bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Galectin-1 and Galectin-3 as Novel Partners for Von Willebrand Factor
Authors: Saint-Lu Nathalie , Oortwijn Beatrijs D. , Pegon Julie N. , Odouard Soline , Christophe Olivier D. , de Groot Philip G. , Denis Cécile V. , Lenting Peter J.
Published: January 2012

Objective—

Although von Willebrand factor (VWF) is a heavily glycosylated protein, its potential to associate with glycan-binding proteins is poorly investigated. Here, we explored its interaction with the glycan-binding proteins galectin-1 and galectin-3.

Methods and Results—

Immunofluorescence analysis using Duolink proximity ligation assays revealed that VWF colocalizes with galectin-1 and galectin-3 in endothelial cells, both before and after stimulation of endothelial cells. Moreover, galectin-1 was found along the typical VWF bundles that are released by endothelial cells. Galectin-1 and galectin-3 could be coprecipitated with VWF from plasma in immunoprecipitation assays, whereas plasma levels of galectin-1 and galectin-3 were significantly reduced in VWF-deficient mice. Binding studies using purified proteins confirmed that VWF could directly interact with both galectins, predominantly via its
N
-linked glycans. In search of the physiological relevance of the VWF-galectin interaction, we found that inhibition of galectins in in vitro perfusion assays was associated with increased VWF-platelet string formation, a phenomenon that was reproduced in galectin-1/galectin-3 double-deficient mice. These mice were also characterized by a more rapid formation of initial thrombi following ferric chloride–induced injury.

Conclusion—

We have identified galectin-1 and galectin-3 as novel partners for VWF, and these proteins may modulate VWF-mediated thrombus formation.
Anti-Inflammatory Effects of Nicotinic Acid in Human Monocytes Are Mediated by GPR109A Dependent Mechanisms
Authors: Digby Janet E. , Martinez Fernando , Jefferson Andrew , Ruparelia Neil , Chai Joshua , Wamil Malgorzata , Greaves David R. , Choudhury Robin P.
Published: January 2012

Objective—

Nicotinic acid (NA) treatment has been associated with benefits in atherosclerosis that are usually attributed to effects on plasma lipoproteins. The NA receptor GPR109A is expressed in monocytes and macrophages, suggesting a possible additional role for NA in modulating function of these immune cells. We hypothesize that NA has the potential to act directly on monocytes to alter mediators of inflammation that may contribute to its antiatherogenic effects in vivo.

Methods and Results—

In human monocytes activated by Toll-like receptor (TLR)-4 agonist lipopolysaccharide, NA reduced secretion of proinflammatory mediators: TNF-α (by 49.2±4.5%); interleukin-6 (by 56.2±2.8%), and monocyte chemoattractant protein-1 (by 43.2±3.1%) (
P
<0.01). In TLR2 agonist, heat-killed Listeria monocytogenes-activated human monocytes, NA reduced secretion of TNF-α (by 48.6±7.1%), interleukin-6 (by 60.9±1.6%), and monocyte chemoattractant protein-1 (by 59.3±5.3%) (
P
<0.01; n=7). Knockdown of GPR109A by siRNA resulted in a loss of this anti-inflammatory effect in THP-1 monocytes. However, inhibition of prostaglandin D
2
receptor by MK0524 or COX2 by NS398 did not alter the anti-inflammatory effects of NA observed in activated human monocytes. Preincubation of THP-1 monocytes with NA 0.1 mmol/L reduced phosphorylated IKKβ by 42±2% (
P
<0.001) IKB-α by 54±14% (
P
<0.01). Accumulation of nuclear p65 NF-κB in response to lipopolysaccharide treatment was also profoundly inhibited, by 89±1.3% (n=4;
P
<0.01). NA potently inhibited monocyte adhesion to activated HUVEC, and VCAM, mediated by the integrin, very late antigen 4. Monocyte chemotaxis was also significantly reduced (by 45.7±1.2%;
P
<0.001).

Conclusion—

NA displays a range of effects that are lipoprotein-independent and potentially antiatherogenic. These effects are mediated by GPR109A and are independent of prostaglandin pathways. They suggest a rationale for treatment with NA that is not dependent on levels of plasma cholesterol and possible applications beyond the treatment of dyslipidemia.
FGF19 Signaling Cascade Suppresses
APOA
Gene Expression
Authors: Chennamsetty Indumathi , Claudel Thierry , Kostner Karam M. , Trauner Michael , Kostner Gert M.
Published: January 2012

Objective—

Lipoprotein(a) is a highly atherogenic lipoprotein, whose metabolism is poorly understood. Currently no safe drugs exists that lower elevated plasma lipoprotein(a) concentrations. We therefore focused on molecular mechanisms that influence apolipoprotein(a) (APOA) biosynthesis.

Methods and Results—

Transgenic human
APOA
mice (tg-
APO
mice) were injected with 1 mg/kg of recombinant human fibroblast growth factor 19 (FGF19). This led to a significant reduction of plasma APOA and hepatic expression of
APOA
. Incubation of primary hepatocytes of tg-
APOA
mice with FGF19 induced ERK1/2 phosphorylation and, in turn, downregulated APOA expression. Repression of APOA by FGF19 was abrogated by specific ERK1/2 phosphorylation inhibitors. The FGF19 effect on APOA was attenuated by transfection of primary hepatocytes with siRNA against the FGF19 receptor 4 (FGFR4). Using promoter reporter assays, mutation analysis, gel shift, and chromatin immune-precipitation assays, an Ets-1 binding element was identified at –1630/–1615bp region in the human
APOA
promoter. This element functions as an Elk-1 binding site that mediates repression of
APOA
transcription by FGF19.

Conclusion—

These findings provide mechanistic insights into the transcriptional regulation of human
APOA
by FGF19. Further studies in the human system are required to substantiate our findings and to design therapeutics for hyper lipoprotein(a).
Site-Specific MicroRNA-92a Regulation of Krüppel-Like Factors 4 and 2 in Atherosusceptible Endothelium
Authors: Fang Yun , Davies Peter F.
Published: January 2012

Objective—

Endothelial transcription factors Krüppel-like factor 4 (KLF4) and KLF2 are implicated in protection against atherogenesis. Steady-state microRNA (miR) regulation of KLFs in vivo is accessible by screening region-specific endothelial miRs and their targets.

Methods and Results—

A subset of differentially expressed endothelial miRs was identified in atherosusceptible versus protected regions of normal swine aorta. In silico analyses predicted highly conserved binding sites in the 3′-untranslated region (3′UTR) of KLF4 for 5 miRs of the subset (miR-26a, -26b, -29a, -92a, and -103) and a single binding site for a miR-92a complex in the 3′UTR of KLF2. Of these, only miR-92a knockdown and knock-in resulted in responses of KLF4 and KLF2 expression in human arterial endothelial cells. Dual luciferase reporter assays demonstrated functional interactions of miR-92a with full-length 3′UTR sequences of both KLFs and with the specific binding elements therein. Two evolutionarily conserved miR-92a sites in KLF4 3′UTR and 1 site in KLF2 3′UTR were functionally validated. Knockdown of miR-92a in vitro resulted in partial rescue from cytokine-induced proinflammatory marker expression (monocyte chemotactic protein 1, vascular cell adhesion molecule-1, E-selectin, and endothelial nitric oxide synthase) that was attributable to enhanced KLF4 expression. Leukocyte-human arterial endothelial cell adhesion experiments supported this conclusion. In swine aortic arch endothelium, a site of atherosusceptibility where miR-92a expression was elevated, both KLFs were expressed at low levels relative to protected thoracic aorta.

Conclusion—

miR-92a coregulates KLF4 and KLF2 expression in arterial endothelium and contributes to phenotype heterogeneity associated with regional atherosusceptibility and protection in vivo.
Sympathetic Nervous System Regulates Bone Marrow–Derived Cell Egress Through Endothelial Nitric Oxide Synthase Activation
Authors: Récalde Alice , Richart Adèle , Guérin Coralie , Cochain Clément , Zouggari Yasmine , Yin Kiave Ho Wang , Vilar José , Drouet Isabelle , Lévy Bernard , Varoquaux Odile , Silvestre Jean-Sébastien
Published: January 2012

Objective—

Catecholamines have been shown to control bone marrow (BM)–derived cell egress, yet the cellular and molecular mechanisms involved in this effect and their subsequent participation to postischemic vessel growth are poorly understood.

Methods and Results—

Tyrosine hydroxylase mRNA levels, as well as dopamine (DA) and norepinephrine (NE) contents, were increased in the ischemic BM of mice with right femoral artery ligation. Angiographic score, capillary density, and arteriole number were markedly increased by treatments with DA (IP, 50 mg/kg, 5 days) or NE (IP, 2.5 mg/kg, 5 days). Using chimeric mice lethally irradiated and transplanted with BM-derived cells from green fluorescent protein mice, we showed that DA and NE enhanced by 70% (
P
<0.01) and 62% (
P
<0.001), respectively, the number of green fluorescent protein–positive BM-derived cells in ischemic tissue and promoted their ability to differentiate into cells with endothelial and inflammatory phenotypes. Similarly, both DA and NE increased the in vitro differentiation of cultured BM-derived cells into cells with endothelial phenotype. This increase was blunted by the nitric oxide synthase inhibitor
N
ω
-nitro-
l
-arginine methyl ester. DA and NE also upregulated the number of CD45-positive cells in blood 3 days after ischemia and that of macrophages in ischemic tissue 21 days after ischemia. Of interest, DA and NE increased BM endothelial nitric oxide synthase (eNOS) mRNA levels and were unable to promote BM-derived cell mobilization in chimeric eNOS-deficient mice lethally irradiated and transplanted with BM-derived cells from wild-type animals. Furthermore, administration of a β2 adrenergic agonist (clenbuterol, IP, 2 mg/kg, 5 days) and that of a dopaminergic D1/D5 receptor agonist (SKF-38393, IP, 2.5 mg/kg, 5 days) also enhanced BM-derived cell mobilization and subsequently postischemic vessel growth.

Conclusion—

These results unravel, for the first time, a major role for the sympathetic nervous system in BM-derived cell egress through stromal eNOS activation.
Cardiac Myosin Binding Protein-C Mutations in Families With Hypertrophic Cardiomyopathy
Authors: Page Stephen P. , Kounas Stavros , Syrris Petros , Christiansen Michael , Frank-Hansen Rune , Andersen Paal Skytt , Elliott Perry M. , McKenna William J.
Published: January 2012

Background—

Small selected cohort studies suggest that mutations in the cardiac myosin binding protein-C (MYBPC3) gene cause late-onset, clinically benign hypertrophic cardiomyopathy (HCM). The aim of this study was to test this hypothesis in a large series of families with HCM associated with MYBPC3 mutations.

Methods and Results—

The initial study population comprised 57 probands with 42 mutations (26 [61.9%] novel) in MYBPC3. Missense mutations (15, 45.6%) were the most frequent, and multiple mutations occurred in 4 (7.0%) probands. Another 110 mutation carriers were identified during familial evaluation; 38 were clinically affected with left ventricular hypertrophy ≥13 mm. Disease penetrance was, therefore, incomplete (56.9% in all mutation carriers, 34.5% in relatives), related to age (38.4% <40 versus 68.6% ≥40 years,
P
<0.001), and was greater in males than females (65.1% versus 48.1%,
P
=0.03). In 9 families (25 individuals) with the R502W mutation, there was marked heterogeneity in age at diagnosis (5 to 80 years), pattern of hypertrophy (11 none, 9 asymmetrical, 3 concentric, 1 apical, 1 eccentric), and prognosis (premature sudden death in 2 individuals compared with survival to advanced age in 6 individuals). During follow up of 7.9+/−4.5 years, in 82 clinically affected individuals the annual risk of sudden death and all cause mortality was 0.46% and 0.93% per year, respectively.

Conclusions—

Disease expression in families with HCM related to MYBPC3 mutations shows marked heterogeneity with incomplete, age-related, and gender specific penetrance. Importantly, complex genetic status is observed and should be considered when mutation analysis and cascade screening is used in the evaluation of at risk family members.
Assessment of Long-Term Effects of Irbesartan on Heart Failure With Preserved Ejection Fraction as Measured by the Minnesota Living With Heart Failure Questionnaire in the Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial
Authors: Rector Thomas S. , Carson Peter E. , Anand Inder S. , McMurray John J. , Zile Michael R. , McKelvie Robert S. , Komajda Michel , Kuskowski Michael , Massie Barry M. ,   for the I-PRESERVE Trial Investigators
Published: January 2012

Background—

The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used in a large, multinational, randomized, placebo-controlled trial to measure adverse effects of heart failure with preserved ejection fraction (HF-PEF) on patients' lives and the effects of irbesartan.

Methods and Results—

Patients with symptomatic HF-PEF were randomly assigned to irbesartan (up to 300 mg daily) or placebo. The MLHFQ was administered at baseline (n=3605), month 6 (n=3137), month 14 (n=2904), and the end of study (median, 56 months, n=2205). Baseline MLHFQ scores of 43±21 indicated that HF-PEF had a substantial adverse effects. Estimated retest reliability was 0.80. Baseline MLHFQ scores were associated with other measures of the severity of heart failure including symptoms, signs of congestion, cardiac structure, and time to hospitalizations or deaths attributed to heart failure. Slight improvement in shortness of breath or fatigue was associated with significant improvement in MLHFQ scores (−5.9 and −5.0,
P
<0.0001). Compared with placebo, further improvement in MLHFQ scores was not observed with irbesartan after 6 months (mean adjusted difference, 0.4; 95% confidence interval, −0.8 to 1.7), 14 months (0.5; 95% confidence interval, −0.9 to 1.8), or the end of study (2.0; 95% confidence interval, −4.1 to 0.01).

Conclusions—

The MLHFQ scores are a reliable, valid, and sensitive measure of the adverse impact of HF-PEF on patients' lives. Irbesartan did not substantially improve MLHFQ scores during a long period of follow-up.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00095238.
Combined Cardiac Magnetic Resonance Imaging and C-Reactive Protein Levels Identify a Cohort at Low Risk for Defibrillator Firings and Death
Authors: Wu Katherine C. , Gerstenblith Gary , Guallar Eliseo , Marine Joseph E. , Dalal Darshan , Cheng Alan , Marbán Eduardo , Lima João A.C. , Tomaselli Gordon F. , Weiss Robert G.
Published: January 2012

Background—

Annually, ≈80 000 Americans receive guideline-based primary prevention implantable cardioverter-defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on left ventricular ejection fraction, which lacks sensitivity and specificity. Because scar-related myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance identification of myocardial heterogeneity improves risk stratification through (1) its association with adverse cardiac events independent of clinical factors and biomarker levels and (2) its ability to identify particularly high- and low-risk subgroups.

Methods and Results—

In 235 patients with chronic ischemic and nonischemic cardiomyopathy with a left ventricular ejection fraction of ≤35% undergoing clinically indicated primary prevention ICD implantation, gadolinium-enhanced cardiac magnetic resonance was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone [GZ]) and dense core scar. Serum high-sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary end point was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 (19%) patients at a 3.6-year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ, and core scar were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (
P
<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7% per year event rate), whereas those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1% per year,
P
<0.001.

Conclusions—

In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk for adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00181233.
Thioredoxin Interacting Protein Promotes Endothelial Cell Inflammation in Response to Disturbed Flow by Increasing Leukocyte Adhesion and Repressing Kruppel-Like Factor 2
Authors: Wang Xiao-Qun , Nigro Patrizia , World Cameron , Fujiwara Keigi , Yan Chen , Berk Bradford C.
Published: January 2012

Rationale:

Endothelial cells (EC) at regions exposed to disturbed flow (d-flow) are predisposed to inflammation and the subsequent development of atherosclerosis. We previously showed that thioredoxin interacting protein (TXNIP) was required for tumor necrosis factor-mediated expression of vascular cell adhesion molecule-1.

Objective:

We sought to investigate the role of TXNIP in d-flow-induced cell adhesion molecule expression and leukocyte interaction with vessels, and the mechanisms by which TXNIP suppresses athero-protective gene expression.

Methods and Results:

Using en face staining of mouse aorta, we found a dramatic increase of TXNIP in EC at sites exposed to d-flow as compared to steady flow. EC-specific TXNIP (EC-TXNIP) knockout mice showed significant decreases in vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 mRNA expression in the d-flow regions of mouse aorta. Intravital microscopy of mesenteric venules showed that leukocyte rolling time was decreased, whereas rolling velocity was increased significantly in EC-TXNIP knockout mice. In vitro experiments using a cutout flow chamber to generate varying flow patterns showed that increased TXNIP was required for d-flow-induced EC-monocyte adhesion. Furthermore, we found that the expression of Kruppel-like factor 2, a key anti-inflammatory transcription factor in EC, was inhibited by TXNIP. Luciferase and chromatin immunoprecipitation assays showed that TXNIP was present within a repressing complex on the Kruppel-like factor 2 promoter.

Conclusions:

These data demonstrate the essential role for TXNIP in mediating EC-leukocyte adhesion under d-flow, as well as define a novel mechanism by which TXNIP acts as a transcriptional corepressor to regulate Kruppel-like factor 2-dependent gene expression.
Coronary Vasospasm Induced in Transgenic Mouse With Increased Phospholipase C-δ1 Activity
Authors: Shibutani Shuji , Osanai Tomohiro , Ashitate Toshihiro , Sagara Shigeki , Izumiyama Kei , Yamamoto Yuko , Hanada Kenji , Echizen Takashi , Tomita Hirofumi , Fujita Takeshi , Miwa Takeshi , Matsubara Hiroaki , Homma Yoshimi , Okumura Ken
Published: January 2012

Background—

We reported that phospholipase C (PLC)-δ1 activity was enhanced 3-fold in patients with coronary spastic angina. We detected variant PLC-δ1 with replacement of arginine 257 by histidine (R257H) showing increased enzymatic activity. We tested the hypothesis that increased PLC-δ1 activity causes enhanced coronary vasomotility.

Methods and Results—

We generated transgenic (TG) mice with human R257H variant PLC-δ1 in vascular smooth muscle cells. PLC enzymatic activity in the coronary artery was increased by 2.57 and 1.89 times, respectively, in homozygous and heterozygous TG compared with wild-type (WT) mice. ST elevation after ergometrine occurred in 17 of 18 homozygous TG, 6 of 20 heterozygous TG, and 3 of 22 WT mice (
P
<0.01, homozygous TG versus WT;
P
<0.05, homozygous TG versus heterozygous TG;
P
=NS, heterozygous TG versus WT). ST elevation was associated with bradyarrhythmias in homozygous TG mice. Focal coronary artery narrowing was documented with the microvascular filling technique in 3 of 5 homozygous TG mice after ergometrine but not in any of 7 WT mice (
P
<0.05). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in homozygous TG mice (
P
<0.01) but not in heterozygous TG or WT mice. Coronary perfusion pressure increase after prostaglandin F
2α
was similar among homozygous TG, heterozygous TG, and WT mice. Cultured rat aortic smooth muscle cells transfected with variant PLC-δ1 showed a higher PLC activity than those with WT PLC-δ1 (
P
<0.05) and furthermore showed greater intracellular Ca
2+
response to acetylcholine in variant than in WT PLC-δ1 (
P
<0.05).

Conclusions—

Increased PLC-δ1 activity enhances coronary vasomotility such as that seen in patients with coronary spastic angina.
The Albumin in Subarachnoid Hemorrhage (ALISAH) Multicenter Pilot Clinical Trial
Authors: Suarez Jose I. , Martin Renee H. , Calvillo Eusebia , Dillon Catherine , Bershad Eric M. , MacDonald R. Loch , Wong John , Harbaugh Robert
Published: January 2012

Background and Purpose—

Human albumin has been shown to exert neuroprotective effects in animal models of cerebral ischemia and humans with various intracranial pathologies. We investigated the safety and tolerability of 25% human albumin in patients with subarachnoid hemorrhage.

Methods—

The Albumin in Subarachnoid Hemorrhage (ALISAH) Pilot Clinical Trial was an open-label, dose-escalation study. We intended to study 4 different dosages of albumin of increasing magnitude (0.625 g/kg: Tier 1; 1.25 g/kg: Tier 2; 1.875 g/kg: Tier 3; and 2.5 g/kg: Tier 4). Each dosage was to be given to 20 adult patients. Treatment was administered daily for 7 days. We investigated the maximum tolerated dose of albumin based on the rate of severe-to-life-threatening heart failure and anaphylactic reaction and functional outcome at 3 months.

Results—

We treated 47 adult subjects: 20 in Tier 1; 20 in Tier 2; and 7 in Tier 3. We found that doses ranging up to 1.25 g/kg/day×7 days were tolerated by patients without major dose-limiting complications. We also found that outcomes trended toward better responses in those subjects enrolled in Tier 2 compared with Tier 1 (OR, 3.0513; CI, 0.6586–14.1367) and with the International Intraoperative Hypothermia for Aneurysm Surgery Trial cohort (OR, 3.1462; CI, 0.9158–10.8089).

Conclusions—

Albumin in doses ranging up to 1.25 g/kg/day×7 days was tolerated by patients with subarachnoid hemorrhage without major complications and may be neuroprotective. Based on these results, planning of the ALISAH II, a Phase III, randomized, placebo-controlled trial to test the efficacy of albumin, is underway.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00283400.
Metabolic Syndrome and Colorectal Cancer
Authors: Kontou Niki , Psaltopoulou Theodora , Soupos Nick , Polychronopoulos Evangelos , Xinopoulos Dimitrios , Linos Athena , Panagiotakos Demosthenes B.
Published: January 2012

The effect of Mediterranean diet on colorectal cancer, in the presence of the metabolic syndrome, was evaluated in 250 patients with first developed cancer (63 ± 12 years, 59% males) and 250 age–gender-matched controls. Adherence to the Mediterranean diet was evaluated with the modified-MedDietScore (theoretical range 0-75), while assessment of the metabolic syndrome (MetS) was based on the third Adult Treatment Panel ([ATP III] National Cholesterol Education Program) criteria. Presence of MetS (1.66, 95% confidence interval [CI] 1.02, 2.69), age (4.25, 95% CI 2.33, 7.77), smoking (1.85, 95% CI 1.27, 2.70), and family history of colorectal cancer (3.37, 95% CI 1.69, 6.75) had a detrimental effect, whereas adherence to the Mediterranean diet (0.88, 95% CI 0.84, 0.92) and body mass index (0.93, 95%CI 0.89, 0.98) had a protective role regarding colorectal cancer. Mediterranean diet had the same effect in relation to colorectal cancer, in both participants with (0.84, 95% CI 0.76, 0.93) and without MetS (0.89, 95% CI 0.85, 0.94).
Size and Subclasses of Low-Density Lipoproteins in Patients With Obstructive Sleep Apnea
Authors: Sopkova Zuzana , Berneis Kaspar , Rizzo Manfredi , Spinas Giatgen A. , Dorkova Zuzana , Tisko Radovan , Tkacova Ruzena
Published: January 2012

Patients with obstructive sleep apnea (OSA) have proatherogenic dyslipidemia. We analyzed predictors of low-density lipoproteins' (LDLs) size in patients with OSA. In a cross-sectional study including 58 participants with OSA (30 without the metabolic syndrome [MetS] and 28 with MetS), we evaluated the size of LDL by gradient gel electrophoresis. Compared with patients without the MetS, those with MetS showed lower LDL size ( P = .007), due to a reduction in large LDL-I particles ( P = .002) and an increase in small, dense LDL-IIIA ( P = .048) and LDL-IIIB ( P = .037). The size of LDL correlated inversely with age ( r = −.268, P = .042) and serum triglycerides ( r = −.364, P = .005), and positively with serum high-density lipoprotein cholesterol levels ( r = .335, P = .010). In multiple regression analysis, the presence of the MetS was the only independent predictor of LDL size ( P = 0.015). In patients with OSA, MetS is an independent predictor of LDL size and subclasses, whereas the severity of OSA does not contribute independently to alterations in LDL phenotype.
Enriched job design, high involvement management and organizational performance: The mediating roles of job satisfaction and well-being
Authors: Wood Stephen , Van Veldhoven Marc , Croon Marcel , de Menezes Lilian M
Published: January 2012

The relationship between organizational performance and two dimensions of the ‘high performance work system’ – enriched job design and high involvement management (HIM) – is widely assumed to be mediated by worker well-being. We outline the basis for three models: mutual-gains, in which employee involvement increases well-being and this mediates its positive relationship with performance; conflicting outcomes, which associates involvement with increased stress for workers, accounting for its positive performance effects; and counteracting effects, which associates involvement with increased stress and dissatisfaction, reducing its positive performance effects. These are tested using the UK’s Workplace Employment Relations Survey 2004. Job satisfaction mediates the relationship between enriched job design and four performance indicators, supporting the mutual gains model; but HIM is negatively related to job satisfaction and this depresses a positive relationship between HIM and the economic performance measures, supporting a counteracting effects model. Finally, HIM is negatively related to job-related anxiety–comfort and enriched job design is unrelated to it.
This Is Our Land: Land, Policy, Resistance, and Everyday Life in Colonial Southern Ghana, 1894–7
Authors: Nti Kwaku
Published: January 2012

The colonial government attempted to implement the Crown Lands Bill between 1894 and 1897 in Southern Ghana. Among other things, it sought to take control of what was described as ‘waste lands’ and later ‘public lands.’ This article focuses on resistance to these bills in which the Aborigines’ Rights Protect Society (ARPS) played a leading role on behalf of Southern Ghana. This was one of many precedents to the build-up of tension between the people and the colonial establishment. Among other things, the article examines the ramblings within a colonial administration that attempted to push through its policies against a background of resolute resistance. This led to reluctance on the part of some colonial officers to enforce the policy. The argument is that there was an effective collaboration between the Western-educated elite and the people of coastal Southern Gold Coast in the resistance to these bills. They used official letters of protests, newspaper articles, editorials, and demonstrations to express their dislike for the colonial land policy. In addition, they sent delegations to the colonial government in their effort to resist the attempt to take over ‘waste lands’ and later ‘public lands.’ Furthermore, this article argues that the conflict had to do with the different conceptions of land. While the colonial government saw it as part of the economic and political trappings of power, the people of Southern Ghana saw land as a cultural and religious resource that gave them the needed connection with the ancestors in their everyday life.
Chlorhexidine Inhibits the Activity of Dental Cysteine Cathepsins
Authors: Scaffa P.M.C. , Vidal C.M.P. , Barros N. , Gesteira T.F. , Carmona A.K. , Breschi L. , Pashley D.H. , Tjäderhane L. , Tersariol I.L.S. , Nascimento F.D. , Carrilho M.R.
Published: January 2012

The co-expression of MMPs and cysteine cathepsins in the human dentin-pulp complex indicates that both classes of enzymes can contribute to the endogenous proteolytic activity of dentin. Chlorhexidine (CHX) is an efficient inhibitor of MMP activity. This study investigated whether CHX could also inhibit cysteine cathepsins present in dentin. The inhibitory profile of CHX on the activity of dentin-extracted and recombinant cysteine cathepsins (B, K, and L) was monitored in fluorogenic substrates. The rate of substrate hydrolysis was spectrofluorimetrically measured, and inhibitory constants were calculated. Molecular docking was performed to predict the binding affinity between CHX and cysteine cathepsins. The results showed that CHX inhibited the proteolytic activity of dentin-extracted cysteine cathepsins in a dose-dependent manner. The proteolytic activity of human recombinant cathepsins was also inhibited by CHX. Molecular docking analysis suggested that CHX strongly interacts with the subsites S2 to S2′ of cysteine cathepsins B, K, and L in a very similar manner. Taken together, these results clearly showed that CHX is a potent inhibitor of the cysteine cathepsins-proteolytic enzymes present in the dentin-pulp complex.
Fine and Gross Motor Task Performance When Using Computer-Based Video Models by Students With Autism and Moderate Intellectual Disability
Authors: Mechling Linda C. , Swindle Catherine O.
Published: January 2012

This investigation examined the effects of video modeling on the fine and gross motor task performance by three students with a diagnosis of moderate intellectual disability (Group 1) and by three students with a diagnosis of autism spectrum disorder (Group 2). Using a multiple probe design across three sets of tasks, the study examined the effectiveness of video modeling across differing types of motor response requirements (fine and gross motor) and whether effects would differ across disability groups. Results indicate an increase in the number of fine and gross motor tasks correctly performed following the introduction of video modeling. As a whole, students across both groups performed more gross motor than fine motor tasks independently correct and students in Group 1 performed more tasks independently correct than those in Group 2. Implications are discussed concerning evaluation of task requirements and the development of video models.
Chilean Adolescents’ and Parents’ Views on Autonomy Development
Authors: Martínez M. Loreto , Pérez J. Carola , Cumsille Patricio
Published: January 2012

This study aims to understand Chilean parents’ and adolescents’ conceptions of autonomy and whether they hold different expectations for autonomous behaviors by generation and socioeconomic level. A qualitative approach to data collection was used through separate focus groups of parents and adolescents from different socioeconomic condition. Substantial similarities in parents’ and adolescents’ conceptions of autonomy were found. Both generations conceive autonomy as multidimensional (i.e., self-sufficiency, decision making, and acting responsibly) and as an age-graded process that is achieved in interaction with parents. Participants emphasize the affective quality of the parent–adolescent relationship, particularly trust, for healthy autonomy achievement. Differences by socioeconomic status (SES) were also apparent in that low-middle-SES parents emphasize the self-sufficiency and responsibility component of autonomy, and adolescents grant more authority to parents in regulating adolescents’ behavior compared with their high-middle-SES counterparts
Examining the nature of resource-based processes in new venture development through a business-duality lens: A farming sector taxonomy
Authors: Perks Helen , Medway Dominic
Published: January 2012

This article investigates the nature of resource-based processes in the development of new ventures, adopting a business duality lens. Business duality occurs where a new venture is developed alongside an established business. The research employs a multiple case study methodology situated in the farming sector. The details of resource assembly and deployment are examined and presented through four stages of the entrepreneurial process: initiation, experimentation, mature and late stage. The findings offer insight into the manner in which resource ties between the businesses relate to processes of resource assembly and deployment and in addition, inform a business duality-based taxonomy. This depicting three generic approaches to managing resource-based processes in the development of new ventures in the farming sector: holistic innovators, reactive innovators and cautious innovators. We conclude by considering the implications of our arguments for new venture activity in other business duality contexts.
Abdominal Muscle Strains in Professional Baseball
Authors: Conte Stan A. , Thompson Matthew M. , Marks Matthew A. , Dines Joshua S.
Published: January 2012

Background: The abdominal core muscles (internal and external oblique, rectus and transversus abdominis) play an important role in the baseball activities of pitching and hitting. Proper abdominal muscle activation during throwing and swinging is crucial for generating optimal ball velocity and bat speed. Abdominal muscle strains can result in substantial loss of playing time, and their incidence has never been reported in baseball.

Hypothesis: The incidence of abdominal muscle strains in Major League Baseball has been rising over the past 20 years. Injuries contralateral to the dominant arm or batting side are more common and require more time to recover.

Study Design: Descriptive epidemiology study.

Methods: Abdominal muscle strains in baseball players were determined by retrospective review of the Major League Baseball disabled list from 1991 to 2010. Player age, position, dominant hand, batting side, and recovery time were recorded.

Results: There were 393 abdominal muscle strains in Major League Baseball from 1991 to 2010, constituting 5% of all baseball injuries. At least 92% of these injuries were internal/external oblique or intercostal muscle strains, and 44% of injuries were sustained by pitchers. The reinjury rate was 12.1%. An upward trend was seen from 1991 to 2010, especially in early-season injuries, and the overall injury rate was 22% higher in the 2000s than in the 1990s. Pitchers averaged 35.4 days on the disabled list compared with 26.7 days for position players ( P < .01); 78.1% of pitcher injuries were contralateral to their dominant arm, and 70.3% of position player injuries were contralateral to their dominant batting side (excluding switch hitters). Position players missed more time for contralateral than for ipsilateral injuries (28.9 vs 21.2 days, P = .03), whereas pitchers missed more time for ipsilateral injuries (44.5 vs 32.8 days, P = .04).

Conclusion: The incidence of abdominal muscle strains in baseball has been increasing over the past 20 years, especially early in the season, and there is a relatively high reinjury rate. This upward trend is in spite of new and more advanced diagnostic procedures, preventive core strengthening exercise programs, and rehabilitation techniques. Injuries contralateral to the dominant arm or batting side are more common.
Snowboarding Injuries
Authors: Kim Suezie , Endres Nathan K. , Johnson Robert J. , Ettlinger Carl F. , Shealy Jasper E.
Published: January 2012

Background: Participation in snowboarding as a winter sport is comparable to alpine skiing concerning the demographics of the participants, risk of injury, and variation in types of injuries sustained.

Purpose: To examine the types of snowboarding injuries and changes in injury patterns over time. We also sought to highlight important differences in injury patterns between snowboarders and alpine skiers as affected by age, experience, and sex.

Study Design: Case control; Level of evidence, 3.

Methods: Data were collected on injured snowboarders and skiers in a base-lodge clinic of a ski resort in Vermont over 18 seasons (1988-2006) and included extensive information about injury patterns, demographics, and experience. Control data were also obtained during this time period to provide information about the population at risk.

Results: The injury rates were assessed as mean days between injuries (MDBI). The average MDBI for all injuries among snowboarders was 345 as compared with 400 for skiers (the lower the number, the higher the injury rate). The most common type of injury for snowboarders was a wrist injury (MDBI, 1258), while for skiers, it was an anterior cruciate ligament (ACL) sprain (MDBI, 2332). Wrist injuries accounted for 27.6% of all snowboard injuries and 2.8% of skiing injuries, and ACL injuries composed 1.7% of all snowboard injuries and 17.2% of skiing injuries. Among snowboarders, more wrist injuries, shoulder soft tissue injuries, ankle injuries, concussions, and clavicle fractures were seen, while skiers had more ACL sprains, medial collateral ligament (MCL) sprains of the knee, lateral collateral ligament (LCL) sprains of the knee, lower extremity contusions, and tibia fractures. The trend analysis revealed an increased incidence of clavicle fractures ( P < .01) and a decrease in MCL injuries ( P < .01) and ankle injuries ( P < .025) among snowboarders over time. Skiers had a decrease in thumb metacarpophalangeal-ulnar collateral ligament (MCP-UCL) injuries ( P < .001) and MCL injuries of the knee ( P < .001) over time. We found the highest rate of injury among young, inexperienced, female snowboarders. When examining the location of injury, 21.8% of snowboard injuries occurred in the terrain park compared with 6.5% of ski injuries.

Conclusion: Injury rates in snowboarders have fluctuated over time but currently remain higher than in skiers. Wrist, shoulder, and ankle injuries are more common among snowboarders, while knee ligament injuries are more common in skiers. Injured snowboarders were significantly younger, less experienced, and more likely to be female than injured skiers or snowboard control participants. We did not find any evidence that those who spend time in terrain parks are overrepresented in the injury population.
The Incidence of Heterotopic Ossification After Hip Arthroscopy
Authors: Bedi Asheesh , Zbeda Robert M. , Bueno Vinicius F. , Downie Brian , Dolan Mark , Kelly Bryan T.
Published: January 2012

Background: Minimally invasive techniques to treat femoroacetabular impingement (FAI), snapping hip syndrome, and peritrochanteric space disorder (PSD) were developed to reduce complications and recovery time. Although a multitude of studies have reported on the incidence of heterotopic ossification (HO) after open procedures of the hip, there is little known about the rate of HO after hip arthroscopy.

Hypotheses: The incidence of HO after hip arthroscopy is comparable with that after open surgical dislocation of the hip and can be reduced with the addition of indomethacin to an existing nonsteroidal anti-inflammatory medication prophylaxis protocol.

Study Design: Cohort study; Level of evidence, 3.

Methods: Between July 2008 and July 2010, 616 primary hip arthroscopies were performed to treat FAI and PSD. In July 2009, indomethacin was added in the acute postoperative period to an existing HO prophylactic protocol of naproxen administered for 30 days postoperatively. Postoperative radiographs were reviewed to detect the presence and classify the size and location of HO. Odds ratios and logistic regression explored predictor variables and their relationships with HO, with P < .05 defined as significant.

Results: Twenty-nine (21 male, 8 female) of 616 (4.7%) hip procedures developed HO postoperatively. Brooker classification of HO was 18 grade I, 4 grade II, 6 grade III, and 1 grade IV. Mean follow-up was 13.2 months (range, 2.9-26.5 months). Rate of HO for cases with and without indomethacin for prophylaxis was 1.8% (6/339) and 8.3% (23/277), respectively. This difference was statistically significant ( P < .05), and patients who underwent protocol 1 were 4.36 times more likely to develop HO postoperatively than those who had protocol 2. The majority of cases of HO (72.4%) occurred in male patients, and all cases occurred in the setting of osteoplasty performed for symptomatic FAI. We were not able to demonstrate statistically significant clinical risk factors that were predictive for the development of postoperative HO. However, the data clearly demonstrate that the performance of arthroscopic osteoplasty with a capsular cut in male patients represented the majority of cases, who are likely the group at highest risk. Seven cases (~1%) required revision procedures to excise HO. There were no cases of recurrence of HO after excision, whether it was performed open or arthroscopically.

Conclusion: The addition of indomethacin is effective in reducing the incidence of HO after hip arthroscopy and should be especially considered in male patients who undergo osteoplasty for correction of symptomatic FAI.
Sports Activity After Osteochondral Transplantation of the Talus
Authors: Paul Jochen , Sagstetter Michael , Lämmle Lena , Spang Jeffrey , El-Azab Hosam , Imhoff Andreas B. , Hinterwimmer Stefan
Published: January 2012

Background: There are limited data regarding activity after osteochondral transplantation of the talus in orthopaedic publications.

Hypothesis: Osteochondral transplantation of the talus is a clinically successful treatment and enables patients to pursue regular and ongoing recreational sporting activities.

Study Design: Case series; Level of evidence, 4.

Methods: One hundred thirty-one patients were retrospectively analyzed to determine their sporting and recreational activities at an average of 60 ± 28.4 months postoperatively (range, 24-141 months). The clinical evaluation included the Tegner activity scale, the Activity Rating Scale (ARS), and a visual analog scale (VAS) for pain.

Results: The VAS illustrated significant preoperative to postoperative improvements (6.3 to 2.7; P < .001). Regarding sporting activity, 96.9% of the patients were engaged in sports during their lifetimes compared with 83.8% the year before surgery and 89.3% at the time of survey. The Tegner score dropped from 5.9 preoperatively to 5.0 after surgery ( P = .001), and the ARS decreased from 8.9 preoperatively to 6.8 postoperatively ( P = .003). The sports frequency and the duration of activities did not significantly change after surgery: 1.7 ± 2.0 (range, 0-8; P = .053) and 4.2 ± 3.8 hours (range, 0-30 hours; P = .052), respectively. The number of actual reported different sports disciplines was unchanged in comparison to the year before surgery (3.7 ± 2.9; range, 0-12). The top 10 cited sports activities did not change for the lifetime, preoperative, and postoperative periods but illustrated an altered order. Although the overall satisfaction with the surgery was good, 15% of our patients were only partially satisfied, and 14% were not satisfied with the procedure.

Conclusion: Patients engage in fewer, less frequent sporting activities when a symptomatic osteochondral lesion (OCL) at the talus is present. Talar osteochondral transplantation shows good clinical midterm results and allows patients to return to sporting activity. However, we found patients modify their postoperative sporting activities, and we noted a reduction of participation in high-impact and contact sports.
Immigrant Organizations in Pursuit of Inclusive Planning
Authors: Kondo Michelle C.
Published: January 2012

This article highlights a case in which an immigrant organization, called the Trusted Advocates, brokered for the inclusion of immigrant interests in a neighborhood annexation decision. Racialized controversies over neighborhood identity, and planners’ and officials’ distrust of the organization, provided two main challenges to the organization’s efficacy. The analysis reveals that while immigrant organizations need to provide evidence of their accountability, planning processes in diverse contexts can benefit from their cultural fluency, social capital, and innovative ideas for engagement. Efforts on the part of planners and immigrant organizations to build mutual trust may facilitate the development of negotiated visions for neighborhoods’ future.
Making Local Planning Work for Urban Agriculture in the North American Context
Authors: Thibert Joël
Published: January 2012

A small but growing literature is investigating the benefits of urban agriculture (UA) in North America, but there has been little analysis of the practical planning and policy implications of these practices. A review of the recent literature and an analysis of UA in Detroit, Toronto, and Montreal based on interviews with practitioners and other actors suggest that UA practices vary significantly and face cultural as well as legal and technical challenges. These findings support the view that UA belongs within planning and that municipalities have an important role to play in facilitating its development.
Design and biomechanical testing of pedicle screw for osteoporotic incidents
Authors: Demir Teyfik , Camuşcu Necip , Türeyen Kudret
Published: January 2012

In this study, geometrical features of pedicle screws have been modified and their performances are compared. Performance analysis has been made in terms of pull-out strength and torsional strength. The parameters investigated are core diameter, holes drilled normal to screw axis, angle between sequential holes and distance between holes. Three different core diameter have been studied, which are 4 mm (normal core diameter), 5 mm (medium core diameter) and 5.5 mm (high core diameter). Distance between sequential holes has been arranged such that there is either one hole per pitch or one hole per two pitches. Angle between sequential holes is either 90° or 120°. According to the test results, the screw, with medium core diameter (5 mm) containing one hole per two pitches with 90° angle between sequential holes, has exhibited the optimum performance considering torsional strength and pull-out strength requirements. Its torsional strength is slightly higher than and, when Grade 40 polyurethane foam was used as bone simulating material, its pull-out strength is as good as, an undrilled normal core diameter screw, which is already being used in surgical operations. The fatigue performance of this best performed screw has also been found satisfactory according to the related standard. Its pull-out strength is also tested on a calf vertebra and a promising result has been obtained.