bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of HIF Prolyl Hydroxylase-2 Blocks Tumor Growth in Mice through the Antiproliferative Activity of TGFβ
Authors: Ameln Anne Klotzsche-von , Muschter Antje , Mamlouk Soulafa , Kalucka Joanna , Prade Ina , Franke Kristin , Rezaei Maryam , Poitz David M. , Breier Georg , Wielockx Ben
Published: March 2011

Virtually all solid tumors are dependent on a vascular network to provide them with the right amount of nutrients and oxygen. In that sense, low oxygen tension or hypoxia leads to an adaptive response that is transcriptionally regulated by the hypoxia-inducible factors (HIF), which are tightly controlled by the HIF prolyl hydroxylases (PHD). In this study, we show that inhibition of the oxygen sensor PHD2 in tumor cells stimulates vessel formation but paradoxically results in a profound reduction of tumor growth. This effect relies on the antiproliferative nature of the TGFβ signaling pathway, in a largely HIF-independent manner. Moreover, our findings reveal that PHD2 has an essential function in controlling the dual nature of TGFβ during tumorigenesis and may offer an alternative opportunity for anticancer therapy. Cancer Res; 71(9); 3306–16. ©2011 AACR.
Genetic Variability of Smoking Persistence in African Americans
Authors: Hamidovic Ajna , Kasberger John L. , Young Taylor R. , Goodloe Robert J. , Redline Susan , Buxbaum Sarah G. , Benowitz Neal L. , Bergen Andrew W. , Butler Kenneth R. , Franceschini Nora , Gharib Sina A. , Hitsman Brian , Levy Daniel , Meng Yan , Papanicolaou George J. , Preis Sarah R. , Spring Bonnie , Styn Mindi A. , Tong Elisa K. , White Wendy B. , Wiggins Kerri L. , Jorgenson Eric
Published: March 2011

To date, most genetic association analyses of smoking behaviors have been conducted in populations of European ancestry and many of these studies focused on the phenotype that measures smoking quantity, that is, cigarettes per day. Additional association studies in diverse populations with different linkage disequilibrium patterns and an alternate phenotype, such as total tobacco exposure which accounts for intermittent periods of smoking cessation within a larger smoking period as measured in large cardiovascular risk studies, can aid the search for variants relevant to smoking behavior. For these reasons, we undertook an association analysis by using a genotyping array that includes 2,100 genes to analyze smoking persistence in unrelated African American participants from the Atherosclerosis Risk in Communities study. A locus located approximately 4 kb downstream from the 3′-UTR of the brain-derived neurotrophic factor (BDNF) significantly influenced smoking persistence. In addition, independent variants rs12915366 and rs12914385 in the cluster of genes encoding nicotinic acetylcholine receptor subunits (CHRNA5–CHRNA3–CHRNB4) on 15q25.1 were also associated with the phenotype in this sample of African American subjects. To our knowledge, this is the first study to more extensively evaluate the genome in the African American population, as a limited number of previous studies of smoking behavior in this population included evaluations of only single genomic regions. Cancer Prev Res; 4(5); 729–34. ©2011 AACR.
Selection of a Patient Subgroup with Advanced Esophageal Squamous Carcinoma Who Could Benefit from Second-Line Chemotherapy
Authors: Kim Seung Tae , Park Kyong Hwa , Oh Sang Cheul , Seo Jae Hong , Shin Sang Won , Kim Jun Suk , Kim Yeul Hong
Published: March 2011

Despite first-line therapy, most patients with advanced esophageal squamous cell carcinoma (ESCC) experience disease progression and may become eligible for second-line chemotherapy. Although commonly used, the role of salvage chemotherapy in patients with recurrent or metastatic ESCC has not yet been established. We analyzed 53 patients who had received second-line chemotherapy after the failure of cisplatin-based combination chemotherapy with or without radiotherapy as first-line therapy in ESCC between March 2000 and June 2008. Median progression-free survival (PFS) and overall survival (OS) for second-line chemotherapy were 2.4 and 5.2 months, respectively, with an overall response rate of 18.9%. In multivariate analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or more and PFS under first-line therapy <4 months were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: 0 = good; 1 = intermediate, and 2 = poor. The median OS for the good, intermediate, and poor prognostic groups were 11.2, 4.5 and 4.3 months, respectively (p < 0.001). The good prognostic group showed better OS than the intermediate or poor groups (p < 0.001). Second-line chemotherapy may be beneficial for OS in ESCC patients with ECOG PS 0–1 and PFS under first-line therapy ≧4 months.
Dual Effects of Hyperprolactinemia on Carrageenan-Induced Inflammatory Paw Edema in Rats
Authors: Ochoa-Amaya Julieta E. , Malucelli Benjamin E. , Cruz-Casallas Pablo E. , Nasello Antonia G. , Felicio Luciano F. , Carvalho-Freitas Maria I.R.
Published: March 2011

Objectives: The effects of short-term 5-day and long-term 30-day hyperprolactinemia induced by domperidone (1.7 mg/kg/day, s.c.) or ectopic pituitary graft on the acute inflammatory response induced by carrageenan were evaluated in male rats. Both models of hyperprolactinemia effectively increased serum prolactin (PRL) levels. Methods: The volume in milliliters of inflammatory edema was measured by plethysmography 1, 2, 3, 4, 6, 8 and 24 h after carrageenan injection. The areas under the inflammatory time-response curves were compared. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. Results: In both domperidone-treated and pituitary graft-implanted animals, short-term 5-day hyperprolactinemia increased the inflammatory response, while long-term 30-day hyperprolactinemia had anti-inflammatory effects. Body weight was not affected by either short- or long-term hyperprolactinemia. Conclusion: These results show that PRL has biphasic effects on the carrageenan-induced inflammatory response.
Potentials and Limits of Plasticity Induced by Working Memory Training in Old-Old Age
Authors: Zinke Katharina , Zeintl Melanie , Eschen Anne , Herzog Carole , Kliegel Matthias
Published: March 2011

Background: Old-old age (80+ years) is associated with substantial cognitive decline. In this population, training-induced cognitive plasticity has rarely been studied. While earlier findings on strategy trainings suggested reduced training gains in old-old age, recent results of an extensive process-based working memory (WM) training have been more positive. Objective: Following up on previous research, the present study aimed at examining the effects of a short WM training in old-old adults and the influence of baseline WM capacity on training gains. Methods: A training group (mean age: 86.8 years) and a matched control group (mean age: 87.1 years) participated in the study. The WM training consisted of five tasks that were trained in each of 10 sessions. To evaluate possible transfer effects, executive functions were assessed with two tests before and after training. The training group was divided via median split in high- and low-capacity individuals to determine the influence of baseline WM capacity on training gains. Results: The training group improved in four of the trained tasks (medium-to-large effects). Training gains were significantly larger in the training group than in the control group in only two of those tasks. The training effects were mainly driven by the low-capacity individuals who improved in all trained tasks. No transfer effects were observed. Conclusions: These positive effects of a short WM training, particularly for low-capacity individuals, emphasize the potential for cognitive plasticity in old-old age. The absence of transfer effects may also point to its limits.
Prevención de la carencia de hierro en la lactancia, la infancia y la adolescencia
Authors: Andersson Maria , Hurrell Richard F.
Published: March 2011

La carencia de hierro (CH) es frecuente en lactantes, niños y adolescentes de todo el mundo debido a sus elevadas necesidades de hierro durante el crecimiento, la precaria ingestión de hierro alimentario y la dieta con biodisponibilidad baja. El estado de hierro deficitario se asocia a consecuencias adversas para la salud durante toda la infancia. Las medidas preventivas deben iniciarse precozmente, y entre ellas destacan el aporte complementario de hierro en mujeres gestantes, el retraso en el pinzamiento del cordón umbilical en el parto y la alimentación exclusiva con leche materna durante 6 meses. El hierro tiene que incrementarse considerablemente después de los 4 a 6 primeros meses de vida y el contenido elevado en hierro de los alimentos complementarios es crucial. Aunque el enriquecimiento con hierro de las leches para lactantes y los cereales para lactantes, la adición de polvos de micronutrientes en alimentos complementarios de preparación casera o el suministro de gotas de hierro son las estrategias preventivas más eficaces en lactantes destetados, la introducción temprana de carne y el retraso en la introducción de leche de vaca son también importantes. Las estrategias preventivas en niños mayores implican abordajes alimentarios que aumenten el contenido y la biodisponibilidad del hierro en la alimentación, así como el consumo de alimentos enriquecidos con hierro. En zonas de CH extensa puede ser necesario el aporte complementario de hierro. Si el paludismo es frecuente sólo deben administrarse dosis elevadas de aportes complementarios en niños con CH confirmada. Todas las intervenciones para el control de la CH pediátrica deben integrarse en programas sanitarios nacionales y globales más extensos destinados a mujeres gestantes y niños, incluyendo la educación sanitaria, la prevención del paludismo y la desparasitación. Debe monitorizarse el impacto de las estrategias preventivas de la CH sobre el estado de hierro y la frecuencia de la CH midiendo periódicamente el estado de hierro en la población.
Changes in Skin and Subcutaneous Perfusion in Very-Low-Birth-Weight Infants during the Transitional Period
Authors: Ishiguro Akio , Sekine Takashi , Suzuki Keiji , Kurishima Clara , Ezaki Shoichi , Kunikata Tetsuya , Sobajima Hisanori , Tamura Masanori
Published: March 2011

Background: Conventional parameters of circulation that are routinely used in neonatal intensive care units, including blood pressure, have been reported to be inadequate in improving prognosis of very-low-birth-weight (VLBW) infants. Recently, the importance of evaluating the blood flow to each organ, including both vital and nonvital organs, has been increasingly recognized. Objectives: To study the changes in peripheral perfusion occurring in VLBW infants of less than 32 weeks’ gestation during the extrauterine transitional period. Methods: In 32 VLBW infants of less than 32 weeks’ gestation, forehead blood flow (FBF) and lower-limb blood flow (LBF) were measured for 48 h after birth using a novel laser Doppler flowmeter, and the indices of vascular resistance were estimated. Superior vena cava (SVC) blood flow was measured by echocardiography. Changes in these variables of circulation as well as the correlations were evaluated. Results: Both FBF and LBF significantly increased at 24 h, while the SVC flow remained unchanged over the same period. Both forehead and lower-limb vascular resistance indices significantly decreased at 24 h. LBF was negatively and positively correlated with estimated upper body vascular resistance and SVC flow, respectively. Conclusions: The increase in the peripheral blood flow along with the decrease in the peripheral vascular resistance indices, without an increase in the systemic blood flow at 24 h of age, indicated vasodilation in skin and subcutaneous tissue during the transitional period in VLBW infants. FBF and LBF can be useful parameters as indicators of both peripheral and systemic circulation.
Public Perspectives Regarding Data-Sharing Practices in Genomics Research
Authors: Haga S.B. , O’Daniel J.
Published: March 2011

Background: Genomics research data are often widely shared through a variety of mechanisms including publication, meetings and online databases. Re-identification of research participants from sequence data has been shown possible, raising concerns of participants’ privacy. Methods: In 2008–09, we convened 10 focus groups in Durham, N.C. to explore attitudes about how genomic research data were shared amongst the research community, communication of these practices to participants and how different policies might influence participants’ likelihood to consent to a genetic/genomic study. Focus groups were audio-recorded and transcripts were complemented by a short anonymous survey. Of 100 participants, 73% were female and 76% African-American, with a median age of 40–49 years. Results: Overall, we found that discussants expressed concerns about privacy and confidentially of data shared through online databases. Although discussants recognized the benefits of data-sharing, they believed it was important to inform research participants of a study’s data-sharing plans during the informed consent process. Discussants were significantly more likely to participate in a study that planned to deposit data in a restricted access online database compared to an open access database (p < 0.00001). Conclusions: The combination of the potential loss of privacy with concerns about data access and identity of the research sponsor warrants disclosure about a study’s data-sharing plans during the informed consent process.
ISSFAL 2010 Dinner Debate: Healthy Fats for Healthy Hearts – Annotated Report of a Scientific Discussion
Authors: Nettleton Joyce A. , Koletzko Berthold , Hornstra Gerard
Published: March 2011

Background/Aims: The importance of reducing saturated fatty acid intake to prevent cardiovascular disease and recommended intakes for omega-6 polyunsaturated fatty acids (PUFAs) are controversial. Therefore, experts debated these topics at the biennial meeting of the International Society for the Study of Fatty Acids and Lipids (ISSFAL), in May 2010. Methods: Debate transcripts, debaters’ and discussants’ reviews and literature citations were the basis of this report. Results:Participants agreed that saturates per se are not ‘bad’, but that dietary recommendations should emphasize the substitution of unsaturates for part of the saturates. Evidence supporting omega-6 PUFA intakes of 5 to 10% is mixed; some interpret the overall data from diverse studies as consistent with a reduction in the risk of cardiovascular mortality and events. Others assert that randomized controlled trial data suggest that higher intakes of omega-6 PUFAs are not associated with lower risk of heart disease, or may even increase it. Conclusions: All agreed that a 5-year randomized controlled trial comparing the effects of historically low (2%) with currently high (7.5%) linoleic acid intakes on cardiac endpoints would address the knowledge gap about the effects of different omega-6 PUFA intakes on the risk of heart disease.
Validity of the Quantitative EEG Statistical Pattern Recognition Method in Diagnosing Alzheimer’s Disease
Authors: Ommundsen Nina , Engedal Knut , Øksengård Anne Rita
Published: March 2011

Aims: To evaluate the use of quantitative EEG (qEEG) statistical pattern recognition in diagnosing Alzheimer’s disease (AD). Methods: qEEG was performed on 104 patients referred to a memory clinic. The qEEG results were compared to the clinical diagnosis made without access to the EEG results. Results: Of 30 patients with a clinical diagnosis of AD, 22 were test positive. Of the 74 patients without AD, 34 were test negative. The qEEG result was found to correlate with atrophy of the medial temporal lobe demonstrated on cerebral MRI (p = 0.002) and with scores on neuropsychological tests. Conclusion: The qEEG was poor at diagnosing AD, as it produced many false-positive results.
Illness Perceptions Predict Survival in Haemodialysis Patients
Authors: Chilcot Joseph , Wellsted David , Farrington Ken
Published: March 2011

Background: Illness perceptions have been shown to be important determinants of functional and psychosocial outcomes, including quality of life and treatment adherence in end-stage renal disease patients. The aim of this prospective study was to determine whether haemodialysis patients’ illness perceptions impact upon survival. Methods: Haemodialysis patients from a UK renal service completed the Revised Illness Perception Questionnaire. Over the study period (May 2007 to December 2010), all-cause mortality was recorded as the endpoint. Results: 223 patients were followed up for a median of 15.9 months (min. 10 days, max. 42.7 months). The median dialysis vintage was 17.6 months (min. 4 days, max. 391.3 months). Treatment control perceptions demonstrated a significant association with mortality (HR = 0.91, 95% CI: 0.83–0.99, p = 0.03). After controlling for covariates, including age, albumin, extra renal comorbidity and depression scores, perception of treatment control remained a significant predictor of mortality (HR = 0.89, 95% CI: 0.80–0.99, p = 0.03). Conclusions: Patients’ perceptions of treatment control (dialysis therapy) predict survival independently of survival risk factors, including comorbidity. Studies are required to test whether psychological interventions designed to modify maladaptive illness perceptions influence clinical outcomes in this patient setting.
Peri-operative management of antiplatelet therapy in patients with coronary artery disease
Authors: Cattaneo Marco , Chassot Pierre-Guy , Eichinger Sabine , Heymann Christian von , Hofmann Niklaus , Rickli Hans , Spannagl Michael , Ziegler Bernhard , Verheugt Freek , Huber Kurt , Korte Wolfgang
Published: March 2011

An increasing number of patients suffering from cardiovascular disease, especially coronary artery disease (CAD), are treated with aspirin and/or clopidogrel for the prevention of major adverse events. Unfortunately, there are no specific, widely accepted recommendations for the perioperative management of patients receiving antiplatelet therapy. Therefore, members of the Perioperative Haemostasis Group of the Society on Thrombosis and Haemostasis Research (GTH), the Perioperative Coagulation Group of the Austrian Society for Anesthesiology, Reanimation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society of Cardiology (ESC) have created this consensus position paper to provide clear recommendations on the perioperative use of antiplatelet agents (specifically with semi-urgent and urgent surgery), strongly supporting a multidisciplinary approach to optimize the treatment of individual patients with coronary artery disease who need major cardiac and non-cardiac surgery. With planned surgery, drug eluting stents (DES) should not be used unless surgery can be delayed for ≥12 months after DES implantation. If surgery cannot be delayed, surgical revascularisation, bare-metal stents or pure balloon angioplasty should be considered. During ongoing antiplatelet therapy, elective surgery should be delayed for the recommended duration of treatment. In patients with semi-urgent surgery, the decision to prematurely stop one or both antiplatelet agents (at least 5 days pre-operatively) has to be taken after multidisciplinary consultation, evaluating the individual thrombotic and bleeding risk. Urgently needed surgery has to take place under full antiplatelet therapy despite the increased bleeding risk. A multidisciplinary approach for optimal antithrombotic and haemostatic patient management is thus mandatory.
Pharmacokinetic evaluation of an oral tablet form of low-molecular-weight heparin and deoxycholic acid conjugate as a novel oral anticoagulant
Authors: Park Jin Woo , Jeon Ok Cheol , Kim Sang Kyoon , Al-Hilal Taslim , Lim Kyung-Min , Moon Hyun Tae , Kim Choong Yong , Byun Youngro
Published: March 2011

This study was designed to develop a solid oral dosage form of deoxycholic acid (DOCA)-conjugated low-molecular-weight heparin (LMWH) and to evaluate its oral absorption, distribution, and metabolic stability for the prospect of providing an orally bioavailable LMWH. The LMWH derivative (LHD) was synthesised and then formulated with solubilisers and other pharmaceutical excipients to form a solid tablet. Its absorption and distribution after oral administration were evaluated in mice, rats, and monkeys. The in vitro metabolic stability of LHD was examined by liver microsome assays. More than 80% of LHD was released from the tablet within 60 minutes, guaranteeing rapid tablet disintegration after oral administration. Oral bioavailability of LHD in mice, rats and monkeys were 16.1 ± 3.0, 15.6 ± 6.1, and 15.8 ± 2.5%, respectively. After the oral administration of 131I-tyramine-LHD, most of the absorbed drug remained in the blood circulation and was eliminated mainly through the kidneys. LHD was hardly metabolised by the liver microsomes and showed a stable metabolic pattern similar to that of LMWH. In a rat thrombosis model, 10 mg/kg of orally administered LHD reduced thrombus formation by 60.8%, which was comparable to the antithrombotic effect of the subcutaneously injected LMWH (100 IU/ kg). Solid tablets of LHD exhibited high oral absorption and statistically significant therapeutic effects in preventing venous thromboembolism. Accordingly, LHD tablets are expected to satisfy the unmet medical need for an oral heparin-based anticoagulant as an alternative to injectable heparin and oral warfarin.
Activation of Aryl Hydrocarbon Receptor Induces Vascular Inflammation and Promotes Atherosclerosis in Apolipoprotein E−/− Mice
Authors: Wu Dalei , Nishimura Noriko , Kuo Victoria , Fiehn Oliver , Shahbaz Sevini , Van Winkle Laura , Matsumura Fumio , Vogel Christoph Franz Adam
Published: March 2011

Objective—

Exposure to dioxins has been shown to contribute to the development of inflammatory diseases, such as atherosclerosis. Macrophage-mediated inflammation is a critical event in the initiation of atherosclerosis. Previously, we showed that treatment of macrophages with 2,3,7,8-tetrachlorodibenzo-
p
-dioxin (TCDD) leads to aryl hydrocarbon receptor (AhR)–dependent activation of inflammatory mediators and the formation of cholesterol-laden foam cells. However, the mechanisms responsible for the formation of atherosclerotic lesions mediated through AhR have not been identified.

Methods and Results—

An in vitro macrophage and an apolipoprotein E (ApoE)−/− mouse model were used to determine whether chemokines and their receptors are responsible for the AhR-mediated atherogenesis. Exposure of ApoE−/− mice to TCDD caused a time-dependent progression of atherosclerosis, which was associated with induction of inflammatory genes, including interleukin-8, as well as F4/80 and matrix metalloproteinase-12. A high-fat diet enhanced the TCDD-mediated inflammatory response and aggravated the formation of complex atheromas. Treatment with a CXCR2 inhibitor and an AhR antagonist reduced the TCDD-induced progression of early atherosclerotic lesions in ApoE−/− mice.

Conclusion—

The results suggest that CXCR2 mediates the atherogenic activity of environmental pollutants, such as dioxins, and contributes to the development of atherosclerosis through the induction of a vascular inflammatory response by activating the AhR-signaling pathway.
Peroxisome Proliferator-Activated Receptor-α Activation Promotes Macrophage Reverse Cholesterol Transport Through a Liver X Receptor–Dependent Pathway
Authors: Nakaya Kazuhiro , Tohyama Junichiro , Naik Snehal U. , Tanigawa Hiroyuki , MacPhee Colin , Billheimer Jeffrey T. , Rader Daniel J.
Published: March 2011

Objective—

Peroxisome proliferator-activated receptor-α (PPARα) activation has been shown in vitro to increase macrophage cholesterol efflux, the initial step in reverse cholesterol transport (RCT). However, it remains unclear whether PPARα activation promotes macrophage RCT in vivo.

Methods and Results—

We demonstrated that a specific potent PPARα agonist GW7647 inhibited atherosclerosis and promoted macrophage RCT in hypercholesterolemic mice expressing the human apolipoprotein A-I (apoA-I) gene. We compared the effect of GW7647 on RCT in human apoA-I transgenic (hA-ITg) mice with wild-type mice and showed that the PPARα agonist promoted RCT in hA-ITg mice to a much greater extent than in wild-type mice, indicating that human apoA-I expression is important for PPARα-induced RCT. We further investigated the dependence of the macrophage PPARα–liver X receptor (LXR) pathway on the promotion of RCT by GW7647. Primary murine macrophages lacking PPARα or LXR abolished the ability of GW7647 to promote RCT in hA-ITg mice. In concert, the PPARα agonist promoted cholesterol efflux and ATP binding cassette transporter A1/G1 expression in primary macrophages, and this was also by the PPARα-LXR pathway.

Conclusion—

Our observations demonstrate that a potent PPARα agonist promotes macrophage RCT in vivo in a manner that is enhanced by human apoA-I expression and dependent on both macrophage PPARα and LXR expression.
A Novel Lead Configuration for Optimal Spatio-Temporal Detection of Intracardiac Repolarization Alternans
Authors: Weiss Eric H. , Merchant Faisal M. , d'Avila Andre , Foley Lori , Reddy Vivek Y. , Singh Jagmeet P. , Mela Theofanie , Ruskin Jeremy N. , Armoundas Antonis A.
Published: March 2011

Background—

Electric alternans is a pattern of variation in the shape of ECG waveform that occurs every other beat. In humans, alternation in ventricular repolarization, known as repolarization alternans (RA), has been associated with increased vulnerability to ventricular tachycardia/fibrillation and sudden cardiac death.

Methods and Results—

This study investigates the spatio-temporal variability of intracardiac RA and its relationship to body surface RA in an acute myocardial ischemia model in swine. We developed a real-time multichannel repolarization signal acquisition, display, and analysis system to record ECG signals from catheters in the right ventricle, coronary sinus, left ventricle, and epicardial surface before and after circumflex coronary artery balloon occlusion. We found that RA is detectable within 4 minutes after the onset ischemia and is most prominently seen during the first half of the repolarization interval. Ischemia-induced RA was detectable on unipolar and bipolar leads (both in near- and far-field configurations) and on body surface leads. Far-field bipolar intracardiac leads were more sensitive for RA detection than body surface leads, with the probability of body surface RA detection increasing as the number of intracardiac leads detecting RA increased, approaching 100% when at least three intracardiac leads detected RA. We developed a novel, clinically applicable intracardiac lead system based on a triangular arrangement of leads spanning the right ventricular and coronary sinus catheters, which provided the highest sensitivity for intracardiac RA detection when compared with any other far-field bipolar sensing configurations.

Conclusions—

In conclusion, intracardiac alternans, a complex spatio-temporal phenomenon associated with arrhythmia susceptibility and sudden cardiac death, can be reliably detected through a novel triangular right ventricular–coronary sinus lead configuration.
Orai1 and CRAC Channel Dependence of VEGF-Activated Ca
2+
Entry and Endothelial Tube Formation
Authors: Li Jing , Cubbon Richard M. , Wilson Lesley A. , Amer Mohamed S. , McKeown Lynn , Hou Bing , Majeed Yasser , Tumova Sarka , Seymour Victoria A.L. , Taylor Hilary , Stacey Martin , O'Regan David , Foster Richard , Porter Karen E. , Kearney Mark T. , Beech David J.
Published: March 2011

Rationale:

Orai1 and the associated calcium release-activated calcium (CRAC) channel were discovered in the immune system. Existence also in endothelial cells has been suggested, but the relevance to endothelial biology is mostly unknown.

Objective:

The aim of this study was to investigate the relevance of Orai1 and CRAC channels to vascular endothelial growth factor (VEGF) and endothelial tube formation.

Methods and Results:

In human umbilical vein endothelial cells, Orai1 disruption by short-interfering RNA or dominant-negative mutant Orai1 inhibited calcium release–activated (store-operated) calcium entry, VEGF-evoked calcium entry, cell migration, and in vitro tube formation. Expression of exogenous wild-type Orai1 rescued the tube formation. VEGF receptor-2 and Orai1 partially colocalized. Orai1 disruption also inhibited calcium entry and tube formation in endothelial progenitor cells from human blood. A known blocker of the immune cell CRAC channel (3-fluoropyridine-4-carboxylic acid (2′,5′-dimethoxybiphenyl-4-yl)amide) was a strong blocker of store-operated calcium entry in endothelial cells and inhibited calcium entry evoked by VEGF in 3 types of human endothelial cell. The compound lacked effect on VEGF-evoked calcium-release, STIM1 clustering, and 2 types of transient receptor potential channels, TRPC6 and TRPV4. Without effect on cell viability, the compound inhibited human endothelial cell migration and tube formation in vitro and suppressed angiogenesis in vivo in the chick chorioallantoic membrane. The compound showed 100-fold greater potency for endothelial compared with immune cell calcium entry.

Conclusions:

The data suggest positive roles for Orai1 and CRAC channels in VEGF-evoked calcium entry and new opportunity for chemical modulation of angiogenesis.
Serotonin Transporter Gene Polymorphism in Chinese Patients With Poststroke Depression
Authors: Fang Jing , Yan Weihong , Jiang Guo-Xin , Li Wei , Cheng Qi
Published: March 2011

Background and Purpose—

We sought to compare the distribution of the serotonin transporter gene SLC6A4 polymorphism between depressed and nondepressed poststroke patients.

Methods—

Patients with cerebral stroke admitted to hospital during a 1-year period were enrolled in a 1:1 case-control study. All cases and controls were genotyped for polymorphism of the serotonin transporter-linked promoter region and the single-nucleotide polymorphism rs25531.

Results—

Among 367 patients with cerebral stroke, 57 (15.5%) were diagnosed with poststroke depression at 1 month after stroke. In the patients with poststroke depression, 7 genotypes of the serotonin transporter gene SLC6A4 were detected, and the frequency of
S/S
homozygotes was significantly higher (
P
=0.049) than that in controls.

Conclusions—

S/S
homozygosity may be positively associated with the occurrence of poststroke depression in Chinese patients.
A Consensus on Stroke
Authors: Fisher Rebecca J. , Gaynor Catherine , Kerr Micky , Langhorne Peter , Anderson Craig , Bautz-Holter Erik , Indredavik Bent , Mayo Nancy E. , Power Michael , Rodgers Helen , Rønning Ole Morten , Widén Holmqvist Lotta , Wolfe Charles D.A. , Walker Marion F.
Published: March 2011

Background and Purpose—

Research evidence supporting Early Supported Discharge (ESD) services has been summarized in a Cochrane Systematic Review. Trials have shown that ESD can reduce long-term dependency and admission to institutional care and reduce the length of hospital stay. No adverse impact on the mood or well-being of patients or carers has been reported. With the implementation of many national and international stroke initiatives, we felt it timely to reach consensus about ESD among trialists who contributed to the review.

Methods—

We used a modified Delphi approach with 10 ESD trialists. An agreed list of statements about ESD was generated from the Cochrane review and three rounds of consultation completed. ESD trialists rated statements regarding team composition, model of team work, intervention, and success.

Results—

Consensus of opinion (>75% agreement) was obtained on 47 of the 56 statements. Multidisciplinary, specialist stroke ESD teams should plan and co-ordinate both discharge from hospital and provide rehabilitation in the community. Specific eligibility criteria (safety, practicality, medical stability, and disability) need to be followed to ensure this service is provided for mild to moderate stroke patients who can benefit from ESD. Length of stay in hospital, patient and carer outcome measures and cost, need to be routinely audited.

Conclusions—

We have created a consensus document that can be used by commissioners and service providers in implementing ESD services. Our aim is to promote the use of recommendations derived from research findings to facilitate successful implementation of stroke services nationally and internationally.
Are Stroke Biomarkers Seeing Brain Vessels in Patients With Ischemic Stroke?
Authors: Kim Suk Jae , Choe Yeon Hyeon , Bang Oh Young ,   for the CHAOS-BIOMARKER Collaborators
Published: March 2011

Background and Purpose—

The significance of asymptomatic coronary artery atherosclerosis burden (CAB) in the interpretation of stroke biomarker results is unknown. We investigated biomarker values to determine if they are related to cerebral atherosclerosis with consideration of CAB.

Methods—

We prospectively recruited patients with noncardioembolic ischemic cerebrovascular disease who had no history of coronary artery disease. Patient-based vascular assessment was conducted using MRA for the cerebral arteries and cardiac CT angiography for the coronary arteries. Biomarkers including the C-reactive protein and homocysteine were measured.

Results—

A total of 178 patients were included in the study. The extracranial carotid stenosis was associated with the highest quartile of C-reactive protein (OR, 2.24; 95% CI, 1.04–4.55), whereas age was the only predictor of the highest quartile of homocysteine (OR, 1.06; 95% CI, 1.02–1.11). However, with consideration of CAB, CAB (≥2 segments with ≥50% stenosis) remained the only independent predictor for the highest quartile of C-reactive protein (OR, 8.69; 95% CI, 2.41–31.30) and homocysteine (OR, 11.44; 95% CI, 2.61–50.11).

Conclusions—

Our data emphasize the importance of CAB in biomarker studies of patients with ischemic stroke.
Bilingual Co-Training for Sentiment Classification of Chinese Product Reviews
Authors: Wan Xiaojun
Published: March 2011

The lack of reliable Chinese sentiment resources limits research progress on Chinese sentiment classification. However, there are many freely available English sentiment resources on the Web. This article focuses on the problem of cross-lingual sentiment classification, which leverages only available English resources for Chinese sentiment classification. We first investigate several basic methods (including lexicon-based methods and corpus-based methods) for cross-lingual sentiment classification by simply leveraging machine translation services to eliminate the language gap, and then propose a bilingual co-training approach to make use of both the English view and the Chinese view based on additional unlabeled Chinese data. Experimental results on two test sets show the effectiveness of the proposed approach, which can outperform basic methods and transductive methods.
South Africans and Mexicans in Florida: Intergroup Conflict
Authors: Mambou Elie
Published: March 2011

Newly arriving immigrants from Southern Africa and Mexicans do not get on well in the sunbelt state of Florida. A persistent theme emerging from discussions with South Africans on their relationship with Mexicans is that both sides perceive the other as culturally ethnocentric. The antagonistic relationship between both social groups is due to strong ethnic bonds and the clash of cultures.
Different Groups, Different Threats: A Multi-Threat Approach to the Experience of Stereotype Threats
Authors: Shapiro Jenessa R.
Published: March 2011

Two studies demonstrated that different negatively stereotyped groups are at risk for distinct forms of stereotype threats. The Multi-Threat Framework articulates six distinct stereotype threats and the unique constellations of variables (e.g., group identification, stereotype endorsement) that elicit each stereotype threat. Previous research suggests that different negatively stereotyped groups systematically vary across these stereotype threat elicitors; a pilot study confirms these differences. Across two studies, groups that tend to elicit low stereotype endorsement (religion, race/ethnicity, congenital blindness) were less likely to report experiencing self-as-source stereotype threats (stereotype threats requiring stereotype endorsement) and groups that tend to elicit low group identification (mental illness, obesity, blindness later in life) were less likely to report experiencing group-as-target stereotype threats (stereotype threats requiring group identification). This research suggests that traditional models may overlook the experiences of stereotype threats within some groups and that interventions tailored to address differences between stereotype threats will be most effective.
Community and resistance in Heidegger, Nancy and Agamben
Authors: Elliott Brian
Published: March 2011

Over the last two decades the work of Jean-Luc Nancy and Giorgio Agamben has attracted widespread attention both within philosophy and more broadly across the human sciences. Central to the thinking of Nancy and Agamben is a shared theory of community that offers a model of resistance to oppressive power through radical passivity. This article argues that this model inherits the inadequacies of Martin Heidegger’s attempts to conceptualize society and history. More specifically, Heidegger’s understanding of collective history in terms of ‘destiny’ implicitly regulates the figure of community proposed by Nancy and Agamben. This alignment with the Heideggerian notion of destiny means that these later thinkers fail to offer a credible model of resistance in terms of concretely determined means of productive counter-practices. As a consequence the usefulness of the thinking of Nancy and Agamben as a conceptual framework for emancipatory politics is at best extremely limited.
Legislative organization in MMP
Authors: Nemoto Kuniaki , Pekkanen Robert , Krauss Ellis S. , Roberts Nigel S.
Published: March 2011

How do electoral systems affect legislative organization? The change in electoral systems from Single Member District plurality (SMD) to Mixed Member Proportional (MMP) in New Zealand can illuminate how electoral incentives affect the distribution of cabinet positions. Because in SMD the outcome of individual local districts determines the number of seats a party wins collectively, New Zealand parties deploy cabinet posts in order to shore up the electoral fortunes of individual members. In MMP, the total number of seats a party receives is determined by the votes in the proportional representation (PR) portion for the party, which eliminates the incentives to reward electorally unsafe members with cabinet positions. We show that strong cabinet members, measured through experience as prior terms in the cabinet position, are still likely to be retained.
Use of Maraviroc-, Raltegravir-, and Etravirine-Containing Regimens in Treatment-Experienced Patients: A Case-Series Study
Authors: Youngblood Caleb , Sayana Shilpa , Khanlou Homayoon
Published: March 2011

The development of newer agents such as raltegravir, etravirine and maraviroc has improved the perspective of viral load suppression. However, there is not enough data regarding their use together. In this study, we describe nine patients who were triple-class experienced and were on a salvage regimen consisting of a combination of raltegravir, etravirine, and maraviroc. Our results showed that this regimen is safe with no major side effect and has good virological efficacy with two-thirds of the patients achieving an undetectable viral load by 24 weeks.
Arriba: effects of an educational intervention on prescribing behaviour in prevention of CVD in general practice
Authors: Keller Heidemarie , Krones Tanja , Becker Annette , Hirsch Oliver , Sönnichsen Andreas C , Popert Uwe , Kaufmann-Kolle Petra , Rochon Justine , Wegscheider Karl , Baum Erika , Donner-Banzhoff Norbert
Published: March 2011

Background: Evidence on the effectiveness of educational interventions on prescribing behaviour modification in prevention of cardiovascular disease is still insufficient. We evaluated the effects of a brief educational intervention on prescription of hydroxymethylglutaryl-CoA reductase inhibitors (statins), inhibitors of platelet aggregation (IPA), and antihypertensive agents (AH).

Design: Cluster randomised controlled trial with continuous medical education (CME) groups of general practitioners (GPs).

Methods: Prescription of statins, IPA, and AH were verified prior to study start (BL), immediately after index consultation (IC), and at follow-up after 6 months (FU). Prescription in patients at high risk (>15% risk of a cardiovascular event in 10 years, based on the Framingham equation) and no prescription in low-risk patients (≤ 15%) were considered appropriate.

Results: An intervention effect on prescribing could only be found for IPA. Generally, changes in prescription over time were all directed towards higher prescription rates and persisted to FU, independent of risk status and group allocation.

Conclusions: The active implementation of a brief evidence-based educational intervention on global risk in CVD did not lead directly to risk-adjusted changes in prescription. Investigations on an extended time scale would capture whether decision support of this kind would improve prescribing risk-adjusted sustainably.
Calcium: An Essential Mineral
Authors: Mackowiak Elaine D.
Published: March 2011

This review of calcium discusses briefly the role of the parathyroid glands, the gastrointestinal system, and the renal system in maintaining calcium homeostasis that is required for normal bone health, nerve and muscle function, and blood coagulation in the human body. The new recommendations for calcium intake by the United States Institute of Medicine are discussed. The concerns by the Institute of Medicine regarding adverse effects from excess calcium intake, especially hypercalcemia, nephrolithiasis (kidney stones), milk alkali syndrome, prostate cancer, and coronary heart disease, are reviewed.
The use of pure and impure placebo interventions in primary care - a qualitative approach
Authors: Fent Rahel , Rosemann Thomas , Fässler Margrit , Senn Oliver , Huber Carola A
Published: March 2011

Background

Placebos play an important role in clinical trials and several surveys have shown that they are also common in daily practice. Previous research focused primarily on the frequency of placebo use in outpatient care. Our aim was to explore physicians' views on the use of placebos in daily practice, whereby distinction was made between pure placebos (substances with no pharmacological effect, e.g. sugar pills) and impure placebos (substances with pharmacological effect but not on the condition being treated, e.g. antibiotics in viral infections or vitamins).

Methods

We performed semi-structured interviews with a sample of twelve primary care physicians (PCPs). The interview addressed individual definitions of a placebo, attitudes towards placebos and the participants' reasons for prescribing them. The interviews were transcribed and analysed using qualitative content analysis.

Results

The definition of a placebo given by the majority of the PCPs in our study was one which actually only describes pure placebos. This definition, combined with the fact that most impure placebos were not regarded as placebos at all, means that most of the participating PCPs were not aware of the extent to which placebos are used in daily practice. The PCPs stated that they use placebos (both pure and impure) mainly in the case of non-severe diseases for which there was often no satisfactory somatic explanation. According to the PCPs, cases like this are often treated by complementary and alternative therapies and these, too, are associated with placebo effects. However, all PCPs felt that the ethical aspects of such treatment were unclear and they were unsure as to how to communicate the use of placebos to their patients. Most of them would appreciate ethical guidelines on how to deal with this issue.

Conclusions

Many PCPs seem to be unaware that some of the drugs they prescribe are classified as impure placebos. Perceptions of effectiveness and doubts about the legal and ethical aspects of the use of placebos by PCPs may discourage their application. Dissemination of guidelines and consensus papers may be one approach, but it has to be acknowledged that the topic itself is in conflict with the PCPs' perception of themselves as professional and reliable physicians.
Mortality and morbidity among people living close to incinerators: a cohort study based on dispersion modeling for exposure assessment
Authors: Ranzi Andrea , Fano Valeria , Erspamer Laura , Lauriola Paolo , Perucci Carlo A , Forastiere Francesco
Published: March 2011

Background

Several studies have been conducted on the possible health effects for people living close to incinerators and well-conducted reviews are available. Nevertheless, several uncertainties limit the overall interpretation of the findings. We evaluated the health effects of emissions from two incinerators in a pilot cohort study.

Methods

The study area was defined as the 3.5 km radius around two incinerators located near Forlì (Italy). People who were residents in 1/1/1990, or subsequently became residents up to 31/12/2003, were enrolled in a longitudinal study (31,347 individuals). All the addresses were geocoded. Follow-up continued until 31/12/2003 by linking the mortality register, cancer registry and hospital admissions databases. Atmospheric Dispersion Model System (ADMS) software was used for exposure assessment; modelled concentration maps of heavy metals (annual average) were considered the indicators of exposure to atmospheric pollution from the incinerators, while concentration maps of nitrogen dioxide (NO2) were considered for exposure to other pollution sources. Age and area-based socioeconomic status adjusted rate ratios and 95% Confidence Intervals were estimated with Poisson regression, using the lowest exposure category to heavy metals as reference.

Results

The mortality and morbidity experience of the whole cohort did not differ from the regional population. In the internal analysis, no association between pollution exposure from the incinerators and all-cause and cause-specific mortality outcomes was observed in men, with the exception of colon cancer. Exposure to the incinerators was associated with cancer mortality among women, in particular for all cancer sites (RR for the highest exposure level = 1.47, 95% CI: 1.09, 1.99), stomach, colon, liver and breast cancer. No clear trend was detected for cancer incidence. No association was found for hospitalizations related to major diseases. NO2 levels, as a proxy from other pollution sources (traffic in particular), did not exert an important confounding role.

Conclusions

No increased risk of mortality and morbidity was found in the entire area. The internal analysis of the cohort based on dispersion modeling found excesses of mortality for some cancer types in the highest exposure categories, especially in women. The interpretation of the findings is limited given the pilot nature of the study.