bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhein Reduces Fat Weight indb/dbMouse and Prevents Diet-Induced Obesity in C57Bl/6 Mouse through the Inhibition of PPARγSignaling
Authors: Zhang Yu , Fan Shengjie , Hu Na , Gu Ming , Chu Chunxiao , Li Yiming , Lu Xiong , Huang Cheng
Published: September 2012

Rheum palmatumhas been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components ofRheum palmatumthat play the antiobesity role are still uncertain. Here, we tested the weight-reducing effect of two majorRheum palmatumcompounds ondb/dbmouse. We found that rhein (100 mg kg−1 day−1), but not emodin, reduced the fat weight indb/dbmouse. Using diet-induced obese (DIO) C57BL/6 mice, we identified that rhein blocked high-fat diet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and lowered serum cholesterol, LDL cholesterol, and fasting blood glucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptorγ(PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγantagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy.
Molecular Targets Related to Inflammation and Insulin Resistance and Potential Interventions
Authors: Hirabara Sandro M. , Gorjão Renata , Vinolo Marco A. , Rodrigues Alice C. , Nachbar Renato T. , Curi Rui
Published: September 2012

Inflammation and insulin resistance are common in several chronic diseases, such as obesity, type 2diabetes mellitus, metabolic syndrome, cancer, and cardiovascular diseases. Various studies show a relationship between these two factors, although the mechanisms involved are not completely understood yet. Here, we discuss the molecular basis of insulin resistance and inflammation and the molecular aspects on inflammatory pathways interfering in insulin action. Moreover, we explore interventions based on molecular targets for preventing or treating correlated disorders, advances for a better characterization, and understanding of the mechanisms and mediators involved in the different inflammatory and insulin resistance conditions. Finally, we address biotechnological studies for the development of new potential therapies and interventions.
Iyengar Yoga for Distressed Women: A 3-Armed Randomized Controlled Trial
Authors: Michalsen Andreas , Jeitler Michael , Brunnhuber Stefan , Lüdtke Rainer , Büssing Arndt , Musial Frauke , Dobos Gustav , Kessler Christian
Published: September 2012

Distress is an increasing public health problem. We aimed to investigate the effects of an Iyengar yoga program on perceived stress and psychological outcomes in distressed women and evaluated a potential dose-effect relationship. Seventy-two female distressed subjects were included into a 3-armed randomized controlled trial and allocated to yoga group 1 (n=24) with twelve 90 min sessions over 3 months, yoga group 2 (n=24) with 24 sessions over 3 months, or a waiting list control group (n=24). The primary outcome was stress perception, measured by Cohen Stress Scale; secondary outcomes included state trait anxiety, depression, psychological and physical quality of life (QOL), profile of Mood States, well being, and bodily complaints. After three months, women in the yoga groups showed significant improvements in perceived stress (P=0.003), state trait anxiety (P=0.021andP=0.003), depression (P=0.008), psychological QOL (P=0.012), mood states being (P=0.007), and bodily complaints well(P=0.012) when compared to controls. Both yoga programs were similarly effective for these outcomes; however, compliance was better in the group with fewer sessions (yoga group 1). Dose effects were seen only in the analysis of group-independent effects for back pain, anxiety, and depression. These findings suggest that Iyengar yoga effectively reduces distress and improves related psychological and physical outcomes. Furthermore, attending twice-weekly yoga classes was not superior to once-weekly classes, as a result of limited compliance in the twice-weekly group.
A Nonlinear Programming and Artificial Neural Network Approach for Optimizing the Performance of a Job Dispatching Rule in a Wafer Fabrication Factory
Authors: Chen Toly
Published: September 2012

A nonlinear programming and artificial neural network approach is presented in this study to optimize the performance of a job dispatching rule in a wafer fabrication factory. The proposed methodology fuses two existing rules and constructs a nonlinear programming model to choose the best values of parameters in the two rules by dynamically maximizing the standard deviation of the slack, which has been shown to benefit scheduling performance by several studies. In addition, a more effective approach is also applied to estimate the remaining cycle time of a job, which is empirically shown to be conducive to the scheduling performance. The efficacy of the proposed methodology was validated with a simulated case; evidence was found to support its effectiveness. We also suggested several directions in which it can be exploited in the future.
Statistical Convergence of Double Sequences in Locally Solid Riesz Spaces
Authors: Mohiuddine S. A. , Alotaibi Abdullah , Mursaleen M.
Published: September 2012

Recently, the notion of statistical convergence is studied in a locally solid Riesz space by Albayrak and Pehlivan (2012). In this paper, we define and study statistical τ‐convergence, statistical τ‐Cauchy and S∗(τ)‐convergence of double sequences in a locally solid Riesz space.
Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside
Authors: Moysidis Stavros N. , Thanos Aristomenis , Vavvas Demetrios G.
Published: September 2012

Proliferative vitreoretinopathy (PVR) is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD). Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGRα), which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH), daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside.
Astragaloside IV Inhibits Oxidative Stress-Induced Mitochondrial Permeability Transition Pore Opening by Inactivating GSK-3βvia Nitric Oxide in H9c2 Cardiac Cells
Authors: He Yonggui , Xi Jinkun , Zheng Huan , Zhang Yidong , Jin Yuanzhe , Xu Zhelong
Published: September 2012

Objective. This study aimed to investigate whether astragaloside IV modulates the mitochondrial permeability transition pore (mPTP) opening through glycogen synthase kinase 3β(GSK-3β) in H9c2 cells.Methods. H9c2 cells were exposed to astragaloside IV for 20 min. GSK-3β(Ser9), Akt (Ser473), and VASP (Ser239) activities were determined with western blot. The mPTP opening was evaluated by measuring mitochondrial membrane potential (ΔΨm). Nitric oxide (NO) generation was measured by 4-amino-5-methylamino-2′,7′-difluorofluorescein (DAF-FM) diacetate. Fluorescence images were obtained with confocal microscopy.Results. Astragaloside IV significantly enhanced GSK-3βphosphorylation and prevented H2O2-induced loss ofΔΨm. These effects of astragaloside IV were reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the NO sensitive guanylyl cyclase selective inhibitor ODQ, and the PKG inhibitor KT5823. Astragaloside IV activated Akt and PKG. Astragaloside IV was also shown to increase NO production, an effect that was reversed by L-NAME and LY294002. Astragaloside IV applied at reperfusion reduced cell death caused by simulated ischemia/reperfusion, indicating that astragaloside IV can prevent reperfusion injury. Conclusions. These data suggest that astragaloside IV prevents the mPTP opening and reperfusion injury by inactivating GSK-3βthrough the NO/cGMP/PKG signaling pathway. NOS is responsible for NO generation and is activated by the PI3K/Akt pathway.
Interval Oscillation Criteria of Second‐Order Nonlinear Dynamic Equations on Time Scales
Authors: Qiu Yang-Cong , Wang Qi-Ru
Published: September 2012

Using functions in some function classes and a generalized Riccati technique, we establish
interval oscillation criteria for second‐order nonlinear dynamic equations on time scales of the form . The obtained interval oscillation criteria can be applied to equations with a forcing term. An example
is included to show the significance of the results.
The Effects of Walking or Walking-with-Poles Training on Tissue Oxygenation in Patients with Peripheral Arterial Disease
Authors: Collins Eileen G. , McBurney Conor , Butler Jolene , Jelinek Christine , O'Connell Susan , Fritschi Cynthia , Reda Domenic
Published: September 2012

This randomized trial proposed to determine if there were differences in calf muscle StO2parameters in patients before and after 12 weeks of a traditional walking or walking-with-poles exercise program. Data were collected on 85 patients who were randomized to a traditional walking program () or walking-with-poles program () of exercise training. Patients walked for 3 times weekly for 12 weeks. Seventy-one patients completed both the baseline and the 12-week follow-up progressive treadmill tests ( traditional walking and walking-with-poles). Using the near-infrared spectroscopy measures, StO2was measured prior to, during, and after exercise. At baseline, calf muscle oxygenation decreased from % prior to the treadmill test to % at peak exercise. The time elapsed prior to reaching nadir StO2values increased more in the traditional walking group when compared to the walking-with-poles group. Likewise, absolute walking time increased more in the traditional walking group than in the walking-with-poles group. Tissue oxygenation decline during treadmill testing was less for patients assigned to a 12-week traditional walking program when compared to those assigned to a 12-week walking-with-poles program. In conclusion, the 12-week traditional walking program was superior to walking-with-poles in improving tissue deoxygenation in patients with PAD.
Challenges in the Enumeration and Phenotyping of CTC
Authors: Coumans Frank A.W. , Ligthart Sjoerd T. , Uhr Jonathan W. , Terstappen Leon W.M.M.
Published: September 2012

Purpose: Presence of circulating tumor cells (CTC) in metastatic carcinoma is associated with poor survival. Phenotyping and genotyping of CTC may permit “real-time” treatment decisions, provided CTCs are available for examination. Here, we investigate what is needed to detect CTC in all patients.

Experimental Design: CTCs enumerated in 7.5 mL of blood together with survival from 836 patients with metastatic breast, colorectal, and prostate cancer were used to predict the CTC concentration in the 42% of these patients in whom no CTCs were found and to establish the relation of concentration of CTCs with survival. Influence of different CTC definitions were investigated by automated cell recognition and a flow cytometric assay without an enrichment or permeabilization step.

Results: A log-logistic regression of the log of CTC yielded a good fit to the CTC frequency distribution. Extrapolation of the blood volume to 5 L predicted that 99% of patients had at least one CTC before therapy initiation. Survival of patients with EpCAM+, cytokeratin+, CD45− nucleated CTCs is reduced by 6.6 months for each 10-fold CTC increase. Using flow cytometry, the potential three-fold recovery improvement is not sufficient to detect CTC in all patients in 7.5 mL of blood.

Conclusions: EpCAM+, cytokeratin+, CD45− nucleated CTCs are present in all patients with metastatic breast, prostate, and colorectal cancer and their frequency is proportional to survival. To serve as a liquid biopsy for the majority of patients, a substantial improvement of CTC yield is needed, which can only be achieved by a dramatic increase in sample volume. Clin Cancer Res; 18(20); 5711–8. ©2012 AACR.
Cancer Cell Metabolism: One Hallmark, Many Faces
Authors: Cantor Jason R. , Sabatini David M.
Published: September 2012

Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

Significance: Altered tumor metabolism is now a generally regarded hallmark of cancer. Nevertheless, the recognition of metabolic heterogeneity in cancer is becoming clearer as a result of advancements in several tools used to interrogate metabolic rewiring and dependencies. Deciphering this context-dependent heterogeneity will supplement our current understanding of tumor metabolism and may yield promising therapeutic and diagnostic utilities. Cancer Discov; 2(10); 881–98. ©2012 AACR.
Hydrogen Peroxide in Exhaled Breath Condensate in Asthmatic Children during Acute Exacerbation and after Treatment
Authors: Caffarelli Carlo , Calcinai Elena , Rinaldi Laura , Povesi Dascola Carlotta , Terracciano Luigi , Corradi Massimo
Published: September 2012

Background: In asthmatics, the concentration of hydrogen peroxide (H2O2) in exhaled breath condensate (EBC) has been found to be increased and to be related to airway inflammation. Objective: The aim of this study was to determine whether in children with acute exacerbation, exhaled H2O2 levels could be influenced by treatment and linked to airway obstruction. Methods: Twenty-two asthmatic children (mean age 9.4 years, range 6–14) with asthma exacerbation and 12 healthy children (mean age 11.7 years, range 7–15) were enrolled. Concentrations of exhaled H2O2 before and after standard treatment for asthma attack were compared with those of controls and with clinical observation. Asthmatic children and controls underwent spirometry and skin prick tests to common aeroallergens. Results: Exhaled H2O2 concentrations were significantly higher in children with asthma both before (median 0.273 µm; p < 0.001) and after pharmacologic treatment (median 0.303 µm; p = 0.001) compared to control values (median 0.045 µm). After treatment, exhaled H2O2 concentrations remained significantly higher in children with and without auscultatory wheezing than in controls (p = 0.034 and p < 0.001, respectively). EBC H2O2 levels in asthmatics before treatment did not differ from those after treatment. No correlation was found between H2O2 and forced expiratory volume in 1 s values. All asthmatics but one were atopics. Conclusions: In children with acute asthma exacerbation, exhaled H2O2 concentrations in EBC are significantly elevated. In the short-term follow-up, H2O2 levels remain at high levels and are not correlated with lung function or improvement in symptoms.
Small Particle-Size Talc Is Associated with Poor Outcome and Increased Inflammation in Thoracoscopic Pleurodesis
Authors: Arellano-Orden Elena , Romero-Falcon Auxiliadora , Juan José Martin , Ocaña Jurado Manuel , Rodriguez-Panadero Francisco , Montes-Worboys Ana
Published: September 2012

Rationale: Talc is very effective for pleurodesis, but there is concern about complications, especially acute respiratory distress syndrome. Objectives: It was the aim of this study to investigate if talc with a high concentration of small particles induces greater production of cytokines, and if pleural tumor burden has any influence on the local production and spillover of cytokines to the systemic circulation and eventual complications. Methods: We investigated 227 consecutive patients with malignant effusion submitted to talc pleurodesis. One hundred and three patients received ‘small-particle talc' (ST; containing about 50% particles <10 µm) and 124 received ‘large-particle talc' (with <20% particles <10 µm). Serial samples of both pleural fluid and blood were taken before and 3, 24, 48 and 72 h after thoracoscopy. Also, mesothelial cells were stimulated with both types of talc in vitro. Measurements and Results: Interleukin-8, tumor necrosis factor-α, vascular endothelial growth factor, basic fibroblast growth factor and thrombin-antithrombin complex were measured in all samples. Early death (<7 days after talc) occurred in 8 of 103 patients in the ST and in 1 of 124 in the ‘large-particle talc' group (p = 0.007). Patients who received ST had significantly higher proinflammatory cytokines in pleural fluid and serum after talc application, and also in supernatants of the in vitro study. Pleural tumor burden correlated positively with proinflammatory cytokines in serum, suggesting that advanced tumor states induce stronger systemic reactions after talc application. Conclusions: ST provokes a strong inflammatory reaction in both pleural space and serum, which is associated with a higher rate of early deaths observed in patients receiving it.
Incidence and Clinical Impact of Stent Fracture After Everolimus-Eluting Stent Implantation
Authors: Kuramitsu Shoichi , Iwabuchi Masashi , Haraguchi Takuya , Domei Takenori , Nagae Ayumu , Hyodo Makoto , Yamaji Kyohei , Soga Yoshimitsu , Arita Takeshi , Shirai Shinichi , Kondo Katsuhiro , Ando Kenji , Sakai Koyu , Goya Masahiko , Takabatake Yoshitaka , Sonoda Shinjo , Yokoi Hiroyoshi , Toyota Fumitoshi , Nosaka Hideyuki , Nobuyoshi Masakiyo
Published: September 2012

Background—

Stent fracture (SF) after drug-eluting stent implantation has recently become an important concern because of its potential association with in-stent restenosis and stent thrombosis. However, the incidence and clinical impact of SF after everolimus-eluting stent implantation remain unclear.

Methods and Results—

A total of 1035 patients with 1339 lesions undergoing everolimus-eluting stent implantation and follow-up angiography 6 to 9 months after index procedure were analyzed. SF was defined as complete or partial separation of the stent, as assessed by plain fluoroscopy or intravascular ultrasound during follow-up. We assessed the rates of SF and major adverse cardiac events, defined as cardiac death, myocardial infarction, stent thrombosis, and clinically driven target lesion revascularization within 9 months. SF was observed in 39 of 1339 lesions (2.9%) and in 39 of 1035 patients (3.8%). Ostial stent location and lesions with hinge motion, tortuosity, or calcification were independent predictors of SF. The rate of myocardial infarction and target lesion revascularization were significantly higher in the SF group than in the non-SF group (5.1% versus 0.4%;
P
=0.018 and 25.6% versus 2.0%;
P
<0.001, respectively). Stent thrombosis was more frequently observed in the SF group than in the non-SF group (5.1% versus 0.4%;
P
=0.018). Major adverse cardiac events within 9 months were significantly higher in the SF group than in the non-SF group (25.6% versus 2.3%;
P
<0.001).

Conclusions—

SF after everolimus-eluting stent implantation occurs in 2.9% of lesions and is associated with higher rate of major adverse cardiac events, driven by higher target lesion revascularization and stent thrombosis.
Tbx1
Genetically Interacts With the Transforming Growth Factor-β/Bone Morphogenetic Protein Inhibitor
Smad7
During Great Vessel Remodeling
Authors: Papangeli Irinna , Scambler Peter J.
Published: September 2012

Rationale:

Growth and remodeling of the pharyngeal arch arteries are vital for the development of a mature great vessel system. Dysmorphogenesis of the fourth arch arteries can result in interruption of the aortic arch type B, typically found in DiGeorge syndrome.
Tbx1
haploinsufficient embryos, which model DiGeorge syndrome, display fourth arch artery defects during formation of the vessels. Recovery from such defects is a documented yet unexplained phenotype in
Tbx1
haploinsufficiency.

Objective:

To understand the nature of fourth arch artery growth recovery in
Tbx1
haploinsufficiency and its underlying genetic control.

Methods and Results:

We categorized vessel phenotypes of
Tbx1
heterozygotes as hypoplastic or aplastic at the conclusion of pharyngeal artery formation and compared these against the frequency of vessel defects scored at the end of great vessel development. The frequency of hypoplastic vessels decreased during embryogenesis, whereas no reduction of vessel aplasia was seen, implying recovery is attributable to remodeling of hypoplastic vessels. We showed that
Smad7
, an inhibitory Smad within the transforming growth factor-β pathway, is regulated by Tbx1, is required for arch artery remodeling, and genetically interacts with
Tbx1
in this process.
Tbx1
and
Tbx1
;
Smad7
haploinsufficiency affected several remodeling processes; however, concurrent haploinsufficiency particularly impacted on the earliest stage of vascular smooth muscle cell vessel coverage and subsequent fibronectin deposition. Conditional reconstitution of
Smad7
with a
Tbx1Cre
driver indicated that the interaction between the 2 genes is cell autonomous.

Conclusions:

Tbx1
acts upstream of
Smad7
controlling vascular smooth muscle and extracellular matrix investment of the fourth arch artery.
Rho-Associated Coiled-Coil-Containing Kinase 2 Deficiency in Bone Marrow–Derived Cells Leads to Increased Cholesterol Efflux and Decreased Atherosclerosis
Authors: Zhou Qian , Mei Yu , Shoji Takuhito , Han Xinbing , Kaminski Karol , Oh Goo Taeg , Ongusaha Pat P. , Zhang Kunzhong , Schmitt Hannah , Moser Martin , Bode Christoph , Liao James K.
Published: September 2012

Background—

Macrophages play a central role in the development of atherosclerosis. However, the signaling pathways that regulate their function are not well understood. The Rho-associated coiled-coil-containing kinases (ROCK1 and ROCK2) are serine-threonine protein kinases that are involved in the regulation of the actin cytoskeleton. Recent studies suggest that ROCK1 in macrophages and bone marrow–derived cells mediates atherogenesis. However, a similar role for ROCK2 in the pathogenesis of atherosclerosis has not been determined.

Methods and Results—

The bone marrows from wild-type, ROCK2
+/−
, and ROCK2
−/−
mice were transplanted into irradiated recipient low-density lipoprotein receptor
−/−
mice, and atherosclerosis was induced with a 16-week high-cholesterol diet. Compared with wild-type bone marrow–transplanted mice, ROCK2
+/−
bone marrow–transplanted and ROCK2
−/−
bone marrow–transplanted mice showed substantially less lipid accumulation in the aorta (8.46±1.42% and 9.80±2.34% versus 15.64±1.89%;
P
<0.01 for both) and decreased atherosclerotic lesions in the subaortic sinus (158.1±44.4 and 330.1±109.5×10
3
μm
2
versus 520.2±125.7×10
3
μm
2
;
P
<0.01 for both). These findings correlated with decreased foam cell formation (2.27±0.57 versus 4.10±0.3;
P
<0.01) and increased cholesterol efflux (17.65±0.6 versus 9.75±0.8;
P
<0.05) in ROCK2-deficient mice that are mediated, in part, through the peroxisome proliferator-activated receptor-γ/liver X receptor/ATP-binding cassette transporter A1 pathway in macrophages.

Conclusions—

ROCK2 contributes to atherosclerosis, in part, by inhibiting peroxisome proliferator-activated receptor-γ–mediated reverse cholesterol transport in macrophages, which contributes to foam cell formation. These findings suggest that inhibition of ROCK2 in macrophages may have therapeutic benefits in preventing the development of atherosclerosis.
Will Delays in Treatment Jeopardize the Population Benefit From Extending the Time Window for Stroke Thrombolysis?
Authors: Pitt Martin , Monks Thomas , Agarwal Paritosh , Worthington David , Ford Gary A. , Lees Kennedy R. , Stein Ken , James Martin A.
Published: September 2012

Background and Purpose—

Pooled analyses show benefits of intravenous alteplase (recombinant tissue-type plasminogen activator) treatment for acute ischemic stroke up to 4.5 hours after onset despite marketing approval for up to 3 hours. However, the benefit from thrombolysis is critically time-dependent and if extending the time window reduces treatment urgency, this could reduce the population benefit from any extension.

Methods—

Based on 3830 UK patients registered between 2005 to 2010 in the Safe Implementation of Treatments in Stroke–International Stroke Thrombolysis Registry (SITS-ISTR), a Monte Carlo simulation was used to model recombinant tissue-type plasminogen activator treatment up to 4·5 hours from onset and assess the impact (numbers surviving with little or no disability) from changes in hospital treatment times associated with this extended time window.

Results—

We observed a significant relation between time remaining to treat and time taken to treat in the UK SITS-ISTR data set after adjustment for censoring. Simulation showed that as this “deadline effect” increases, an extended treatment time window entails that an increasing number of patients are treated at a progressively lower absolute benefit to a point where the population benefit from extending the time window is entirely negated.

Conclusions—

Despite the benefit for individual patients treated up to 4.5 hours after onset, the population benefit may be reduced or lost altogether if extending the time window results in more patients being treated but at a lower absolute benefit. A universally applied reduction in hospital arrival to treatment times of 8 minutes would confer a population benefit as large as the time window extension.
Identification of a Genetic Variant Common to Moyamoya Disease and Intracranial Major Artery Stenosis/Occlusion
Authors: Miyawaki Satoru , Imai Hideaki , Takayanagi Shunsaku , Mukasa Akitake , Nakatomi Hirofumi , Saito Nobuhito
Published: September 2012

Background and Purpose—

The c.14576G>A variant in ring finger protein 213 (RNF213) was recently identified as a susceptibility gene variant for moyamoya disease (MMD). The occurrence of c.14576G>A variant was evaluated in patients with intracranial major artery stenosis/occlusion (ICASO) without signs of MMD (non-MMD ICASO), as well as in patients with MMD and other cerebrovascular diseases as controls.

Methods—

This single-hospital–based case-control study was completed in 7 months (from October 2011–April 2012) at Department of Neurosurgery, The University of Tokyo Hospital. The occurrence of c.14576G>A variant was analyzed in 41 patients with non-MMD ICASO, in 48 with MMD, in 21 with cervical disease, in 61 with cerebral aneurysm, and in 25 normal subjects.

Results—

Nine of 41 patients (21.9%) with non-MMD ICASO and 41 of 48 (85.4%) with MMD had the c.14576G>A variant. One of 61 patients (1.6%) with cerebral aneurysm and no patients with cervical disease or normal subjects had the variant. Comparison of each phenotype group with the normal subjects showed that presence of c.14576G>A variant had significant associations with MMD (odds ratio [OR], 292.8; 95% confidence interval [CI], 15.4–5153.0; P<0.0001) and with non-MMD ICASO (OR, 14.9; 95% CI, 0.82–268.4; P=0.01), but no association with either cerebral aneurysm (OR, 1.2; 95% CI, 0.04–32.0; P=1.00) or cervical disease (OR, 1.1; 95% CI, 0.02–62.3; P=1.00).

Conclusions—

The present study indicates that a particular subset of Japanese patients with non-MMD ICASO has a genetic variant associated with MMD. Therefore, we propose the existence of a new entity of ICASO caused by the c.14576G>A variant in RNF213.
Poststroke Hypertension in Africa
Authors: Kaddumukasa Martin , Ddumba Edward , Duncan Pamela , Goldstein Larry B.
Published: September 2012

Background and Purpose—

Little is known about the frequency of hypertension and related knowledge in Africans who have had a stroke. The objective of this study was to determine the frequency of hypertension, its control, and associated knowledge among patients with and without a history of stroke at Uganda’s main referral hospital.

Methods—

Subjects with a history of stroke (n=157) were compared with stroke-free control subjects (n=149). Demographics and clinical characteristics were recorded and hypertension-related knowledge assessed by questionnaire. Multiple logistic regression including cases and control subjects was used to determine factors independently associated with blood pressure control and hypertension-related knowledge.

Results—

A total of 69.4% of cases versus 54.7% of control subjects were hypertensive at the time of the research visit (
P
=0.001). Univariable analyses showed the odds of having good blood pressure control (OR, 0.53; 95% CI, 0.33–0.84;
P
=0.006) and good hypertension knowledge (OR, 0.35; 95% CI, 0.22–0.56;
P
<0.0001) were lower in cases. Age <40 years (
P
=0.002), good hypertension-related knowledge (
P
=0.002), and poorer medication adherence (
P
<0.0001) were independently associated with poorer blood pressure control. Those with a history of hypertension had better hypertension-related knowledge (
P
=0.001), but knowledge was poorer among cases (
P
<0.0001).

Conclusion—

Hypertension is common in Ugandans with and without a history of stroke. Barriers to effective blood pressure control in Uganda other than patient knowledge need to be identified.
Assessing Dimensionality of Noncompensatory Multidimensional Item Response Theory With Complex Structures
Authors: Svetina Dubravka
Published: September 2012

The purpose of this study was to investigate the effect of complex structure on dimensionality assessment in noncompensatory multidimensional item response models using dimensionality assessment procedures based on DETECT (dimensionality evaluation to enumerate contributing traits) and NOHARM (normal ogive harmonic analysis robust method). Five methods were evaluated: two DETECT-based methods—exploratory and cross-validated—and three NOHARM-based methods: root mean square residual (RMSR), [Formula: see text], and approximate likelihood ratio (ALR). The results suggested that the studied methods had varying degree of success in correctly counting the number of dimensions and in meaningfully labeling sets of items as dimension-like. In two-dimensional, shorter tests, [Formula: see text] and ALR largely outperformed RMSR- and DETECT-based methods in conditions with small and medium sample sizes, across all levels of complexity and correlations. Lengthening of the test in two-dimensional conditions led to most notably improved accuracy in determining the correct number of dimensions for NOHARM-based RMSR, whereas for the remaining methods, increase in the number of items had differential effect. DETECT-based methods, on the other hand, had more success in labeling sets of items as dimension-like in conditions with two dimensions, irrespective of the test length, suggesting the items that ought to be together were more often grouped together. Performance of the methods was further evaluated in conditions with larger dimensionality (i.e., 3) and conditions with the increased number of items (i.e., longer tests).
Factors Associated with Alkali Production from Arginine in Dental Biofilms
Authors: Huang X. , Exterkate R.A.M. , ten Cate J.M.
Published: September 2012

Alkali production by oral bacteria in the oral cavity has been linked to protection against dental caries. The current study assessed various parameters associated with ammonium produced during arginine catabolism in dental biofilms. Polymicrobial biofilms were formed with saliva as the inoculum. The NH3 level and the pH of the spent medium were used to monitor and quantitate the bacterial reactions. The presence of sucrose, a low buffer capacity, and a low pH (≤ pH 4.5) were found to hamper alkali production from arginine. The rate of alkali production exhibited an optimum around pH 5.5. Biofilms were found to produce NH3 also from polypeptides and proteins in the medium. The biofilm age affected these processes. The experimental model proved valuable for the assessment of the collective bacterial reactions determining the overall pH outcome. This experimental approach could bridge the gap in our knowledge between pH-rise phenomena and caries susceptibility from clinical observations and studies performed on alkali-producing bacteria in well- controlled, though simplified, in vitro models. Analysis of our data supports the hypothesis that the initiation and progression of dental caries may be influenced by the relative rates of acid and base formation, which critically depend on the aforementioned parameters.
SHP is Involved in BMP2-induced Odontoblast Differentiation
Authors: Oh S.H. , Hwang Y.C. , Yang H. , Kang J.H. , Hur S.W. , Jung N.R. , Jang W.G. , Lee K.N. , Oh W.M. , Park J.C. , Kim S.H. , Koh J.T.
Published: September 2012

Small Heterodimer Partner (SHP) interacts with diverse transcription factors such as Runx2 and regulates many cellular events including differentiation, proliferation, and energy metabolism. SHP is reported to be a positive regulator of BMP2-induced bone formation. This study aimed to clarify the role of SHP in odontoblast differentiation and matrix mineralization. Rat tooth germs were isolated, and gene expression was determined by RT-PCR and real-time PCR. Localization of SHP protein expression was identified by immunofluorescent analysis. Primary human dental pulp cells (HDPCs) were cultured with BMP2 and/or Ad-siSHP. Matrix mineralization was evaluated by Alizarin red staining. Transient transfection experiment was performed with the SHP or Dlx5 expressional plasmids and the DSPP gene. In tooth germs from post-natal days 3 to 9, BMP-2 and SHP expression increased with DSPP and DMP1 mRNA expression. In an immunostaining study, SHP was expressed in odontoblasts and surrounding osteoblasts. When HDPCs were cultured with BMP2 in mineralization-inducing medium, SHP expression also increased with an increase in DSPP expression. Down-regulation of SHP by Ad-siSHP inhibited matrix mineralization. In transient transfection experiments, overexpression of SHP was shown to enhance DSPP promoter activity through interactions between SHP and Dlx5. These results suggest that SHP may mediate BMP2 signaling to promote mineralization of the dentin matrix.
Branding the City: The Democratic Legitimacy of a New Mode of Governance
Authors: Eshuis Jasper , Edwards Arthur
Published: September 2012

Place branding has been used to influence ideas concerning communities and districts, especially in regeneration programmes. This article approaches branding as a new governance strategy for managing perceptions. Considering the popular criticism that branding is a form of spin that prevents the public from gaining a proper understanding of their government’s policies, this article focuses on the democratic legitimacy of branding in urban governance. The branding of two urban communities in the Netherlands is examined empirically in terms of input legitimacy, throughput legitimacy and output legitimacy. The research shows how the democratic legitimacy of branding varies in the two cases. In one case, branding largely excluded citizens, whereas in the other case there was limited citizen participation. The article indicates that, although branding can potentially be a participatory process in which the feelings and emotions of citizens are included, this potential is not always fully realised in practice.
Uruguay 2008
Authors: Ruffinelli Jorge
Published: September 2012

The year 2008 was prolific in terms of documentary film production in Uruguay. This type of Uruguayan cinema, which dates to the 1960s, was interrupted by the military dictatorship (1973–1984), and on the return of democracy it was very slow to recover. In 2008, however, it showed great vitality as political expression and great diversity in the artistic forms it employed in observing and interpreting the reality of the recent past.

El año 2008 fue prolífico en lo que concierne la producción del cine documental en Uruguay. Este tipo de cine uruguayo, que data a los 1960, se interrumpió con la dictadura militar (1973–1984), y en la vuelta a la democracia se recuperó muy lentamente. Sin embargo en 2008 mostró gran vitalidad como expresión política y gran diversidad en las formas artísticas que se empleaban en observar e interpretar la realidad del pasado reciente.
Conceptualizing the Civil–Military Gap
Authors: Rahbek-Clemmensen Jon , Archer Emerald M. , Barr John , Belkin Aaron , Guerrero Mario , Hall Cameron , Swain Katie E. O.
Published: September 2012

The authors suggest that scholars mean very different things when they refer to the civil–military gap. To illustrate the point, the authors conceptualize the gap in terms of four distinct ideal types and show that scholars have referred to each variant as the civil–military gap at different times. Though the authors recognize that the four ideal types—cultural, demographic, policy preference, and institutional—are not always mutually exclusive, the authors suggest that they are divergent enough to warrant consideration as distinct variants and that their specification can enhance the civil–military relations literature by helping scholars identify and untangle the causes and effects of the gap.
Action Sport NGOs in a Neo-Liberal Context
Authors: Thorpe Holly , Rinehart Robert
Published: September 2012

Sport nongovernmental organizations (NGOs) have flourished in the contemporary moment, particularly situated within neoliberal global politics. In this article we focus on the relatively recent proliferation of action sport-based social justice advocacy groups. Drawing on extant materials from our ongoing research on two action sport-related social justice movements—Skateistan and SurfAid International (SAI)—we illustrate some of the unique strategies employed by these organizations to survive, and indeed thrive, within a neo-liberally-dominated world. In so doing, we hope to raise new questions for critical scholars interested in studying sport-related NGOs into the 21st century.
Reforming a Bachelor of Music programme: A case study
Authors: Carey Gemma , Lebler Don
Published: September 2012

In 2010, the authors conducted a formal review of the Queensland Conservatorium’s Bachelor of Music programme to determine to what extent the programme prepared graduates for professional life in the 21st century. The process was informed by comprehensive performance indicator data and substantial feedback from staff, students, and other stakeholders. Information was collected through meetings with staff and students, student evaluations, graduate surveys, and feedback from the music industry, along with benchmarking with other Australian and International tertiary music institutions. The review found that teachers at the Conservatorium were committed to striving for excellence yet strong criticism was made of the existing programme’s perceived limitations in preparing students for their likely futures. Following extensive consultation, consensus reflecting the review recommendations was reached, resulting in a new Bachelor of Music programme design. This article reports on the process undertaken and the major changes that are now being implemented.
Burnout Among Public Service Workers
Authors: Hsieh Chih-Wei
Published: September 2012

Current literature remains inconclusive regarding the adverse impact of emotional labor requirements on burnout. To address the discrepancy, this study revisited this relationship as well as investigated the potential additive and interactive effects of job resources, namely job control, social support, and rewards. In the sample of 208 public service workers, regression results revealed that display rules that require expression of positive emotions did not account for variance in emotional exhaustion whereas display rules that require suppression of negative emotions were emotionally taxing. Job resources were uniformly associated with decreased emotional exhaustion. Moreover, coworker support significantly attenuated the harmful impact of emotional demands. Based on these findings, this study suggests, rather than emphasizing negative display rules, it is more favorable for organizations to specify appropriate expressions of job-related emotions. When workers are at risk of burnout, provision of job resources can help ease the burden and reduce job stress.
Dopamine Is Involved in Food-Anticipatory Activity in Mice
Authors: Liu Yuan-Yuan , Liu Tian-Ya , Qu Wei-Min , Hong Zong-Yuan , Urade Yoshihiro , Huang Zhi-Li
Published: September 2012

When food is available during a restricted and predictable time of the day, mammals exhibit food-anticipatory activity (FAA), an increase in locomotor activity preceding the presentation of food. Although many studies have attempted to locate the food-entrainable circadian oscillator in the central nervous system, the pathways that mediate food entrainment are a matter of controversy. The present study was designed to determine the role of dopaminergic and histaminergic systems on FAA. Mice were given access to food for 2 h (ZT12-ZT14), and FAA was defined as the locomotor activity that occurred 2 h before the availability of food. Dopamine D1 receptor (R), D2R, and histamine H1R-specific antagonists were used to clarify the role of dopamine and histamine receptors in FAA induced by food restriction (FR). FAA was monitored by infrared locomotor activity sensors. Mice were sacrificed at ZT12 on the 14th day of FR, and monoamine concentrations were determined by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ECD). The results showed that pretreatment with the D1R antagonist SCH23390 at 1, 3, or 10 µg/kg significantly reduced FAA by 19% ( p < 0.05), 26% ( p < 0.05), or 19% ( p < 0.01), respectively, and the D2R antagonist raclopride at 22, 67, or 200 µg/kg significantly reduced FAA by 16% ( p < 0.05), 36% ( p < 0.01), or 41% ( p < 0.01), respectively, as compared with vehicle control. Moreover, coadministration of SCH23390 (10 µg/kg) and raclopride (200 µg/kg) synergistically inhibited FAA by 57% ( p < 0.01) as compared with vehicle control. Consistently, the levels of dopamine and its metabolites in the striatum and midbrain were significantly increased during FAA, even with the pretreatment of D1R and D2R antagonists. However, pretreatment with pyrilamine at 2.5, 5, or 10 mg/kg did not significantly reduce FAA, although it reduced the locomotor activity during the dark period in ad libitum mice. These results strongly indicate that the dopaminergic system plays an essential role in the FAA in mice.
Cellular Circadian Clocks in Mood Disorders
Authors: McCarthy Michael J. , Welsh David K.
Published: September 2012

Bipolar disorder (BD) and major depressive disorder (MDD) are heritable neuropsychiatric disorders associated with disrupted circadian rhythms. The hypothesis that circadian clock dysfunction plays a causal role in these disorders has endured for decades but has been difficult to test and remains controversial. In the meantime, the discovery of clock genes and cellular clocks has revolutionized our understanding of circadian timing. Cellular circadian clocks are located in the suprachiasmatic nucleus (SCN), the brain’s primary circadian pacemaker, but also throughout the brain and peripheral tissues. In BD and MDD patients, defects have been found in SCN-dependent rhythms of body temperature and melatonin release. However, these are imperfect and indirect indicators of SCN function. Moreover, the SCN may not be particularly relevant to mood regulation, whereas the lateral habenula, ventral tegmentum, and hippocampus, which also contain cellular clocks, have established roles in this regard. Dysfunction in these non-SCN clocks could contribute directly to the pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non-SCN clocks is a trait marker of mood disorders, encoded by pathological genetic variants. Because network features of the SCN render it uniquely resistant to perturbation, previous studies of SCN outputs in mood disorders patients may have failed to detect genetic defects affecting non-SCN clocks, which include not only mood-regulating neurons in the brain but also peripheral cells accessible in human subjects. Therefore, reporters of rhythmic clock gene expression in cells from patients or mouse models could provide a direct assay of the molecular gears of the clock, in cellular clocks that are likely to be more representative than the SCN of mood-regulating neurons in patients. This approach, informed by the new insights and tools of modern chronobiology, will allow a more definitive test of the role of cellular circadian clocks in mood disorders.
Sympatric Drosophilid Species melanogaster and ananassae Differ in Temporal Patterns of Activity
Authors: Prabhakaran Priya M. , Sheeba Vasu
Published: September 2012

The fruit fly Drosophila melanogaster has long served as a model system for circadian rhythm research. Various aspects of its genetic, molecular, and circuit-level properties are the subject of investigation, based on which several circadian behaviors and their neuronal controls have been unraveled. In an attempt to address the question of functional significance of circadian organization using a comparative approach, we studied activity/rest rhythm of wild-caught D. melanogaster (DM) and its close relative, Drosophila ananassae (DA). We compared features of the rhythm such as the ability to anticipate morning and evening transitions, presence or absence of morning-associated or evening-associated activity peaks, and phase of these peaks in both species. We found that these 2 sympatric species are different from each other in several aspects of activity/rest rhythm. Unlike DM, which showed a distinct bimodal activity pattern with both morning and evening peaks and a midday interval of relative inactivity under a 12:12-h light/dark regime, DA exhibited unimodal activity with a predominant morning peak, restricting most of its activity to the light phase with no apparent “siesta” during midday. While daytime sleep levels were not different between the 2 species, DA exhibited significantly lesser nighttime activity and higher, more consolidated sleep. This predominant morning activity of DA was also reflected in persistence and phasing of the morning peak under a range of photoperiods. Both under long and short days, the morning peak was the most dominant and persistent peak of DA, whereas the evening peak was more dominant in DM. In addition, DA had a significantly faster circadian clock and more consolidated activity compared with DM. Hence, we hypothesize that these recently diverged sympatric species of fruit flies occupy distinct temporal niches due to differences in their underlying circadian clocks and speculate that they occupy different spatial microenvironments in the wild.