective of arterial or venous origin of endothelial cells.

Conclusions—
Our data show that F-actin–anchored focal adhesions distinguish endothelial phenotypes of human arteries from veins. We conclude that the biomechanical properties of the vascular extracellular matrix determine this endothelial characteristic.
Incremental Prognostic Significance of the Elevated Levels of Pentraxin 3 in Patients With Heart Failure With Normal Left Ventricular Ejection Fraction
Authors: Matsubara Junichi , Sugiyama Seigo , Nozaki Toshimitsu , Akiyama Eiichi , Matsuzawa Yasushi , Kurokawa Hirofumi , Maeda Hirofumi , Fujisue Koichiro , Sugamura Koichi , Yamamoto Eiichiro , Matsui Kunihiko , Jinnouchi Hideaki , Ogawa Hisao 
Published: July 2014

Background

Pentraxin 3 (
PTX
3) is a novel inflammatory marker produced by various cell types including those of the vasculature and the heart. The relationship between inflammatory markers and prognosis of patients with heart failure with normal ejection fraction (
HFNEF
) remains unknown. We investigated whether plasma
PTX
3 levels can predict future cardiovascular events in patients with
HFNEF
.

Methods and Results

Plasma PTX3, high‐sensitivity C‐reactive protein, and B‐type natriuretic peptide levels were measured prospectively in 360 stable patients with HFNEF. The subsequent incidence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction (MI), unstable angina pectoris, nonfatal ischemic stroke, hospitalization for heart failure decompensation, and coronary revascularization, was determined. During a mean 30‐month follow‐up, 106 patients experienced cardiovascular events. These events were more frequent in patients with high plasma PTX3 levels (>3.0 ng/
mL
) than low levels (≤3.0 ng/
mL
). Multivariable Cox hazard analysis showed that PTX3 (hazard ratio: 1.16; 95% CI: 1.05 to 1.27;
P
<0.01) and B‐type natriuretic peptide (hazard ratio: 1.08; 95% CI: 1.03 to 1.14;
P
<0.001), but not high‐sensitivity C‐reactive protein levels, were significant predictors of future cardiovascular events. Multivariable Cox analysis with the forced inclusion model, including 5 previously identified prognostic factors, found that PTX3 was a significant predictor of cardiovascular events (hazard ratio: 1.16; 95% CI: 1.06 to 1.27;
P
<0.01). The C‐statistics for cardiovascular events substantially increased from 0.617 to 0.683 when PTX3 was added to the 5 previously identified prognostic factors.

Conclusions

High plasma
PTX
3 levels, but not other inflammatory markers, are correlated with future cardiovascular events in patients with
HFNEF
.
PTX
3 may be a useful biomarker for assessment of risk stratification in
HFNEF
.

Clinical Trial Registration

URL
:
http://www.umin.ac.jp
; Unique identifier:
UMIN
000002170.
Mammalian Target of Rapamycin Cell Signaling Pathway Contributes to the Protective Effects of Ischemic Postconditioning Against Stroke
Authors: Xie Rong , Wang Peng , Cheng Michelle , Sapolsky Robert , Ji Xunming , Zhao Heng 
Published: July 2014

Background and Purpose—
Whether the mammalian target of rapamycin (mTOR) pathway is protective against brain injury from stroke or is detrimental is controversial, and whether it is involved in the protective effects of ischemic postconditioning (IPC) against stroke is unreported. Our study focuses on the protective role of mTOR against neuronal injury after stroke with and without IPC.

Methods—
We used both an in vitro oxygen–glucose deprivation model with a mixed neuronal culture and hypoxic postconditioning, as well as an in vivo stroke model with IPC. Rapamycin, a specific pharmacological inhibitor of mTOR, and mTOR short hairpin RNA lentiviral vectors were used to inhibit mTOR activity. A lentiviral vector expressing S6K1, a downstream molecule of mTOR, was used to confirm the protective effects of mTOR. Infarct sizes were measured and protein levels were examined by Western blot.

Results—
We report that stroke resulted in reduced levels of phosphorylated proteins in the mTOR pathway, including S6K1, S6, and 4EBP1, and that IPC increased these proteins. mTOR inhibition, both by the mTOR inhibitor rapamycin and by mTOR short hairpin RNA, worsened ischemic outcomes in vitro and in vivo and abolished the protective effects of hypoxic postconditioning and IPC on neuronal death in vitro and brain injury size in vivo. Overexpression of S6K1 mediated by lentiviral vectors significantly attenuated brain infarction.

Conclusions—
mTOR plays a crucial protective role in brain damage after stroke and contributes to the protective effects of IPC.
α4 Integrin Is a Regulator of Leukocyte Recruitment After Experimental Intracerebral Hemorrhage
Authors: Hammond Matthew D. , Ambler William G. , Ai Youxi , Sansing Lauren H. 
Published: July 2014

Background and Purpose—
Intracerebral hemorrhage (ICH) is swiftly followed by an inflammatory response. A key component of this response is the recruitment of leukocytes into the brain, which promotes neurological injury in rodent models. However, the mechanisms by which leukocytes transmigrate across the endothelium into the injured brain are unclear. The present study examines leukocyte adhesion molecules (α4 integrin, L-selectin, and αLβ2 integrin) on 4 leukocyte subtypes to determine which are important for leukocyte recruitment after ICH.

Methods—
We used the blood injection mouse model of ICH, whereby 25 μL of blood was injected into the striatum. Flow cytometry was used to quantify leukocyte populations and adhesion molecule expression in brain and blood. An α4 integrin–blocking antibody was administered to evaluate the contribution of α4 integrin in leukocyte migration and neurological injury.

Results—
α4 integrin was elevated on all leukocyte populations in brain after ICH, whereas L-selectin was unchanged and αLβ2 was increased only on T cells. Antagonism of α4 resulted in decreased leukocyte transmigration and lessened neurobehavioral disability.

Conclusions—
α4 integrin is an important cell adhesion molecule involved in neuroinflammation after ICH.
A Dark Side of Subcortical Diffusion-Weighted Lesions?
Authors: Kvistad Christopher Elnan , Oygarden Halvor , Logallo Nicola , Moen Gunnar , Thomassen Lars , Waje-Andreassen Ulrike , Naess Halvor 
Published: July 2014

Background and Purpose—
Diffusion-weighted imaging (DWI) is highly accurate in identifying and locating ischemic stroke injury. Few studies using DWI have investigated large subcortical infarctions (LSIs). We aimed to study clinical characteristics, cause, and outcome in patients with ischemic stroke with LSI diagnosed on DWI and compare these with those who had lacunar DWI lesions or DWI lesions located elsewhere.

Methods—
Patients with stroke admitted between February 2006 and July 2013 were prospectively registered in a stroke database and examined with DWI. Patients with DWI lesions classified as LSI (subcortical, ≥15 mm) were compared with those with lacunar lesions (subcortical, <15 mm, lacunar infarction [LI]), cortical lesions (cortical infarction [CI]), or no LSI, which included LI, CI, mixed cortical–subcortical, cerebellar, brain stem, and combined lesion locations.

Results—

A total of 1886 patients with ischemic stroke were included, of which 128 patients (6.8%) had LSI, 317 (16.8%) LI, and 544 (28.8%) CI. The no LSI group included 1758 patients. Occlusive pathology in the proximal middle cerebral artery was more frequent in patients with acute stroke with LSI. Lacunar syndrome was associated with LSI when compared with CI and no LSI. Unknown cause was frequent in the LSI group (60.4%) and independently associated with LSI in the LSI versus LI (
P
<0.001), LSI versus CI (
P
=0.002), and LSI versus no LSI population (
P
<0.001). LSI was independently associated with unfavorable outcome, whether compared with LI (
P
=0.002), CI (
P
<0.001), or no LSI (
P
=0.002).

Conclusions—
LSI is associated with distinct clinical characteristics, unknown cause, and unfavorable outcome, which separates this stroke entity from patients with lacunar subcortical DWI lesions or DWI lesions located elsewhere.
Tropospheric Rossby Wave Breaking and Variability of the Latitude of the Eddy-Driven Jet
Authors: Garfinkel Chaim I. , Waugh Darryn W. 
Published: July 2014

AbstractA dry general circulation model is used to investigate the connections between Rossby wave breaking and the latitude of the midlatitude tropospheric eddy-driven jet. An ensemble of experiments is constructed in which the jet latitude is influenced by a midlatitude tropospheric temperature anomaly that resembles observed climate change and by the imposition of a stratospheric polar vortex, and the distribution of Rossby wave breaking frequency is examined for each experiment. The shift in wave breaking per degree latitude of jet shift is then compared for three different sources of jet movement: the tropospheric baroclinic forcing imposed in midlatitudes, the imposition of a stratospheric polar vortex, and the internal variability of the midlatitude eddy-driven jet. It is demonstrated that all three sources of jet movement produce a similar change in Rossby wave breaking frequency per degree of jet shift. Hence, it is difficult (if not impossible) to isolate the ultimate cause behind the shift in Rossby wave breaking in response to the two external forcings.
Variability explained by strength, body composition and gait impairment in activity and participation measures for children with cerebral palsy: a multicentre study
Authors: Oeffinger Donna , Gorton George , Hassani Sahar , Sison-Williamson Mitell , Johnson Barbara , Whitmer Megan , Romness Mark , Kryscio Dick , Tylkowski Chester , Bagley Anita 
Published: July 2014

Objective: To determine the amount of variability in scores on activity and participation measures used to assess ambulatory individuals with cerebral palsy explained by strength, body composition, gait impairment and participant characteristics. Design: Multicentre prospective cross-sectional study. Setting: Seven paediatric–orthopaedic specialty hospitals. Participants: Three hundred and seventy-seven ambulatory individuals (241 males, 136 females) with cerebral palsy, Gross Motor Function Classification System (GMFCS) levels I–III (I = 148, II = 153, III = 76), ages 8–18 years (mean 12 years 9 months, SD 2 years 8 months). Methods: Participants completed assessments of GMFCS level, patient history, lower extremity muscle strength, Gross Motor Function Measure (GMFM-66), Pediatric Outcomes Data Collection Instrument (PODCI), instrumented gait analysis, 1 minute walk test, Timed Up-and-Go and body composition. Multiple linear regression and bootstrap analyses were performed for each outcome measure, stratified by GMFCS level. Results: The amount of variability in outcome measures explained by participant characteristics, strength, and gait impairment ranged from 11% to 50%. Gait impairment was the most common predictor variable and frequently explained the greatest variance across all outcome measures and GMFCS levels. As gait impairment increased, scores on outcome measures decreased. Strength findings were inconsistent and not a primary factor. Body composition contributed minimally (<4%) in explaining variability. Participant characteristics (cerebral palsy type, gestational age and age at walking onset), were significant predictor variables in several models. Conclusions: Variability in outcome measure scores is multifaceted and only partially explained by strength and gait impairment illustrating the challenges of attempting to explain variation within this heterogeneous population. Clinicians treating individuals with cerebral palsy should consider this when developing treatment paradigms.
Reduced information processing speed as primum movens for cognitive decline in MS
Authors: Van Schependom Jeroen , D’hooghe Marie B , Cleynhens Krista , D’hooge Mieke , Haelewyck Marie-Claire , De Keyser Jacques , Nagels Guy 
Published: July 2014

Background: Cognitive impairment affects half of the multiple sclerosis (MS) patient population and is an important contributor to patients’ daily activities. Most cognitive impairment studies in MS are, however, cross-sectional or/and focused on the early disease stages. Objective: We aim to assess the time course of decline of different cognitive domains. Methods: We collected neuropsychological data on 514 MS patients to construct Kaplan-Meier survival curves of the tests included in the Neuropsychological Screening Battery for MS (NSBMS) and the Symbol Digit Modalities Test (SDMT). Cox-proportional hazard models were constructed to examine the influence of MS onset type, age at onset, gender, depression and level of education on the time course, expressed as age or disease. Results: Survival curves of tests focusing on information processing speed (IPS) declined significantly faster than tests with less specific demands of IPS. Median age for pathological decline was 56.2 years (95% CI: 54.4–58.2) on the SDMT and 63.9 years (95% CI: 60–66.9) on the CLTR, a memory task. Conclusion: In conclusion, IPS is the cognitive domain not only most widely affected by MS but it is also the first cognitive deficit to emerge in MS.
Prolonged grief in caregivers of community-dwelling dementia patients
Authors: Passoni Serena , Toraldo Alessio , Villa Barbara , Bottini Gabriella 
Published: July 2014

Objectives: To estimate the frequency of prolonged grief disorder (PGD) in 90 primary caregivers of patients with dementia who live in the community dwelling in Milan and to identify the relationship between grief intensity (GI) and other caregiver variables; another aim was to clarify the role of the objective cognitive and functional impairment of the patients and the level of deterioration perceived by caregivers. Design: Cross-sectional study. Results: In all, 16.7% of caregivers had PGD. Caregiver variables increasing GI and the risk of developing PGD were burden, anxiety, and some sociodemographic features. The objective level of patient’s deterioration was irrelevant for PGD probability/GI, while the deterioration level perceived by the caregiver increased PGD probability and GI. Conclusions: Caregivers of patients with dementia may experience grief symptoms that are associated with low educational level, high level of burden and anxiety, and high perceived deterioration of their demented relatives’ cognitive and functional abilities.
The relationship between timely delivery of vocational rehabilitation services and subsequent federal disability benefit application and receipt
Authors: Schimmel Hyde Jody , Honeycutt Todd , Stapleton David 
Published: July 2014

Abstract
Federal/state vocational rehabilitation (VR) agencies offer services to individuals with disabilities that may help them remain in the labor force and avoid entering Social Security Administration (SSA) disability programs. We assess how the availability of VR services within an agency at the time an individual applies to receive VR services is related to subsequent application and receipt of SSA disability benefits. We find that individuals have a higher likelihood of subsequently applying for and receiving disability benefits when they apply in months that the VR agency serves a lower percentage of applicants or has a longer average wait for services.

JEL codes

H55, H75, J29
Comparison of clinical outcome variables in patients with and without etomidate-facilitated anesthesia induction ahead of major cardiac surgery: a retrospective analysis
Authors: Heinrich Sebastian , Schmidt Joachim , Ackermann Andreas , Moritz Andreas , Harig Frank , Castellanos Ixchel 
Published: July 2014

Abstract
Introduction
It is well known that etomidate may cause adrenal insufficiency. However, the clinical relevance of adrenal suppression after a single dose of etomidate remains vague. The aim of this study was to investigate the association between the administration of a single dose of etomidate or an alternative induction regime ahead of major cardiac surgery and clinical outcome parameters associated with adrenal suppression and onset of sepsis.

Methods
The anesthesia and intensive care unit (ICU) records from patients undergoing cardiac surgery over five consecutive years (2008 to 2012) were retrospectively analyzed. The focus of the analysis was on clinical parameters like mortality, ventilation hours, renal failure, and sepsis-linked serum parameters. Multivariate analysis and Cox regression were applied to derive the results.

Results
In total, 3,054 patient records were analyzed. A group of 1,775 (58%) patients received a single dose of etomidate; 1,279 (42%) patients did not receive etomidate at any time. There was no difference in distribution of age, American Society of Anesthesiologists physical score, duration of surgery, and Acute Physiology and Chronic Health Evaluation II score. Postoperative data showed no significant differences between the two groups in regard to mortality (6.8% versus 6.4%), mean of mechanical ventilation hours (21.2 versus 19.7), days in the ICU (2.6 versus 2.5), hospital days (18.7 versus 17.4), sepsis-associated parameters, Sequential Organ Failure Assessment score, and incidence of renal failure. Administration of etomidate showed no significant influence (P = 0.6) on hospital mortality in the multivariate Cox analysis.

Conclusions
This study found no evidence for differences in key clinical outcome parameters based on anesthesia induction with or without administration of a single dose of etomidate. In consequence, etomidate might remain an acceptable option for single-dose anesthesia induction.
Below-Knee Arterial Calcification in Type 2 Diabetes: Association With Receptor Activator of Nuclear Factor κB Ligand, Osteoprotegerin, and Neuropathy
Authors: Bourron Olivier , Aubert Carole Elodie , Liabeuf Sophie , Cluzel Philippe , Lajat-Kiss Frédérique , Dadon Michel , Komajda Michel , Mentaverri Romuald , Brazier Michel , Pierucci Antoine , Morel Florence , Jacqueminet Sophie , Massy Ziad A. , Hartemann Agnès 
Published: July 2014

Context:
Calcification of the arterial wall in diabetes contributes to the arterial occlusive process occurring below the knee. The osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) system is suspected to be involved in the calcification process.

Objective:
The aim of the study was to investigate whether there is a link between arterial calcification in type 2 diabetes and 1) conventional cardiovascular risk factors, 2) serum RANKL and OPG levels, and 3) neuropathy.

Patients and Methods:
We objectively scored, in a cross-sectional study, infrapopliteal vascular calcification using computed tomography scanning in 198 patients with type 2 diabetes, a high cardiovascular risk, and a glomerular filtration rate &gt;30 mL/min. Color duplex ultrasonography was performed to assess peripheral arterial occlusive disease, and mediacalcosis. Peripheral neuropathy was defined by a neuropathy disability score &gt;6. RANKL and OPG were measured in the serum by routine chemistry.

Results:
Below-knee arterial calcification was associated with arterial occlusive disease. In multivariate logistic regression analysis, the variables significantly and independently associated with the calcification score were age (odds ratio [OR] = 1.08; 95% confidence interval [CI] = 1.04–1.13; P &lt; .0001), male gender (OR = 3.53; 95% CI = 1.54–8.08; P = .003), previous cardiovascular disease (OR = 2.78; 95% CI = 1.39–5.59; P = .005), and neuropathy disability score (per 1 point, OR = 1.21; 95% CI = 1.05–1.38; P = .006). The association with ln OPG, significantly associated with calcification score in univariate analysis (OR = 3.14; 95% CI = 1.05–9.40; P = .045), was no longer significant in multivariate analysis. RANKL and OPG/RANKL were not significantly associated with the calcification score.

Conclusions:
Below-knee arterial calcification severity is clearly correlated with peripheral neuropathy severity and with several usual cardiovascular risk factors, but not with serum RANKL level.
A Reversible Albumin-Binding Growth Hormone Derivative is Well Tolerated and Possesses a Potential Once-Weekly Treatment Profile
Authors: Rasmussen Michael Højby , Olsen Minna W. Brændholt , Alifrangis Lene , Klim Søren , Suntum Mette 
Published: July 2014

Abstract

Context:
Human growth hormone (hGH) replacement therapy currently requires daily sc injections for years/lifetime, which may be both inconvenient and distressing for patients. NNC0195–0092 is a novel hGH derivative intended for once-weekly treatment of GH deficiency.
A noncovalent albumin binding moiety is attached to the hGH backbone. Clearance is reduced as a consequence of a reversible binding to circulating serum albumin, which prolongs the pharmacodynamic (PD) effect.

Objective:
To evaluate safety, local tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose (SD) and multiple doses (MD) of NNC0195–0092.

Setting and Design:
Randomized, single-center, placebo-controlled, double-blind, SD/MD, dose-escalation trial of 105 healthy male subjects. NNC0195–0092 sc administration: Five cohorts of eight subjects received one dose of NNC0195–0092 (0.01–0.32 mg/kg) (n = 6) or placebo (n = 2). Sixteen subjects (equal numbers of Japanese and non-Asian) received once-weekly doses of NNC0195–0092 (0.02–0.24 mg/kg; n=12) or placebo (n=4) for 4 weeks. Blood samples were drawn for assessment of safety, PK, IGF-1, and IGF binding protein 3 profiles and anti-drug antibodies.

Results:
SD and MD of NNC0195–0092 were well tolerated at all dose levels. No safety concerns or local tolerability issues were identified. A dose-dependent IGF-1 response was observed. IGF-1 profiles suggest that NNC0195–0092 may be suitable for once-weekly dosing, with a clinically relevant dose ≤0.08 mg/kg/week. No differences in PK and PD were observed between Japanese and non-Asian subjects.

Conclusions:
SD and MD of NNC0195–0092 administered to healthy Japanese and non-Asian male subjects were well tolerated at all doses. The present trial suggests that NNC0195–0092 has the potential for an efficacious, well-tolerated, once-weekly GH treatment.