bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperglycemia Inhibits Complement-Mediated Immunological Control ofS. aureusin a Rat Model of Peritonitis
Authors: Mauriello Clifford T. , Hair Pamela S. , Rohn Reuben D. , Rister Nicholas S. , Krishna Neel K. , Cunnion Kenji M.
Published: December 2014

Hyperglycemia from diabetes is associated with increased risk of infection fromS. aureusand increased severity of illness. Previous work in our laboratory demonstrated that elevated glucose (>6 mM) dramatically inhibitedS. aureus-initiated complement-mediated immune effectors. Here we reportin vivostudies evaluating the extent to which a hyperglycemic environment alters complement-mediated control ofS. aureusinfection in a rat peritonitis model. Rats were treated with streptozocin to induce diabetes or sham-treated and then inoculated i.p. withS. aureus. Rats were euthanized and had peritoneal lavage at 2 or 24 hours after infection to evaluate early and late complement-mediated effects. Hyperglycemia decreased the influx of IgG and complement components into the peritoneum in response toS. aureusinfection and decreased anaphylatoxin generation. Hyperglycemia decreased C4-fragment and C3-fragment opsonization ofS. aureusrecovered in peritoneal fluids, compared with euglycemic or insulin-rescued rats. Hyperglycemic rats showed decreased phagocytosis efficiency compared with euglycemic rats, which correlated inversely with bacterial survival. These results suggest that hyperglycemia inhibited humoral effector recruitment, anaphylatoxin generation, and complement-mediated opsonization ofS. aureus, suggesting that hyperglycemic inhibition of complement effectors may contribute to the increased risk and severity ofS. aureusinfections in diabetic patients.
The Combined Extract of Purple Waxy Corn and Ginger Prevents Cataractogenesis and Retinopathy in Streptozotocin-Diabetic Rats
Authors: Thiraphatthanavong Paphaphat , Wattanathorn Jintanaporn , Muchimapura Supaporn , Thukham-mee Wipawee , Lertrat Kamol , Suriharn Bhalang
Published: December 2014

Based on the crucial roles of oxidative stress and aldose reductase on diabetic complications and the protective effect against diabetic eye complication of purple waxy corn and ginger (PWCG) together with the synergistic effect concept, we aimed to determine anticataract and antiretinopathy effects of the combined extract of purple waxy corn and ginger (PWCG). The streptozotocin diabetics with the blood glucose levels >250 mg·dL−1were orally given the extract at doses of 50, 100, and 200 mg/kg·BW−1for 10 weeks. Then, lens opacity and histopathology of retina were determined. The changes of MDA together with the activities of SOD, CAT, GPx, and AR in lens were also determined using biochemical assays. All doses of PWCG decreased lens opacity, MDA, and AR in the lens of diabetic rats. The elevation of CAT and GPx activities was also observed. The antiretinopathy property of the combined extract was also confirmed by the increased number of neurons in ganglion cell layer and thickness of total retina and retinal nuclear layer in diabetic rats. PWCG is the potential functional food to protect against diabetic cataract and retinopathy. However, further studies concerning toxicity and clinical trial are still essential.
Hyperglycemia Induces Toll-Like Receptor-2 and -4 Expression and Activity in Human Microvascular Retinal Endothelial Cells: Implications for Diabetic Retinopathy
Authors: Rajamani Uthra , Jialal Ishwarlal
Published: December 2014

Diabetic retinopathy (DR) causes visual impairment in working age adults and hyperglycemia-mediated inflammation is central in DR. Toll-like receptors (TLRs) play a key role in innate immune responses and inflammation. However, scanty data is available on their role in DR. Hence, in this study, we examined TLR2 and TLR4 mRNA and protein expression and activity in hyperglycemic human retinal endothelial cells (HMVRECs). HMVRECs were treated with hyperglycemia (HG) or euglycemia and mRNA and protein levels of TLR-2, TLR-4, MyD88, IRF3, and TRIF as well as NF-κB p65 activation were measured. IL-8, IL-1β, TNF-αand MCP-1, ICAM-1, and VCAM-1 as well as monocyte adhesion to HMVRECs were also assayed. HG (25 mM) significantly induced TLR2 and TLR4 mRNA and protein in HMVRECs. It also increased both MyD88 and non-MyD88 pathways, nuclear factor-κB (NF-κB), biomediators, and monocyte adhesion. This inflammation was attenuated by TLR-4 or TLR-2 inhibition, and dual inhibition by a TLR inhibitory peptide as well as TLR2 and 4 siRNA. Additionally, antioxidant treatment reduced TLR-2 and TLR4 expression and downstream inflammatory markers. Collectively, our novel data suggest that hyperglycemia induces TLR-2 and TLR-4 activation and downstream signaling mediating increased inflammation possibly via reactive oxygen species (ROS) and could contribute to DR.
Palmprint Authentication System Based on Local and Global Feature Fusion Using DOST
Authors: Kumar N. B. Mahesh , Premalatha K.
Published: December 2014

Palmprint is the region between wrist and fingers. In this paper, a palmprint personal identification system is proposed based on the local and global information fusion. The local and global information is critical for the image observation based on the results of the relationship between physical stimuli and perceptions. The local features of the enhanced palmprint are extracted using discrete orthonormal Stockwell transform. The global feature is obtained by reducing the scale of discrete orthonormal Stockwell transform to infinity. The local and global matching distances of the two palmprint images are fused to get the final matching distance of the proposed scheme. The results show that the fusion of local and global features outperforms the existing works on the available three datasets.
A Comparative Study of Bioartificial Bone Tissue Poly‐L‐lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration
Authors: Weng Weizong , Song Shaojun , Cao Liehu , Chen Xiao , Cai Yuanqi , Li Haihang , Zhou Qirong , Zhang Jun , Su Jiacan
Published: December 2014

Bioartificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly‐L‐lactic acid/polycaprolactone) by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with PLLA scaffold), group B (repaired with PLLA/PCL scaffold), and group C (no scaffold) to evaluate the bone‐remodeling ability of the implants. Micro‐CT examination revealed the prime bone regeneration ability of group B in three groups. Bone mineral density of surgical site in group B was higher than group A but lower than group C. Meanwhile, the bone regeneration in both groups A and B proceeded with signs of inflammation for the initial fast degradation of scaffolds. As a whole, PLLA/PCL scaffolds in vivo initially degrade fast and were better suited to repair bone defect than PLLA in New Zealand rabbits. Furthermore, for the low mineral density of new bone and rapid degradation of the scaffolds, more researches were necessary to optimize the composite for bone regeneration.
Use of the Composite Pedicled Pectoralis Minor Flap after Resection of Soft Tissue Sarcoma in Reconstruction of the Glenohumeral Joint
Authors: van de Sande Michiel A. J. , Cosker Tom , McDonnell Stephen M. , Gibbons C. L. M. H. , Giele Henk
Published: December 2014

The surgical repair of an extensive anterior glenohumeral soft tissue defect is complicated by glenohumeral instability and subsequent significant functional deficit. This surgical note offers a relatively simple reconstruction of the anterior capsule and subscapularis muscle using a pectoralis minor pedicle flap. This reconstruction is supplemented with functional reconstruction of the anterior glenohumeral joint. A conventional deltopectoral approach is utilized and pectoralis minor is freed from its coracoid insertion, released, and mobilized without compromising the pedicle entering from the dorsum and inferior one-third of the muscle. The mobilized pectoralis minor vascular pedicle has sufficient length for the pectoralis minor to be transferred to provide coverage of the anterior shoulder joint even in full external rotation, providing anterior stability. To further improve glenohumeral stability and shoulder function, the pectoralis major muscle can be split with the clavicular part reinserted lateral to the bicipital groove onto the lesser tuberosity replacing subscapularis function while stabilising the glenohumeral joint.
Acupuncture Alleviated the Nonmotor Symptoms of Parkinson’s Disease including Pain, Depression, and Autonomic Symptoms
Authors: Iseki Chifumi , Furuta Taiga , Suzuki Masao , Koyama Shingo , Suzuki Keiji , Suzuki Tomoko , Kaneko Akiyo , Mitsuma Tadamichi
Published: December 2014

A woman started to feel intractable pain on her lower legs when she was 76. At the age of 78, she was diagnosed as having Parkinson’s disease (PD). The leg pain was suspected to be a symptom of PD after eliminating other causes. The patient also suffered from nonmotor symptoms, depression, anxiety, hot flashes, and paroxysmal sweating. Though the patient had received pharmacotherapy including levodopa for 5 years, she still suffered from the nonmotor symptoms and was referred to our department. We treated her with acupuncture based on the Chinese traditional medicine and electroacupuncture five times per week. After the 2-week treatment, the assessment for the symptoms was as follows; visual analogue scale (VAS) score of the leg pain was 16 mm (70 mm, before), Hamilton’s rating scales for depression (HAM-D) score was 9 (18, before), timed 3 m Up and Go took 20 steps in 30 sec (24 steps in 38 sec, before), and the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 1 score was 13 (21, before). Autonomic symptoms, hot flashes and paroxysmal sweating, were also alleviated. Acupuncture may be a good treatment modality for nonmotor symptoms in PD.
Immobilization ofAspergillus nigerF7-02 Lipase in Polysaccharide Hydrogel Beads ofIrvingia gabonensisMatrix
Authors: Kareem Safaradeen Olateju , Adio Olayinka Quadri , Osho Michael Bamitale
Published: December 2014

The potential of polysaccharideIrvingia gabonensismatrix as enzyme immobilization support was investigated. Lipase ofAspergillus nigerF7-02 was immobilized by entrapment using glutaraldehyde as the cross-linking agent and stabilized in ethanolic-formaldehyde solution. The pH and temperature stability and activity yield of the immobilized enzyme were determined. Such parameters as enzyme load, bead size, number of beads, and bead reusability were also optimized. Adequate gel strength to form stabilized beads was achieved at 15.52% (w/v)Irvingia gabonensispowder, 15% (v/v) partially purified lipase, 2.5% (v/v) glutaraldehyde, and 3 : 1 (v/v) ethanolic-formaldehyde solution. There was 3.93-fold purification when the crude enzyme was partially purified in two-step purification using Imarsil and activated charcoal. Optimum lipase activity 75.3 Ug−1was achieved in 50 mL test solution containing 15 beads of 7 mm bead size. Relative activity 80% was retained at eight repeated cycles. The immobilization process gave activity yield of 59.1% with specific activity of 12.3 Umg−1and stabilized at optimum pH 4.5 and temperature 55°C. Thus the effectiveness and cost-efficiency ofI. gabonensisas a polymer matrix for lipase immobilization have been established.
Preoxidation and Activation of the Lignin Char: Carbonization and Oxidation Procedures
Authors: Sebbahi Saloua , Ahmido Adnane , Kifani-Sahban Fatima , El Hajjaji Souad , Zoulalian André
Published: December 2014

A comprehensive process of pretreatment and oxidation of lignin char was developed to optimize the production of activated carbon. The lignin char was obtained by carbonization of lignin under nitrogen at 600°C for 2 hours. The optimum time and temperature used to oxidize the char without destruction were, respectively, 6 hours and 245°C. The oxygen improves the reactivity of the sample in CO2and evolved the sample of a thermoplastic behaviour to a thermosetting behaviour. The oxygenation in air of the lignin char does not change the mode of deformation acquired by the material during the carbonization. The preoxidized coal reacts more than the nonoxidized coal during the CO2activation, whereas the reduction in volume in the first case is smaller than in the second. The preoxidized and then activated carbon shows the formation and the development of microporosity at the expense of macroporosity. This microstructure is one of the main characteristics of activated carbon, which can be used as adsorbent for different pollutants.
Re-Evaluation of the Anticoagulant Properties of High-Density Lipoprotein—Brief Report
Authors: Fernandez Jose A. , Deguchi Hiroshi , Banka Carole L. , Witztum Joseph L. , Griffin John H.
Published: December 2014

Objective—

This study was conducted to resolve the striking controversy between our previous report that high-density lipoprotein (HDL) enhances activated protein C (APC)/protein S anticoagulant actions and a subsequent, contradicting report that HDL lacks this activity.

Approach and Results—

When fresh HDL preparations from 2 laboratories were subjected to Superose 6 column chromatography, fractions containing HDL-enhanced APC:protein S anticoagulant actions in clotting assays, thereby validating our previous report. Moreover, the ability of HDL to enhance the anticoagulant actions of APC:protein S was neutralized by anti-apoAI antibodies, further indicating that the activity is because of HDL particles and not because of contaminating phospholipid vesicles. Density gradient subfractionation studies of HDL showed that large HDL subfractions (densities between 1.063 and 1.125 g/mL) contained the APC:protein S–enhancing activity. Fresh HDL stored at 4°C gradually lost its anticoagulant enhancing activity for 14 days, indicating moderate instability in this activity of purified HDL.

Conclusions—

These studies conclusively demonstrate that freshly prepared HDL fractions possess anticoagulant activity. Fractions from Superose 6 columns that contain HDL reproducibly enhance APC:protein S anticoagulant activity, consistent with the hypothesis that HDL has antithrombotic activity and with the observation that low HDL levels are found in male venous thrombosis patients. Understanding the basis for this activity could lead to novel therapeutic approaches to regulate venous thrombosis.
Extracellular Cyclophilin A Activates Platelets Via EMMPRIN (CD147) and PI3K/Akt Signaling, Which Promotes Platelet Adhesion and Thrombus Formation In Vitro and In Vivo
Authors: Seizer Peter , Ungern-Sternberg Saskia N.I.v. , Schönberger Tanja , Borst Oliver , Münzer Patrick , Schmidt Eva-Maria , Mack Andreas F. , Heinzmann David , Chatterjee Madhumita , Langer Harald , Malešević Miroslav , Lang Florian , Gawaz Meinrad , Fischer Gunter , May Andreas E.
Published: December 2014

Objective—

Cyclophilin A (CyPA) is secreted under inflammatory conditions by various cell types. Whereas the important role of intracellular CyPA for platelet function has been reported, the effect of extracellular CyPA on platelet function has not been investigated yet.

Approach and Results—

Inhibition of extracellular CyPA through a novel specific inhibitor MM284 reduced thrombus after ferric chloride–induced injury in vivo. In vitro extracellular CyPA enhanced thrombus formation even in CyPA
−/−
platelets. Treatment of isolated platelets with recombinant CyPA resulted in platelet degranulation in a time- and dose-dependent manner. Inhibition of the platelet surface receptor extracellular matrix metalloproteinase inducer (cluster of differentiation 147) by an anticluster of differentiation 147 monoclonal antibody significantly reduced CyPA-dependent platelet degranulation. Pretreatment of platelets with CyPA enhanced their recruitment to mouse carotid arteries after arterial injury, which could be inhibited by an anticluster of differentiation 147 monoclonal antibody (intravital microscopy). The role of extracellular CyPA in adhesion could be confirmed by infusing CyPA
−/−
platelets in CyPA
+/+
mice and by infusing CyPA
+/+
platelets in CyPA
−/−
mice. Stimulation of platelets with CyPA induced phosphorylation of Akt, which could in turn be inhibited in the presence of phosphoinositid-3-kinase inhibitors. Akt-1
−/−
platelets revealed a markedly decreased degranulation on CyPA stimulation. Finally, ADP-induced platelet aggregation was attenuated by MM284, as well as by inhibiting paracrine-secreted CyPA without directly affecting Ca
2+
-signaling.

Conclusions—

Extracellular CyPA activates platelets via cluster of differentiation 147–mediated phosphoinositid-3-kinase/Akt-signaling, leading to enhanced adhesion and thrombus formation independently of intracellular CyPA. Targeting extracellular CyPA via a specific inhibitor may be a promising strategy for platelet inhibition without affecting critical functions of intracellular CyPA.
Central Cardiac Limit to Aerobic Capacity in Patients With Exertional Pulmonary Venous Hypertension
Authors: Santos Mário , Opotowsky Alexander R. , Shah Amil M. , Tracy Julie , Waxman Aaron B. , Systrom David M.
Published: December 2014

Background—

The mechanism of functional limitation in heart failure with preserved ejection fraction remains controversial. We examined the contributions of central cardiac and peripheral mechanisms and hypothesized that the pulmonary vascular response to exercise is an important determinant of aerobic capacity among patients with exertional pulmonary venous hypertension (ePVH).

Methods and Results—

We compared 31 ePVH patients (peak V
O
2
<80% of predicted and peak pulmonary arterial wedge pressure≥20 mm Hg) with 31 age- and sex-matched controls (peak V
O
2
>80% predicted) who underwent invasive cardiopulmonary exercise testing for unexplained exertional intolerance. ePVH patients had lower peak cardiac output (73±14% versus 103±18% predicted;
P
<0.001) compared with controls, related both to impaired chronotropic response (peak heart rate 111±25 beats per minute versus 136±24 beats per minute;
P
<0.001) and to reduced peak stroke volume index (47±10 mL/min per m
2
versus 54±15 mL/min per m
2
;
P
=0.03). Peak systemic O
2
extraction was not different between groups (arterial-mixed venous oxygen content difference: 13.0±2.1 mL/dL versus 13.4±2.4 mL/dL;
P
=0.46). ePVH patients had higher resting (150±74 versus 106±50 dyne/s per cm
−5
;
P
=0.009), peak (124±74 dyne/s per cm
−5
versus 70±41 dyne/s per cm
−5
;
P
<0.001), and isoflow pulmonary vascular resistance (124±74 dyne/s per cm
−5
versus 91±33 dyne/s per cm
−5
at cardiac output≈10.6 L/min;
P
=0.04). Pulmonary vascular resistance decreased with exercise in all control subjects but increased in 36% (n=11) of ePVH patients. Abnormal pulmonary vascular response was not associated with peak V
O
2
.

Conclusions—

Reduced cardiac output response, rather than impaired peripheral O
2
extraction, constrains oxygen delivery and aerobic capacity in ePVH. Pulmonary vascular dysfunction is common in patients with ePVH at rest and during exercise.
Ventricular Conduction and Long-Term Heart Failure Outcomes and Mortality in African Americans
Authors: Mentz Robert J. , Greiner Melissa A. , DeVore Adam D. , Dunlay Shannon M. , Choudhary Gaurav , Ahmad Tariq , Khazanie Prateeti , Randolph Tiffany C. , Griswold Michael E. , Eapen Zubin J. , O’Brien Emily C. , Thomas Kevin L. , Curtis Lesley H. , Hernandez Adrian F.
Published: December 2014

Background—

QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans.

Methods and Results—

We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0–14.4) versus 7.1% (95% CI, 6.3–8.0) and 8.2% (95% CI, 6.9–9.7) versus 4.4% (95% CI, 3.7–5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03–1.56;
P
=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01–1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation.

Conclusions—

QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.
Effect of Physical Activity on Age-Related Changes in Cardiac Function and Performance in Women
Authors: Jakovljevic Djordje G. , Papakonstantinou Lida , Blamire Andrew M. , MacGowan Guy A. , Taylor Roy , Hollingsworth Kieren G. , Trenell Michael I.
Published: December 2014

Background—

Higher levels of physical activity are associated with reduced cardiovascular mortality but its effect on age-related changes in cardiac structure and function is unknown. The present study defines the effect of daily physical activity on age-related changes in cardiac structure, function, metabolism, and performance in healthy women.

Methods and Results—

Sixty-three healthy women were grouped according to age (young, 20–30 years, n=21; middle, 40–50 years, n=22; and older, 65–81 years, n=20) and daily physical activity level (low active <7500 and high active >12 500 steps/d). Participants underwent cardiac MRI including tissue tagging and
31
P spectroscopy and exercise testing with noninvasive central hemodynamic measurements. Aging was associated with increased concentric remodeling (
P
<0.01) and left ventricular torsion (
P
<0.01), and a decline in diastolic function (
P
<0.01), cardiac phosphocreatine:ATP ratio (
P
<0.01), peak exercise cardiac power output (
P
<0.01), and O
2
consumption (
P
<0.01). Older high-active women demonstrated a phosphocreatine:ATP ratio and relative peak O
2
consumption similar to young low-active women, and 23% and 26% higher than older low-active women (phosphocreatine:ATP ratio, 1.9±0.2 versus 1.4±0.1;
P
<0.05 and O
2
consumption, 24.1±3.8 versus 17.8±2.0 mL/[kg·min];
P
<0.01). In older women, physical activity had no effect on eccentricity ratio (0.9±0.2 versus 0.8±0.1 g/mL;
P
=0.19), E/A ratio (1.3±0.5 versus 1.4±0.5;
P
=0.66), torsion (7.6±1.7 versus 8.0°±2.1°;
P
=0.20), and peak cardiac power output (3.4±0.7 versus 3.4±0.8 W;
P
=0.91).

Conclusions—

A higher level of daily physical activity preserves cardiac metabolism and exercise capacity with aging but has limited effect on age-related changes in concentric remodeling, diastolic function, and cardiac performance.
Reproducibility in Science
Authors: Begley C. Glenn , Ioannidis John P.A.
Published: December 2014

Medical and scientific advances are predicated on new knowledge that is robust and reliable and that serves as a solid foundation on which further advances can be built. In biomedical research, we are in the midst of a revolution with the generation of new data and scientific publications at a previously unprecedented rate. However, unfortunately, there is compelling evidence that the majority of these discoveries will not stand the test of time. To a large extent, this reproducibility crisis in basic and preclinical research may be as a result of failure to adhere to good scientific practice and the desperation to publish or perish. This is a multifaceted, multistakeholder problem. No single party is solely responsible, and no single solution will suffice. Here we review the reproducibility problems in basic and preclinical biomedical research, highlight some of the complexities, and discuss potential solutions that may help improve research quality and reproducibility.
Role of Mineralocorticoid Receptor Antagonists in Cardiovascular Disease
Authors: Ferrario Carlos M. , Schiffrin Ernesto L.
Published: December 2014

Aldosterone exerts its best known sodium homeostasis actions by controlling sodium excretion at the level of the distal tubules via activation of the apical epithelial sodium channel and the basolateral Na
+
/K
+
ATPase pump. Recently, this mineralocorticoid hormone has been demonstrated to act on the heart and blood vessels. Excess release of aldosterone in relation to the salt status induces both genomic and nongenomic effects that by promoting endothelial dysfunction, and vascular and cardiorenal adverse remodeling, contribute to the target organ damage found in hypertension, heart failure, myocardial infarction, and chronic renal failure. Mineralocorticoid receptor blockers have been shown to be highly effective in resistant hypertension and to slow down heart failure progression, and in experimental animals, the development of atherosclerosis. Blockade of the action of aldosterone and potentially other mineralocorticoid steroids has been increasingly demonstrated to be an extremely beneficial therapy in different forms of cardiovascular disease. This review provides a summary of the knowledge that exists on aldosterone actions in the cardiovascular system and, in providing the translational impact of this knowledge to the clinical arena, illustrates how much more needs to be achieved in exploring the use of mineralocorticoid receptor blockers in less advanced stages of heart, renal, and vascular disease.
Role for Telomerase in Pulmonary Hypertension
Authors: Mouraret Nathalie , Houssaïni Amal , Abid Shariq , Quarck Rozenn , Marcos Elisabeth , Parpaleix Aurelien , Gary-Bobo Guillaume , Dubois-Randé Jean-Luc , Derumeaux Geneviève , Boczkowski Jorge , Delcroix Marion , Blasco Maria A. , Lipskaia Larissa , Amsellem Valérie , Adnot Serge
Published: December 2014

Background—

Cells exhibiting dysregulated growth may express telomerase reverse transcriptase (TERT), the dual function of which consists of maintaining telomere length, in association with the RNA template molecule TERC, and controlling cell growth. Here, we investigated lung TERT in human and experimental pulmonary hypertension (PH) and its role in controlling pulmonary artery smooth muscle cell (PA-SMC) proliferation.

Methods and Results—

Marked TERT expression or activity was found in lungs from patients with idiopathic PH and from mice with PH induced by hypoxia or serotonin-transporter overexpression (SM22-5HTT
+
mice), chiefly within PA-SMCs. In cultured mouse PA-SMCs, TERT was expressed on growth stimulation by serum. The TERT inhibitor imetelstat and the TERT activator TA65 abrogated and stimulated PA-SMC growth, respectively. PA-SMCs from PH mice showed a heightened proliferative phenotype associated with increased TERT expression, which was suppressed by imetelstat treatment. TERC
−/−
mice at generation 2 and TERT
−/−
mice at generations 2, 3, and 4 developed less severe PH than did wild-type mice exposed to chronic hypoxia, with less distal pulmonary artery muscularization and fewer Ki67-stained proliferating PA-SMCs. Telomere length differed between TERC
−/−
and TERT
−/−
mice, whereas PH severity was similar in the 2 strains and across generations. Chronic imetelstat treatment reduced hypoxia-induced PH in wild-type mice or partially reversed established PH in SM22-5HTT
+
mice while simultaneously decreasing TERT expression. Opposite effects occurred in mice treated with TA65.

Conclusions—

Telomerase exerts telomere-independent effects on PA-SMC growth in PH and may constitute a treatment target for PH.
Oxidative Stress Activates Endothelial Innate Immunity via Sterol Regulatory Element Binding Protein 2 (SREBP2) Transactivation of MicroRNA-92a
Authors: Chen Zhen , Wen Liang , Martin Marcy , Hsu Chien-Yi , Fang Longhou , Lin Feng-Mao , Lin Ting-Yang , Geary McKenna J. , Geary Greg G. , Zhao Yongli , Johnson David A. , Chen Jaw-Wen , Lin Shing-Jong , Chien Shu , Huang Hsien-Da , Miller Yury I. , Huang Po-Hsun , Shyy John Y-J.
Published: December 2014

Background—

Oxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase–derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element–binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium.

Methods and Results—

Using cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II–infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell–specific SREBP2 transgenic mice, locked nucleic acid–modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II–induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell–dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1β.

Conclusions—

Our findings suggest that SREBP2–miR-92a–inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.
Genetic Architecture of White Matter Hyperintensities Differs in Hypertensive and Nonhypertensive Ischemic Stroke
Authors: Adib-Samii Poneh , Devan William , Traylor Matthew , Lanfranconi Silvia , Zhang Cathy R. , Cloonan Lisa , Falcone Guido J. , Radmanesh Farid , Fitzpatrick Kaitlin , Kanakis Allison , Rothwell Peter M. , Sudlow Cathie , Boncoraglio Giorgio B. , Meschia James F. , Levi Chris , Dichgans Martin , Bevan Steve , Rosand Jonathan , Rost Natalia S. , Markus Hugh S.
Published: December 2014

Background and Purpose—

Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [
H
SNP
]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals.

Methods—

WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate
H
SNP
for WMHV overall and within subgroups stratified by risk factors found to be significant in multivariate analyses.

Results—

A significant proportion of the variance of WMHV was attributable to common SNPs after adjustment for significant risk factors (
H
SNP
=0.23;
P
=0.0026).
H
SNP
estimates were higher among hypertensive individuals (
H
SNP
=0.45;
P
=7.99×10
−5
); this increase was greater than expected by chance (
P
=0.012). In contrast, estimates were lower, and nonsignificant, in nonhypertensive individuals (
H
SNP
=0.13;
P
=0.13).

Conclusions—

A quarter of variance is attributable to common SNPs, but this estimate was greater in hypertensive individuals. These findings suggest that the genetic architecture of WMH in ischemic stroke differs between hypertensives and nonhypertensives. Future WMHV GWAS studies may gain power by accounting for this interaction.
Variations in Acute Hospital Stroke Care and Factors Influencing Adherence to Quality Indicators in 6 European Audits
Authors: Wiedmann Silke , Hillmann Steffi , Abilleira Sònia , Dennis Martin , Hermanek Peter , Niewada Maciej , Norrving Bo , Asplund Kjell , Rudd Anthony G. , Wolfe Charles D.A. , Heuschmann Peter U.
Published: December 2014

Background and Purpose—

We compared compliance with standards of acute stroke care between 6 European audits and identified factors associated with delivery of appropriate care.

Methods—

Data were derived from stroke audits in Germany, Poland, Scotland, Catalonia, Sweden, and England/Wales/Northern-Ireland participating within the European Implementation Score (EIS) collaboration. Associations between demographic and clinical characteristics with adherence to predefined quality indicators were investigated by hierarchical logistic regression analyses.

Results—

In 2007/2008 data from 329 122 patients with stroke were documented. Substantial variations in adherence to quality indicators were found; older age was associated with a lower probability of receiving thrombolytic therapy, anticoagulant therapy, or stroke unit treatment and a higher probability of being tested for dysphagia. Women were less likely to receive anticoagulant or antiplatelet therapy or stroke unit treatment. No major weekend effect was found.

Conclusions—

Detected variations in performance of acute stroke services were found. Differences in adherence to quality indicators might indicate population subgroups with specific needs for improving care delivery.
Hypertension Treatment Intensification Among Stroke Survivors With Uncontrolled Blood Pressure
Authors: Roumie Christianne L. , Zillich Alan J. , Bravata Dawn M. , Jaynes Heather A. , Myers Laura J. , Yoder Joseph , Cheng Eric M.
Published: December 2014

Background and Purpose—

We examined blood pressure 1 year after stroke discharge and its association with treatment intensification.

Methods—

We examined the systolic blood pressure (SBP) stratified by discharge SBP (≤140, 141–160, or >160 mm Hg) among a national cohort of Veterans discharged after acute ischemic stroke. Hypertension treatment opportunities were defined as outpatient SBP >160 mm Hg or repeated SBPs >140 mm Hg. Treatment intensification was defined as the proportion of treatment opportunities with antihypertensive changes (range, 0%–100%, where 100% indicates that each elevated SBP always resulted in medication change).

Results—

Among 3153 patients with ischemic stroke, 38% had ≥1 elevated outpatient SBP eligible for treatment intensification in the 1 year after stroke. Thirty percent of patients had a discharge SBP ≤140 mm Hg, and an average 1.93 treatment opportunities and treatment intensification occurred in 58% of eligible visits. Forty-seven percent of patients discharged with SBP 141 to160 mm Hg had an average of 2.1 opportunities for intensification and treatment intensification occurred in 60% of visits. Sixty-three percent of the patients discharged with an SBP >160 mm Hg had an average of 2.4 intensification opportunities, and treatment intensification occurred in 65% of visits.

Conclusions—

Patients with discharge SBP >160 mm Hg had numerous opportunities to improve hypertension control. Secondary stroke prevention efforts should focus on initiation and review of antihypertensives before acute stroke discharge; management of antihypertensives and titration; and patient medication adherence counseling.
Characterizing Congo Basin Rainfall and Climate Using Tropical Rainfall Measuring Mission (TRMM) Satellite Data and Limited Rain Gauge Ground Observations
Authors: Munzimi Yolande A. , Hansen Matthew C. , Adusei Bernard , Senay Gabriel B.
Published: December 2014

Quantitative understanding of Congo River basin hydrological behavior is poor because of the basin’s limited hydrometeorological observation network. In cases such as the Congo basin where ground data are scarce, satellite-based estimates of rainfall, such as those from the joint NASA/JAXA Tropical Rainfall Measuring Mission (TRMM), can be used to quantify rainfall patterns. This study tests and reports the use of limited rainfall gauge data within the Democratic Republic of Congo (DRC) to recalibrate a TRMM science product (TRMM 3B42, version 6) in characterizing precipitation and climate in the Congo basin. Rainfall estimates from TRMM 3B42, version 6, are compared and adjusted using ground precipitation data from 12 DRC meteorological stations from 1998 to 2007. Adjustment is achieved on a monthly scale by using a regression-tree algorithm. The output is a new, basin-specific estimate of monthly and annual rainfall and climate types across the Congo basin. This new product and the latest version-7 TRMM 3B43 science product are validated by using an independent long-term dataset of historical isohyets. Standard errors of the estimate, root-mean-square errors, and regression coefficients r were slightly and uniformly better with the recalibration from this study when compared with the 3B43 product (mean monthly standard errors of 31 and 40 mm of precipitation and mean r2 of 0.85 and 0.82, respectively), but the 3B43 product was slightly better in terms of bias estimation (1.02 and 1.00). Despite reasonable doubts that have been expressed in studies of other tropical regions, within the Congo basin the TRMM science product (3B43) performed in a manner that is comparable to the performance of the recalibrated product that is described in this study.
Simulation of Flash-Flood-Producing Storm Events in Saudi Arabia Using the Weather Research and Forecasting Model*
Authors: Deng Liping , McCabe Matthew F. , Stenchikov Georgiy , Evans Jason P. , Kucera Paul A.
Published: December 2014

The challenges of monitoring and forecasting flash-flood-producing storm events in data-sparse and arid regions are explored using the Weather Research and Forecasting (WRF) Model (version 3.5) in conjunction with a range of available satellite, in situ, and reanalysis data. Here, we focus on characterizing the initial synoptic features and examining the impact of model parameterization and resolution on the reproduction of a number of flood-producing rainfall events that occurred over the western Saudi Arabian city of Jeddah. Analysis from the European Centre for Medium-Range Weather Forecasts (ECMWF) interim reanalysis (ERA-Interim) data suggests that mesoscale convective systems associated with strong moisture convergence ahead of a trough were the major initial features for the occurrence of these intense rain events. The WRF Model was able to simulate the heavy rainfall, with driving convective processes well characterized by a high-resolution cloud-resolving model. The use of higher (1 km vs 5 km) resolution along the Jeddah coastline favors the simulation of local convective systems and adds value to the simulation of heavy rainfall, especially for deep-convection-related extreme values. At the 5-km resolution, corresponding to an intermediate study domain, simulation without a cumulus scheme led to the formation of deeper convective systems and enhanced rainfall around Jeddah, illustrating the need for careful model scheme selection in this transition resolution. In analysis of multiple nested WRF simulations (25, 5, and 1 km), localized volume and intensity of heavy rainfall together with the duration of rainstorms within the Jeddah catchment area were captured reasonably well, although there was evidence of some displacements of rainstorm events.
National patterns of income and wealth inequality
Authors: Skopek Nora , Buchholz Sandra , Blossfeld Hans-Peter
Published: December 2014

The aim of this article is to show that wealth must be treated as a distinct dimension of social stratification alongside income. In a first step, we explain why social stratification researchers have largely overlooked wealth in the past and present a detailed definition of wealth by differentiating it from income. In the empirical part of the article, we analyze the distribution of wealth across 18 countries, and we describe and compare national patterns of wealth inequality to those of income inequality making use of different data sources. Our results show – first – that there is strong variation in the distribution of wealth between these 18 countries, and – second – that levels of wealth inequality significantly differ from levels of income inequality in about half of the countries analyzed. Surprisingly high levels of wealth inequality we find in Sweden and Denmark, two countries widely considered being highly egalitarian societies. Conversely, the Southern European countries – where income inequality is relatively high – exhibit comparatively low levels of wealth inequality.
Muslim Organisation and the Mobilisations for Sharia Law in northern Nigeria: The JNI and The NSCIA
Authors: Anyia Albert
Published: December 2014

This paper examines the role of Muslim religious organisations in northern Nigeria as religious interest groups in relation to government decision-making, including their role as ‘superior Muslim influence’ in the introduction and dissemination of Sharia law in 12 northern states in Nigeria. Two of the most prominent Muslim organisations in Nigeria, the J’amatu Nasril Islam (JNI) and Nigerian Supreme Council for Islamic Affairs (NSCIA), are examined in this regard to compare and highlight their lobbying strategies in their attempt to justify claims to representing over 80 million Muslims in Nigeria. This paper suggest that Islam and the support from Muslim organisations were significant influences on government policy-makers involved in the process of adopting Sharia law in the northern states. Overall, this paper concludes that Muslim organisations have superior influence, have significantly marginalised non-Muslims and have focused on Sharia law policy, thus enabling an analysis of the relationship between religion and politics in Nigeria.
Resistance and Assent
Authors: Thornhill Theodore E.
Published: December 2014

African American history is often taught poorly in high school U.S. history courses. However, we know little about how Black students perceive and experience this situation. I use a refined racial socialization framework and interview data with 32 Black college students in the Northeast to investigate how familial racial socialization shapes their perceptions of and experience learning about African American history in high school. Findings indicate that Black students socialized into critical and colorblind interpretations of race and racism, respectively, interpret, engage with, and respond to African American history in their high school U.S. history courses in different ways.
The Impact of Visa Liberalization on Tourist Behaviors—The Case of China Outbound Market Visiting Hong Kong
Authors: Liu Anyu , McKercher Bob
Published: December 2014

The potential offered by the China outbound tourism market will create pressure on destinations to relax their visa requirements in order to capitalize on the opportunities it presents. Prior research into the impacts of visa liberalization indicates that the volume of arrivals increases substantially. However, little research has been conducted examining changes in profile of visitors and their resultant behaviors. This study examines changes in the Chinese pleasure visitor market to Hong Kong from 1998 to 2012. The study is grounded in market access theory. In addition to the significant increase of arrivals during that time, behavior patterns have changed almost completely, as independent tourists have been freed from the constraints imposed by tour group participation. The study has valuable implications for other destinations that are likely to relax visa requirements for markets like China.
Inferring Future Vacation Experience Preference from Past Vacation Choice
Authors: Crouch Geoffrey I. , Huybers Twan , Oppewal Harmen
Published: December 2014

Tourists make two fundamental decisions when they travel: where to go (destination) and what to do (experience/activity). Whereas the modeling of destination choice behavior has a substantial research history, there has been little research that has sought to model and explain the choice behavior of tourists when deciding what type of vacation experience they wish to undertake. To address this gap, this study investigates how experience types are related with regard to actual past tourism consumption and preferred future experience choice. In order to investigate these relationships, the authors employed latent class modeling on survey data from a sample of respondents who had reported their recent and intended future vacation travel choices and preferences. Despite the acknowledged importance of variety seeking in a tourism choice context, the study found strong evidence for the stability of preferred experiences. In addition, it found insightful patterns of association between experience types.
With Heart and (No) Mind? How Recipients Negatively Infer Missing Information About Politicians and How This Affects the Assessment of the Speaker
Authors: Koch Thomas , Obermaier Magdalena
Published: December 2014

Two fundamental dimensions underlie person perception: warmth and competence. We conducted three experiments to investigate how a positive or negative emphasis of only one of these dimensions (i.e., of only warmth or only competence) affects the perception of the other (complementary) dimension, and how voting intentions are influenced by these emphases. The results show that when a politician is described positively in only one of the two dimensions, people assess the complementary dimension more negatively. In addition, the negative emphasis of only one of the two dimensions also leads to a more negative assessment of the complementary dimension. Furthermore, we explore how these one-dimensional person descriptions affect the assessment of the speakers uttering them. Politicians who describe their opponents in negative terms are also evaluated negatively. On the contrary, politicians who judge others in positive terms are not necessarily evaluated positively.
Media Trust in a Community Context
Authors: Yamamoto Masahiro , Lee Tien-Tsung , Ran Weina
Published: December 2014

Prior research has examined various correlates of media trust including media consumers’ political stands and media use, objectivity in news reports, and perceived biases stemming from journalists’ political leanings. The goal of this study is to examine community contextual sources of media trust. Data from the Japanese General Social Surveys indicate that prefecture-level structural pluralism and political heterogeneity are negatively associated with measures of media trust, independent of personal characteristics of respondents. Implications are discussed in terms of the production of media messages.